Monthly Archives: May 2023

David Starkey says activists including Black Lives Matter are ‘trying to destroy white culture’ – Daily Mail

Posted: May 18, 2023 at 1:28 am

By Harry Howard, History Correspondent 13:11 17 May 2023, updated 15:15 17 May 2023

Historian David Starkey has sparked outrage after claiming that left-wing activists are trying to destroy 'white culture' and are 'jealous' of the Holocaust.

In a speech to the National Conservatism Conference in London, Dr Starkey claimed that groups such as Black Lives Matter were attempting to 'do exactly what was done to German culture because of Nazism and the Holocaust'.

He added: 'The determination is to replace the Holocaust with slavery.

'In other words, this is why Jews are under such attack from the Left. There's jealousy, fundamentally. There is jealousy of the moral primacy of the Holocaust and a determination to replace it with slavery.'

Reacting to his speech, former Labour MP John Mann, the Government's adviser on anti-Semitism, branded the academic 'pathetic' and said he was using the 'Jewish community and the Holocaust' to try to 'divide' people.

Dr Starkey, an expert on Tudor history, has previously been criticised for comments on slavery and the Black Lives Matter movement. He was accused of racism during coverage of the Coronation on GB News when he claimed that Rishi Sunak was 'not fully grounded in our culture'.

He later denied his comments were racist, saying he was referring to the Prime Minister being a 'typical international liberal' with no interest in British 'values'.

In 2020, he was dropped by his publisher and lost two university positions after claiming slavery was not genocide because there are 'so many damn blacks' in Africa and Britain.

In his speech to the National Conservatism Conference on Wednesday, Dr Starkey renewed his criticism of Black Lives Matter, denying that the movement cared about black lives at all.

To applause from the audience, he said: 'Movements like critical race theory and Black Lives Matter are not what they pretend to be.

'They are attempts at destroying the entire legitimacy of the Western political and cultural tradition.

'The idea that they are there to defend black lives is a preposterous notion.

'They do not care about black lives, they only care about the symbolic destruction of white culture. We have to be absolutely clear about this.'

He added: 'The narrative of Black Lives Matter is that Western culture and Anglo-American culture in particular are fundamentally morally defective, they are characterised by the mark of Cain and their strategy is to do exactly what was done to German culture because of Nazism and the Holocaust.'

During the conference's morning session, the audience also heard from Nigel Biggar, a professor emeritus of theology at the University of Oxford, who argued that the British Empire had a 'mixed' moral record and denied there was any reason to pay reparations to former colonies.

He said: 'As a Christian, Burkean conservative I don't expect perfection in any human affairs.

'Those who rule, just like those who are ruled, are creatures and sinners, finite and flawed.

'Even as I recognise the duty to repent and improve, I expect even the noblest of human efforts to be marred by limited power, moral obtuseness and culpable failure.

'And so I fear, indeed I loathe, the unforgiving, inhumane impatience of utopian perfectionists, whether they are Maoists or agents of Islamic State or progressive twittering social justice warriors.'

He added: 'Much of what our forebears achieved was extraordinary. We need to remember it, we need to admire it, we need to conserve it, and we need to build on it.'

Professor Biggar, the author of recent book Colonialism: A Moral Reckoning, also criticised Scottish nationalism as based on a false 'Braveheart' version of history.

He said: 'When too many Scots, in my view, align themselves with Scottish independence they do it, most of them, not because they've analysed policies.

'They do it in large part because they inhabit imaginatively a vision of the past that is false, a Braveheart past that excites unjustified nationalist indignation and resentment against the English and against Britain today.'

Other speakers at the National Conservatism Conference this week have included Home Secretary Suella Braverman and Levelling Up Secretary Michael Gove.

Former Business Secretary Jacob Rees Mogg had his speech interrupted on Monday by an Extinction Rebellion protestor.

The man, dressed in a shirt, tie and blazer, joined Mr Rees-Mogg at the lectern and told the audience: 'Ladies and gentlemen, you all look very nice people and I'm sure you are fantastically nice people.

'But I would like to draw your attention to a few characteristics of fascism.'

Read the rest here:

David Starkey says activists including Black Lives Matter are 'trying to destroy white culture' - Daily Mail

Posted in Black Lives Matter | Comments Off

I’m a Couples Therapist. Something New Is Happening in … – The New York Times

Posted: at 1:28 am

Questions of guilt hovered over another couple I worked with. He had recently cheated on his wife. They were generally deeply supportive of each other, but after she found out about his transgression, she was terribly upset and also confused. Their attempts to talk about what happened were halting. #MeToo rhetoric was woven into their discussions, functioning as a superego, shaping and inhibiting what they could even think. She said that she felt that the lessons of the movement were telling her not to forgive but to leave him Especially now, if a woman is being wronged, you get out. It was hard for her to know how she actually felt about it all. Early on, he couldnt separate remorse from fear. He was terrified of getting into trouble, and guiltiness prevailed. His voice was hushed while he scrutinized me intently, worried about how he would be perceived: There are a lot of men in this business right now who have taken positions of power and use them to have sex with people.

They were both white and understood their privilege and were apologetic about it. She often undid her own complaints I levitate out by having the thought, Oh, poor cis white woman. He was uncomfortable, too. He talked about reading the news about another Black or brown person being killed. And its just like I feel a little well, I feel guilty, to be honest, to be sitting here. The lessons of the Black Lives Matter movement initially can provoke such paralyzing guilt and shame that people become defensive and stop fully thinking. Yet over time, Ive found, the ideas can inspire deep psychological work, pushing people to reckon with the harm that has been done, the question of whom should be implicated, and the difference between virtue signaling and deeper concerns. These are tough and important lessons that can carry over into intimate relationships. In this case, the husband described a new understanding about the ways he exercised power at work: Hold on. Have I been an ally? Has it just been optics? These insights extended even to his way of speaking about his transgression. He had been rationalizing his behavior by saying that his wife was not giving him the attention he needed. But moving beyond what the couple called optics, now he was asking himself for a more thorough accounting of what his cheating was really about, and how it affected his wife. He explained how lonely he was if she traveled; he felt left behind and discarded, a feeling deeply familiar to him from early childhood. Acknowledging his vulnerability was hard for him, but it opened up a series of honest conversations between them. I convinced myself she does not desire me, he said. Im not the popular guy. Im not the strong guy. He linked those feelings to insecurities he felt as a teenager, when he suffered chronic teasing from kids at school for being perceived as effeminate.

This new, nondefensive way of talking made it possible for her to understand how his transgression hit her where she felt most insecure, and he could see it, generating remorse and forgiveness between them. She described how it had become easier for both of them to check themselves for their impact on the other person, and quickly notice or apologize. In one session she said, smiling: You were a jerk to me yesterday, and then you apologized a couple hours later. You recognized that you took out your frustration there on me because I was an easy target. He realized that he stopped skimming over ways he caused others pain: I actually was just thinking therapy and the Black Lives Matter movement have made me keenly aware of the words that just came out of my mouth, and the understanding that she reacted adversely to that, instead of me just going, We move on, because thats awkward. Theres a need now to address it. He continued: Did I just upset you? What did I do to just upset you?

Couples work always goes back to the challenge of otherness. Differences can show up around philosophical questions like what is important to devote a life to, or whether it is ethical to have babies with a climate crisis looming; or it can be closer to home, like whether having a sexual fantasy about a person who is not your partner is acceptable; or even as seemingly trivial as the correct way to load a dishwasher. Whatever the issue, differences can become a point of crisis in the relationship. Immediately the question of who is right, who gets their way or who has a better handle on reality pops up. Narcissistic vulnerabilities about self-worth appear, which then trigger an impulse to devalue the other. Partners try to resolve such impasses by digging in and working hard to convince the other of their own position, becoming further polarized.

The challenge of otherness may be easiest to see when we think of racial differences. This was certainly true for James and Michelle. Michelle was a calm, gentle, somewhat reserved African American social worker, and James, at the time a police officer, was a slight, wiry white man whose face did not reveal much feeling. They came in with classic conflicts around division of labor and differing parenting styles, and then the pandemic hit. Quarantined, working remotely and home-schooling their 3-year-old son, they started fighting about Covid protocols. Michelle was aware of the way that Covid was devastating Black communities and wanted to be careful. James, along with his fellow police officers and his conservative parents, thought the concern was overblown. Discussion about how race shaped James and Michelles experiences and ideas routinely dead-ended. If Michelle tried to bring up the topic, James would insist, I dont see color, and say he didnt know what she was talking about. In our sessions, Michelle sounded hopeless: She wanted him to understand how traumatizing Covid had been for Black people. But she was frustrated by his inability to acknowledge real difference, as if everyone was the same race. Hes of the mind-set that I dont see color. She continued setting out his thinking: I dont want to hear what you have to say because thats not how I think. That point of view obviously angers me, she said. James would shrug, expressionless. Michelle was describing the infuriating experience of trying to break through a barrier: Her husband wasnt consciously aware that whiteness was a perspective that was constricting what he could imagine or comprehend.

Read the original:

I'm a Couples Therapist. Something New Is Happening in ... - The New York Times

Posted in Black Lives Matter | Comments Off

Countering organized violence in the United States – Brookings Institution

Posted: at 1:28 am

Chairman Bishop, Ranking Member Ivey, and members of this distinguished subcommittee, thank you for the opportunity to submit a statement for the record.1

Political violence in the United States is a grave threat not only to the lives of Americans, but also to the health of American democracy. Violence poses a threat to political leaders and to Americans who participate in politics. It polarizes our already-divided country and undermines political discourse.

Although this hearing focuses on left-wing violence and movements like Antifa, it is vital to recognize that in recent years violence linked to white supremacist, anti-government, and other causes lumped under the label right-wing have proven far more lethal and more politically consequential. Congress must use its powers to bolster law enforcement, improve our understanding of the threat, and otherwise fight the scourge of extremism. All political leaders must reject those who espouse violence and extremism, creating a clear line between legitimate politics and illegitimate extremism.

The remainder of this statement has three sections. I first provide some caveats on the labels used, as both right- and left- wing movements are divided, and the uses of terms are politicized. In the second section, I compare left-wing and right-wing political violence, noting in particular the grave danger that anti-government and white supremacist violence has posed in recent years. In the final section, I offer recommendations for reducing the threat of political violence in the United States.

Using the labels left-wing or right-wing to describe political violence invariably leads to the conflation, sometimes accidental and sometimes deliberate, of extremist activity with the actions of legitimate political activists. To be clear, the overwhelming majority of the millions of Americans who are concerned about police violence against minority communities and similar legitimate causes associated with the political left in the United States have nothing to do with the violent extreme; similarly, the overwhelming majority of the millions of Americans who favor strong gun rights, are concerned with federal government overreach, worry about the level of immigration, and otherwise share concerns associated with the political right have nothing to do with the violent extreme. We can, and should, have a robust debate with people espousing their views, even if unpopular, without the threat of violence. By using the labels left and right to describe violence extremists I am trying to separate out legitimate politics from illegitimate violence.

Making this more difficult, and in contrast to jihadist groups like Al Qaeda and the Islamic State (ISIS), both left- and especially right-wing extremists are difficult to categorize, with few robust organizations but strong informal networks. Antifa is a label under which left-wing extremism is often lumped. Contrary to much commentary, Antifa is not a group or an organization in any traditional sense; rather, it is a set of beliefs shared by a few activists, many of whom disagree with one another considerably. Antifa is short for anti-fascist (itself a word used broadly and inconsistently), and many of its members today focus on what they consider to be anti-racist activism. They do not have a tight organization or coherent command and control, and indeed the concept of hierarchy is anathema to many local groups. In a few cities, their ranks are slightly coherent, but in most places, it is a small group of informal activists. Much of the information put out about Antifa, including by prominent figures such as President Donald Trump, has exaggerated its coherence and reach.2 Russian influence operations have also attempted to amplify disinformation linked to Antifa.3

Many Antifa adherents do not favor violence of any sort. Others argue it is necessary to be prepared for violence in self-defense. Some of these attend rallies, such as those protesting police brutality, prepared to defend protesters against groups like the Proud Boys. They are prepared, indeed at times eager, to brawl with them. Others Doxx their opponents, publishing embarrassing private information (usually on their neo-Nazi or other right-wing extremist activities) to get them fired or shamed in their communities.4 A smaller number do use violence without even the excuse of self-defense, such as the Antifa adherents who joined broad, and mostly peaceful, anti-Trump or pro-Black Lives Matter protests and smashed the windows of local businesses or threw Molotov cocktails. In a very small but still notable number of cases, Antifa activists have used more lethal forms of violence. In July 2019, one activist attacked an Immigration and Customs Enforcement detention center in Tacoma, Washington with a rifle and bombs. As this spectrum of activity related to violence suggests, using the label Antifa thus tells us little about the specifics of an adherents goals or methods.

This organizational chaos is even more pronounced among right-wing extremists. Some are anti-immigrant, some focus on the Black community, and many are anti-Semitic and anti-Muslim. Some hate all these communities. Others are strongly opposed to the federal government to the point that they see government officials as agents of tyranny. Making this more complex, many among these extremists embrace a range of conspiracy theories, and some embrace a virulent form of male supremacy. Organized groups themselves are weak: almost every major attack involving right-wing terrorism in the United States was conducted by individuals with little or no group involvement so-called Lone Wolf attacks.5 An important exception to this was the January 6, 2021, insurrection, in which violent groups like the Proud Boys and Oath Keepers played leading roles, although even there the majority of participants were not affiliated with these extremist groups.6

There are different ways to measure the danger posed by political extremists, but one of the simplest is to look at the number of people they kill. In the post-9/11 era, on the left, the United States has seen one murder, which occurred when Michael Forest Reinoeh, a left-wing extremist, shot and killed a member of the right-wing extremist organization Patriot Prayer in Portland in 2020. The killer had previously provided security for left-wing protests. He described himself as anti-fascist, but he was not a member of any local Antifa group.

Numbers for right-wing extremist violence are far higher, with numerous high-profile terrorist attacks as well as lower-level assaults, vandalism, and other forms of violence. Since the 9/11 terrorist attacks, far-right extremists have killed 130 people in the United States, more than any other political cause, including jihadists.7 Notable attacks in recent years include the 2018 Pittsburgh Synagogue attack, the 2019 El Paso mall killings, and the 2022 Buffalo market attack. A range of far-right extremists, including organized groups such as the Proud Boys and Oath Keepers as well as hundreds of unaffiliated conspiracy theorists, anti-government extremists, and ordinary supporters of President Trump, also stormed the U.S. Capitol on January 6, 2021, in a direct assault on American democracy. Far-right extremist violence has not abated: earlier this month, on May 6, 2023, an apparent neo-Nazi with misogynist leanings shot up a Texas mall, killing eight people.

Another concern is the role of right-wing extremism in the ranks of the military and among police officers. Although the overwhelming majority of law enforcement and military personnel reject extremism, even small numbers of extremists in uniform are of concern given the important role these entities play in American society, including their position at the frontline of the battle against violent extremism itself. Here the difference with left-wing extremism is considerable: many left-wing adherents reject authority, see the police and military as instruments of authoritarianism, and otherwise are far less likely to join their ranks. Many right-wing extremists, in contrast, glorify military and police forces in theory, though in practice they have attacked them. Violent extremist crimes among those with U.S. military backgrounds have increased significantly in the last decade, and such members have played important roles in anti-government extremist groups like the Oath Keepers and disorganized anti-government movements like the Boogaloos.8

In contrast to far-right extremists in the past, todays violent far-right often targets law enforcement. On January 6, 2021, of course, far-right extremists were responsible for the death of a Capitol police officer and the wounding of over 100 others. A right-wing extremist also threatened an FBI facility in Cincinnati in 2021.9 Anti-government extremists have regularly attacked and killed local police, questioned their authority to enforce the law, resisted arrest, and otherwise pose a grave threat to law enforcement.

Another danger of violence is that it infects and degrades politics. After the 9/11 attacks, Americans of all political beliefs came together, supporting a strong response to jihadist terrorism. Unfortunately, during its four years in office, the Trump administration increased public fears of white supremacist and anti-government violence because of its perceived toleration, and at times even encouragement, of these causes. Trumps rhetoric matched some white supremacist talking points, playing down police violence against Black people, calling Mexican immigrants rapists, declaring COVID-19 to be a Chinese virus, telling Black and other minority members of Congress to go back to their home countries, claiming a mythical deep state, and demonizing the FBI. When violence occurred, as it did during a 2017 Unite the Right rally in Charlottesville, Virginia organized by white supremacists, Trump opined that their ranks included very fine people.

Political support, or at least toleration, of extremism also occurs at the state and local level: political figures have at times embraced racist and anti-government ideas, and a few even have ties to violent organizations.10 The demonization of the FBI when it carries out legitimate investigations of American politicians is another instance of how politics can degrade an effective response against extremism. At times, the effects are simply to turn good Americans off politics, with many who would otherwise engage in local politics afraid of, or simply disgusted by, the constant stream of abuse from extremists.

Extremism of one political variety encourages its opposite. Antifa, in fact, rose in both its appeal and its activism with the rise of the white nationalist alt-right early in the Trump administration.11 Similarly, many right-wing extremists claim they are acting in self-defense, often promoting outlandish conspiracy theories to prove that Antifa and others are controlling events and thus justifying their violence.

The U.S. government, including the U.S. Congress, should take several steps to fight political extremism of all stripes.

A first step is to understand the problem beyond isolated examples. Data on extremism is bad in the United States, and Congress should require and resource better reporting at the federal, state, and local levels. Despite attempts such as the 1990 Hate Crimes Statistics Act, many local jurisdictions, including many that have troubling histories, simply do not report on hate crimes, and those that do report often are inconsistent.12 Legislation that required consistent reporting and resourced local jurisdictions would improve our understanding of violent extremism and allow a better distribution of resources. The FBI and the Department of Homeland Security should use this data to produce regular reports on the threat of extremism in the United States.

Ensuring the ranks of U.S. law enforcement and the U.S. military remain free from violent extremism of any sort is also vital. This requires careful screening of recruits, training that helps inoculate them against extremist recruitment, and other measures that reduce the danger to ensure that those charged with protecting America do so fairly and impartially.

Existing laws offer law enforcement many ways to disrupt violent extremist activities. On social media, many openly threaten others in specific terms and otherwise reveal their intentions. Many extremists violate state gun laws and rules against private paramilitary militias.13 Congress should encourage federal, state, and local officials to use their authorities to target those entities that have a propensity toward violence.

Both right-wing and left-wing extremists use social media to publicize their messages and to harass their enemies. Online harassment is especially common against people of color and women, making their lives far more difficult and discouraging many from engaging in political discourse. Social media companies should be strongly encouraged to crack down on such harassment.

Political leaders should also work to delegitimize violent extremists of all stripes, drawing clear lines between those engaging in politics even on contentious issues such as abortion, immigration, gun rights, and police abuse and those who favor or legitimate violence. Leaders should disavow any connections to those who espouse violence against minorities, law enforcement, and others. A model is President George H.W. Bush, who declared neo-Nazi and former KKK leader David Duke a charlatan and called for him to be rejected by voters when Duke ran as the Republican candidate for governor of Louisiana in 1991.14 Such condemnations are the right thing to do. They also discourage extremists from trying to take over the political process and ensure that U.S. law enforcement agencies know they can use the proper power of the law against violent extremists without political criticism.

Strong leadership is necessary in the fight against extremism. It is my hope that hearings such as these can both identify weaknesses that must be corrected and also educate the public on the need to stop political violence of any sort.

See the original post here:

Countering organized violence in the United States - Brookings Institution

Posted in Black Lives Matter | Comments Off

It’s Time for Call of Duty to Return to One Fictional War – GameRant

Posted: at 1:28 am

It's clear why the Call of Duty franchise has remained popular for as long as it has, with the frequent releases of the IP exploring a huge range of settings and delivering different gameplay experiences to fans. Despite being considered by many as the best first-person shooter franchise, there's still room for it to innovate on some of its ideas.

One of the largest factors of any Call of Duty title is the conflict that the game chooses to focus on, with this being the decision that largely informs the narrative of an installment or the feel of its multiplayer modes. The CoD franchise has famously explored a huge range of different wars over the years, but one stands out as one of the most fascinating and tense. When considering the plethora of the franchise's modern settings, it may be time for World War 3 to come back into the fold.

RELATED: Call of Duty: Modern Warfare 2 Update Makes It Completely Unplayable for Some PC Gamers

Call of Duty veterans will be familiar with the franchise's roots, in which the IP exclusively focused on portraying the Second World War for some time. Fans would understandably grow tired of this after a while, and in response, the franchise began to explore more modern and futuristic settings, with one such setting being a third World War.

This iconic portrayal of World War 3 came within the first Modern Warfare trilogy, and was focused on heavily in Modern Warfare 3. Telling the tale of Task Force 141, the original Modern Warfare trilogy portrayed some of the most hard-hitting and memorable sequences across the entire franchise, and this was largely due to the stakes of its World War 3 setting. While this particular conflict was covered quite extensively in the original trilogy, it would be fascinating to see how such a devastating conflict could be portrayed on modern hardware. With this in mind, the current reboot of the Modern Warfare trilogy fosters the perfect environment for a return to World War 3, priding itself on its gripping detail while of course possessing some of the same narrative beats of the original trilogy.

The Call of Duty franchise recently found success in its Modern Warfare reboot, with Infinity Ward telling a different tale in the MW universe, involving many of the same beloved characters from the original trilogy. Modern Warfare 2's recent release forwarded this new narrative and set up the franchise for a potentially explosive finale in its more-than-likely follow-up installment.

While the new Modern Warfare series does well to portray previous franchise characters in fresh lights, it is hard not to notice that the stakes of its overarching narrative currently feel much smaller than the originals. With that being said, the third installment to the original MW trilogy was arguably the most high-octane, and there is no reason that the upcoming Modern Warfare 3 cannot also take this narrative direction. The original MW3 was the title that portrayed World War 3 in the most horrific and memorable detail, giving further credence to how the new trilogy's third installment is the perfect opportunity to re-explore the conflict. That version of WW3 was also sparked by the No Russian incident, the same terrorist attack that Makarov carries out within the post credits scene from the new Modern Warfare 2, so it would only make sense for World War 3 to occur again in the new timeline.

As more than a decade has passed since the franchise's last portrayal of WW3, it is clear to see the appeal of revisiting the conflict with the more detailed and dynamic capabilities of modern hardware. While also crucially upping the ante of what the next Modern Warfare installment's narrative will involve, the potential success that a revived World War 3 setting could bring for Call of Duty is backed by the franchise's very own track record.

MORE: Call of Duty: Modern Warfare 2 Can Kill Two Birds With One Stone By Adding this Operator

More here:

It's Time for Call of Duty to Return to One Fictional War - GameRant

Posted in Ww3 | Comments Off

Are killer robots the future of war? – Al Jazeera English

Posted: at 1:28 am

Humanity stands on the brink of a new era of warfare.

Driven by rapid developments in artificial intelligence, weapons platforms that can identify, target and decide to kill human beings on their own without an officer directing an attack or a soldier pulling the trigger are fast transforming the future of conflict.

Officially, they are called lethal autonomous weapons systems (LAWS), but critics call them killer robots. Many countries, including the United States, China, the United Kingdom, India, Iran, Israel, South Korea, Russia and Turkey, have invested heavily in developing such weapons in recent years.

A United Nations report suggests that Turkish-made Kargu-2 drones in fully-automatic mode marked the dawn of this new age when they attacked combatants in Libya in 2020 amid that countrys ongoing conflict.

Autonomous drones have also played a crucial role in the war in Ukraine, where both Moscow and Kyiv have deployed these uncrewed weapons to target enemy soldiers and infrastructure.

The emergence and deployment of such machines are driving intense debates among experts, activists and diplomats worldwide as they grapple with the possible benefits and potential risks of using robots, and consider whether and how to stop them.

Yet in an increasingly divided geopolitical landscape, can the international community arrive at any consensus on these machines? Do the ethical, legal and technological threats posed by such weapons make it essential to stop them before they take over the battlefield? Is a blanket ban feasible, or is a set of regulations a more realistic option? Al Jazeera posed these questions to leading experts in the field.

The short answer: An outright blanket ban on autonomous weapon systems does not look likely anytime soon. However, a growing chorus of voices especially from the Global South is calling for their regulation, and experts believe a global taboo of the kind that is in place against the use of chemical weapons is possible. Major military powers may be intrigued by the potential battlefield advantages such systems could give them, but there seems to be little appetite for them outside governments and generals.

In late March, Yasmin Afina, research associate at the London-based Chatham House, described to the House of Lords, the second chamber of the UK parliament, how the US National Security Agency (NSA) had once mistakenly identified an Al Jazeera journalist as an al-Qaeda courier. That labelling which also resulted in the journalist being put on a US watch list only came to light through documents leaked in 2013 by Edward Snowden, a former contractor with the NSA.

A surveillance system of the kind behind that incident is not in itself a weapon system, but it is lethality-enabling, Afina said in her deposition. If you were to engage the target, the journalist, that would absolutely be against international humanitarian law considerations.

The potential for LAWS to trigger a chain reaction of escalatory events worries Toby Walsh, an AI expert at the University of New South Wales in Sydney, Australia.

We know what happens when we put complex computer systems against each other in an uncertain and competitive environment. Its called the stock market, wrote Walsh in written evidence submitted to the House of Lords.

The only way to stop dangerous feedback loops and undesirable outcomes is to use circuit breakers. On the stock market, we can simply unwind transactions when such a situation occurs. But we cannot unwind the start of WW3, he added.

That does not mean researchers should stop developing the technology behind automatic weapons systems, Walsh told Al Jazeera. That technology, he said, could bring benefits in other fields.

For example, the same algorithms used in car safety systems that avoid collisions with pedestrians will be the algorithms that go into your autonomous drone that identify combatants, track them and its just a sign change to kill them as opposed to avoid them, he said. It would be morally wrong to deny the world a chance to reduce road deaths, he argued.

Instead, the answer might lie in emulating the relatively successful regulation of chemical weapons, Walsh said.

When chemical weapons are used, they make front-page headlines and trigger a global outcry. The UNs Chemical Weapons Convention prohibits their development, production, stockpiling and use. That, combined with international taboos around chemical weapons, has also successfully stopped major arms companies from producing them.

We cant put Pandora back into a box, but those measures seem to have largely limited the misuse of chemical weapons in the battlefields around the world today, Walsh said.

To be sure, AI-driven autonomous weapons systems have their benefits from a military perspective.

They could carry out some battlefield tasks without the use of soldiers thus reducing the risk of casualties. Supporters argue that sophisticated technology embedded in these systems could eliminate or reduce human error in decision-making and eliminate biases. Greater accuracy in targeting could, at least in theory, reduce accidental human casualties.

Autonomous weapons systems can also be deployed for defensive capabilities, with lightning-fast detection algorithms able to detect and eliminate a potential threat with greater efficiency and accuracy than humans.

Yet to many experts and rights groups, the risks of these LAWs outweigh any potential advantages ranging from the possibility of technical malfunctions with no oversight to violations of international law and the ethical concerns over emotionless machines making decisions of life and death.

Central to all of those concerns is the question of accountability.

In 2019, the 126 counties party to the United Nations Convention on Certain Conventional Weapons (CCW) agreed upon 11 guiding principles recommended by a group of experts appointed by the UN to address concerns about autonomous weapons.

Among those principles was a decision that international humanitarian law would fully apply to the potential development of such weapons. But experts say it is unclear how that principle will be applied in the fog of war. If a robot commits a war crime, for instance, would it be the commanding officer in charge of the theatre of conflict who would be considered responsible? Or would the buck stop at higher-ups who decided to deploy the machine in the first place? Would the manufacturer of the weapon be liable?

All of this represents a major gap in policy conversation on the subject, Stockholm International Peace Research Institute (SIPRI) researchers Vincent Boulanin and Marta Bo wrote in an article in March.

There is not even an official or internationally agreed definition for autonomous weapons systems, Boulanin told Al Jazeera, though most countries agree that the critical element is that the system will be able to identify, select and engage the target without human intervention.

According to Boulanin, the director of the Governance of Artificial Intelligence Programme at SIPRI, weapons systems already operational today fit this description. One such example is the US-made MIM-104 Patriot surface-to-air missile system currently used by many countries, including Saudi Arabia and Israel.

We are talking about a capability, a function that can be used across very different types of weapons systems, that can come in all shapes and forms and can be used in very different types of missions, said Boulanin.

So if you were to ban something, he explained, you would have to narrow down exactly the type of weapon or scenario that you find particularly problematic.

Rather than a blanket ban, a two-tier set of regulations would be a more realistic outcome, he said, with some weapons systems prohibited and others allowed if they meet a strict set of requirements.

The million dollar question now is, basically, what are the elements that would fit into these two buckets? Boulanin said.

It is a question that different states have yet to agree on.

There is an even more fundamental division among nations over how to approach the question of autonomous weapons: Should the world seek a legally binding set of rules or merely a political declaration of intent?

A political declaration can take many forms but would likely include a public statement where major powers would state their common position on the subject and promise to adhere to the principle points laid out in the document. This could look like the joint statement issued by China, Russia, the UK, the US and France on preventing nuclear war and avoiding arms races signed in January 2022, in which they affirmed, among other things, that a nuclear war can never be won and must never be fought.

Boulanin said it is a question that nations have radically different views on. Russia has been very open about its objections to legally binding instruments; the UK and US are also critical, viewing it as premature and seeking a political declaration as a first step, he said.

Some others, like China and India, have been more ambiguous.

China has supported a ban on the use of fully autonomous weapons but not on their development a position in keeping with the view that some of the worlds most dangerous military tools, including nuclear weapons, can serve as defensive deterrents.

Chinas domestic arms industry has duly pressed ahead with the development of such technology, including the Blowfish A2 drones, which can fly in swarms and independently engage a target. The classified 912 Project also aims to develop underwater robots over the next few years.

India, meanwhile, has expressed concerns about a new race for such machines widening the technology gulf between nations, and about the proliferation of killer robots including to non-state actors but has simultaneously doubled down on developing its own autonomous weapons systems.

Exactly how much resources militaries are committing to developing LAWS is difficult to gauge, but a 2021 Amnesty International report states that several major military powers were investing heavily in the development of autonomous systems. The UK, it said, was developing an uncrewed autonomous drone that could identify a target within a programmed area, while Russia has built a robot tank which can be fitted with a machine gun or grenade launcher.

Autonomous functions can also be added to existing or developing technologies, such as the US-made Switchblade 600 loitering missile.

The real pushback against such weapons systems is coming from large parts of the Global South especially Latin America, Africa and the Middle East that are seeking legally binding regulations.

Leading the campaign in recent times is a country that has shown that peace can be ensured without an army.

In February, Costa Ricas government, along with the local nongovernmental organisation FUNPADEM organised a regional conference attended by representatives from almost every country in Latin America and the Caribbean.

The conferences Beln Communiqu (PDF), which more than 30 states adopted, highlighted the dangers of autonomous weapons systems and called for the international community to respond to them by developing and strengthening the international legal framework.

This is our national position based on our cultural view of peace, Bradon Mata Aguilar, a project technician at FUNPADEM, told Al Jazeera.

Costa Ricas army was abolished in 1948, and it remains one of the most stable countries in the region. Aguilar explains that this fact creates a huge difference between how other states and Costa Rica look at implementing these legally binding instruments.

Costa Rica, he said, is seeking a complete prohibition of fully autonomous weapons and regulations implemented to control the use and development of semi-autonomous weapons.

Groups like the Stop Killer Robots (PDF) campaign, a coalition of nongovernmental organisations that seek to preemptively ban LAWS, and the International Committee of the Red Cross (ICRC) also had a strong presence at the conference in Costa Rica.

Then, on March 25, at the Ibero-American Summit in the Dominican Republic, 22 heads of state of Spanish- and Portuguese-speaking countries issued a joint statement (PDF), calling for the negotiation of a legally binding international instrument, with prohibitions and regulations regarding autonomy in weapons systems.

That sentiment was echoed two days later when the Central American Integration System groupings member states, including Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama, adopted a similar statement calling for urgent negotiations.

Multiple nations in Africa and the Middle East Algeria, Namibia, Ghana, Uganda, Zimbabwe, Morocco, Egypt, Jordan, Iraq and Palestine among them have called for a complete ban on fully autonomous weapons systems over the past decade. Others like South Africa have called for regulations but have stopped short of seeking a full ban.

All of this momentum shows that the appetite for legislation is there, said Walsh. Weve seen three dozen or more countries at the floor of the United Nations call for regulation. Weve seen the European Parliament vote for it. Weve seen the African Union vote for it.

But a key ingredient for the success of any talks is missing, according to some experts: trust.

Amid rising geopolitical tensions, many nations are worried about whether they can believe in what rivals state officially, analysts say.

That absence of trust plays out at two levels. Since international conventions like the CCW depend on consensus, it only takes one country to be disruptive to stop talks progressing, said Walsh.

But even if a new international law or set of regulations were to come into place, would they be effectively implemented? That is an open question because many nations are not playing by the rules-based order anymore, said Walsh.

Boulanin agrees with those concerns.

States can agree [thats] one thing, but compliance is another thing, Boulanin said.

I think some states are worried that if they were to agree on an ambitious regulatory framework, they would potentially shoot themselves in the foot, he added. If their adversaries did not play by the rules and developed LAWS, this would put them at a strategic disadvantage, he explained.

That risk, however, does not mean we shouldnt keep trying to agree on new norms for responsible behaviour, Boulanin said.

Already, one traditional worry that any international law would be unable to keep pace with the rapid rate at which technology is advancing has been addressed, he said, with the UNs approach now focusing on regulations that are technology-agnostic.

Still, there are even more basic issues at stake in this debate, including over the morality of machines taking peoples lives without any human being involved in the decision-making process.

The Martens Clause, which has formed a part of the laws of armed conflict since its first appearance in the preamble to the 1899 Hague Convention (II), is often used in discussions over the ethics of autonomous weapons systems. It declares that in the absence of specific treaty law on a topic, people are still protected by custom, the principles of humanity, and the dictates of public conscience.

In 2019, UN Secretary-General Antnio Guterres said machines with the power and discretion to take lives without human involvement were politically unacceptable and morally repugnant.

And many military personnel Walsh has spoken with for his research seem squeamish about fully autonomous weapons too.

He said that he has found almost universally that the lower down the ranks you go, the closer to the battlefield you get, there is more pushback against the idea that you could be fighting against robots.

Beyond laws, regulations and geopolitics, there is a more fundamental problem with the idea of machines lacking human empathy making such critical decisions, said Walsh.

Its disrespectful to human dignity.

See the article here:

Are killer robots the future of war? - Al Jazeera English

Posted in Ww3 | Comments Off

Tildrakizumab Linked With HRQOL Improvement in Psoriasis in a Real-World Setting – AJMC.com Managed Markets Network

Posted: at 1:28 am

Treatment with tildrakizumab improved health-related quality of life (HRQoL) and patient-reported symptoms in those with psoriasis in a real-world setting, according to a new study published in The Journal of Dermatological Treatment.

The antiinterleukin-23 p19 monoclonal antibody is approved for treatment of adults with moderate to severe plaque psoriasis.

Psoriasis and its symptoms, which can include itch, pain and scaling, have substantial negative effects on patients QOL. Previous research shows patients report negative effects on sleep and rest, limitations on daily activities, and disruption to social interactions. Many also experience depression, anxiety or addiction.

The chronic multisystem disease manifests most noticeably as skin inflammation, the study authors said. Plaque psoriasis, the most common form of the condition, often appears on the skin of the knees, elbows, scalp, buttocks and trunk.

Of all the symptoms of psoriasis, itch has been reported to contribute the most to reductions in patients emotional well-being, sleep, and daily activity.

However, in general, the relationship between clinical treatment of psoriasis and patients HRQoL is poorly understood and may be underestimated by clinicians, the researchers wrote. There is therefore an unmet need for greater understanding of this relationship to inform the choice of therapeutic intervention.

To address the knowledge gap, the investigators carried out a phase 4 study under real-world conditions. The current research outlines results after 28 weeks of treatment with tildrakizumab.

All participants received tildrakizumab 100mg at weeks 0 and 4, and every 12 weeks thereafter. The researchers measured progress via the Psychological General Well-Being Index (PGWBI), Dermatology Life Quality Index (DLQI), and Itch-, Pain-, and Scaling-Numerical Rating Scale scores. Of the 55 enrolled patients, 53 were evaluated at week 28.

Data showed:

Just over half of patients included were male and the majority were White. The mean patient age was 48.6 years.

Despites PGWBI score improvements seen for general health and positive well-being, no statistically significant improvements were seen from baseline to week 28 for anxiety, vitality, depressed mood, and self-control.

However, the treatment did result in improvements in reported itching, pain, and scaling beginning at week 4 and these were maintained throughout the study window.

Clinical trials have often focused on the effects of skin clearance on the HRQOL of patients with psoriasis. Complete skin clearance has been associated with higher scores on measures of HRQOL compared with almost complete clearance, the authors explained.

Previous research on theimpact of the efficacy of tildrakizumab treatment has shown absolute Psoriasis Area Severity Index scores correlated with DLQI total scores.

In controlled clinical trials, strict inclusion and exclusion criteria may preclude findings from fully representing or characterizing the patient population in real-world clinical practice, the researchers said.

To date, there has been little published real-world evidence regarding HRQOL in patients with moderate to severe plaque psoriasis treated with tildrakizumab, they added.

The relatively small sample size marks a limitation to the current study, and it remains unclear whether tildrakizumab treatment may affect patients HRQOL over a longer period of time.

Additional research is recommended to further guide clinicians in choosing optimal treatment strategies to improve HRQOL in patients with moderate to severe psoriasis, the authors concluded.

Reference

Bhatia N, Heim J, Schenkel B, Vasquez JG. Quality of life and patient-reported symptoms in a phase 4, real-world study of tildrakizumab in patients with moderate-to-severe psoriasis: week 28 interim analysis. J Dermatolog Treat. Published online May 11, 2023. doi:10.1080/09546634.2023.2200872

Posted in Psoriasis | Comments Off

Clinical Utility of Deucravacitinib for the Management of Moderate to … – Dove Medical Press

Posted: at 1:28 am

1School of Medicine, University of California at San Francisco, San Francisco, CA, USA; 2Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA

Correspondence: Joy Q Jin, Box 1212, Floor 01, Room 101, 2340 Sutter Street, San Francisco, CA, 94115, USA, Tel +1 415-353-7800, Fax +1 415-502-4126, Email [emailprotected]

Introduction: Psoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options.Objective: With the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis.Methods: A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis.Results: One placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97 18.48; 2=4.08, I2=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12 16. No cardiovascular events, serious infections, or lab abnormalities were noted.Conclusion: Deucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinibs superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

Keywords: apremilast, deucravacitinib, meta-analysis, placebo, plaque psoriasis, systematic review

Psoriasis is a chronic inflammatory disorder of the skin and joints that affects 8 million Americans and 23% of the population globally.1 Psoriasis has a profound impact on both the physical and psychosocial health of those affected. Patients are subject to increased risk of developing comorbid systemic disease, including cardiovascular disease, diabetes, anxiety, depression, and all-cause mortality.2

A variety of therapies are available for the treatment of psoriasis, including topical medications, phototherapy, oral and biologic agents. Oral immunosuppressants such as methotrexate and cyclosporine may be highly effective for some patients, but such treatments have significant potential for adverse effects.3 For individuals with a more severe psoriatic disease course, treatment with a systemic therapy such as a biologic agent is often required. Recent advancements surrounding new targeted agents have yielded promising results; here, we review the clinical potential of deucravacitinib (ie, BMS-986165, SotyktuTM), a new oral small molecule approved by the US Food and Drug Administration (FDA) in September 2022 for the treatment of moderate-to-severe psoriasis.

The pathogenesis of psoriasis is characterized by aberrant keratinocyte differentiation and excessive growth of the epidermis, leading to the formation of erythematous patches and plaques with thick overlying scale.4 Psoriasis pathogenesis involves a complex interplay of genetic (eg, susceptibility alleles) and environmental factors, which can combine to trigger systemic inflammatory cascades leading to disease presentation.4 While psoriatic immune dysregulation is complex and not fully elucidated, T helper 17 (Th17) cells are known to be a central component that, when aberrantly activated, produce important effector cytokines acting in a positive feedback loop to recruit additional immune cells and accelerate psoriasis development.5,6

Involvement of the interleukin (IL)-23/IL17 pathway mediates psoriasis via the activation and promotion of keratinocyte proliferation.5 Cytokines like TNF-, IL-17, and IL-23 are the targets of biologic agents used in psoriasis.7,8 Many of these same cytokines, including IL-23, bind to type I and II cytokine receptors, which possess no inherent catalytic activity and must rely on Janus kinase (JAK) proteins to mediate their effects.7 Tyrosine kinase 2 (TYK2) is one of four members of the JAK family of proteins.7

JAK/STAT signaling refers to a system comprised of a dimeric transmembrane cytokine receptor, a pair of intracellular JAKs, and a family of Signal Transducers and Activators of Transcription (STATs).7 Upon binding of a cytokine to its receptor, a conformational change in the receptor proteins occur, leading to autophosphorylation of intracellular JAKs.7 This enables another conformational change leading to the phosphorylation of STATs, which then dissociate from the receptor complex before translocating to the nucleus and acting as transcription factors.7

TYK2 pairs with other JAK family members to mediate the signaling of IL-12 and IL-23 receptors, as well as type I IFN receptors; TYK2 inhibition leads to reduced Th17 cell polarization, increased suppressive functions of regulatory T cells, and additional downstream effects protective against psoriasis development.912 Given TYK2s role downstream of current biologic targets such as IL-12 and IL-23, TYK2 inhibition may serve as a promising strategy that can address existing challenges in the treatment of moderate-to-severe psoriasis.12

In September 2022, deucravacitiniban oral, first-in-class, small molecule, selective allosteric inhibitor of TYK2was approved by the FDA for the treatment of psoriasis in the U.S.13 Deucravacitinib binds to the catalytically inactive pseudokinase regulatory domain of TYK2 and stabilizes an inhibitory interaction between the regulatory and catalytic domains.13 Through this method, TYK2 is inactivated and cannot interact with other receptors to lead to downstream signal transduction.11,14 In preclinical studies, deucravacitinib was revealed to inhibit TYK2 with high selectivity and minimal off-target effects on other JAK family members,11,14 suggesting that deucravacitinib may possess an improved safety profile compared to less specific JAK inhibitors, which have been associated with hyperlipidemia, increased risk of infections, and other systemic changes.1416

Given recent FDA-approval and promising clinical data, we aimed to investigate deucravacitinibs clinical utility for the treatment of moderate-to-severe psoriasis. To our knowledge, no systematic review has been conductedhere, we performed a systematic review with meta-analysis to synthesize the findings from randomized controlled trials (RCTs) studying deucravacitinib for psoriasis.

As a review, all data used were non-identifiable and publicly available; institutional review board approval was not required at the University of California, San Francisco. The study protocol and design are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2020 guidelines.17 A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in March 2023 using a combination of the terms (deucravacitinib OR sotyktu) AND (psoriasis).

The efficacy of new psoriasis treatments is measured in clinical trials via standardized, objective disease severity metrics, including the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA).18,19 These tools utilize grading scales to stratify disease severity based on clinical characteristics including body surface area involvement and degree of erythema, induration, and scaling. Given the impact psoriatic disease has on patients psychosocial health and quality of life, concomitant assessment of these domains with tools such as the Dermatology Life Quality Index (DLQI) is appropriate and often co-reported in clinical trials or post hoc studies.19

Studies included in this review were RCTs investigating human subjects with moderate-to-severe psoriasis (thus, only Phase II trials and above, as Phase I trials were conducted in healthy participants),20 defined in clinical trials as static PGA (sPGA) 3, PASI 12, and body surface area (BSA) 10%, treated with deucravacitinib. RCTs that studied psoriatic arthritis but not psoriasis were excluded.21 Study characteristics including clinical trial name/number, number of patients, intervention dose and frequency, treatment duration, clinical efficacy, and safety outcomes were obtained using a standardized table tailored to this review.

Initial screening of studies was performed manually by two independent reviewers (J.Q.J., R.K.S.). Any queries in eligibility criteria were resolved via adjudication by an additional reviewer (W.L.). Data abstraction was performed by two independent reviewers (J.Q.J., R.K.S.). All randomized studies included for analysis were assessed for risk of bias by two independent authors (J.Q.J., R.K.S.) using the Critical Appraisal Skills Programme (CASP) checklist for RCTs.22

Primary outcomes sought for the purpose of this review included an sPGA of 0 or 1 (indicating clear or almost clear disease). Secondary outcomes included an sPGA of 0, a 75%, 90%, or 100% improvement in the PASI score (ie, PASI 75, PASI 90, or PASI 100), a DLQI score of 0 or 1, scalp-specific PGA (ss-PGA) of 0 or 1, and a PGA of Fingernail Psoriasis (PGA-F) of 0 or 1. The final endpoint was determined to be Week 1216, as all included studies reported efficacy measures within this timepoint.

Meta-analysis was performed using the Cochrane Review Manager 5.4 application comparing the sPGA 0/1 rates of deucravacitinib versus placebo. Only data from patients receiving the FDA-approved dose of deucravacitinib (6 mg per day) or placebo were included for meta-analysis. An odds ratio (OR) was calculated using the Mantel-Haenszel fixed-effects method, which was chosen over the Peto method as the latter is better suited for rare event occurrences.23 Significance of heterogeneity was assessed using the 2 test (P<0.1 set as statistically significant) and presented as the I2 test (I2>50% indicates significant heterogeneity, I2<25% indicates non-significant heterogeneity).

Following the application of inclusion and exclusion criteria (PRISMA diagram shown in Figure 1), three RCTs were included for review, including one Phase II placebo-controlled trial (NCT02931838)24 and two Phase III placebo-controlled and active-comparator (apremilast) RCTs (POETYK PSO-1, POETYK PSO-2).25,26 The three RCTs were composed of a total of 1953 patients with moderate-to-severe psoriasisincluding 1065 treated with deucravacitinib, 422 treated with apremilast, and 466 who received placebo. Overall, deucravacitinib patients showed marked improvement in disease severity and quality-of-life outcomes compared to apremilast and placebo groups; deucravacitinib patients with scalp psoriasis demonstrated marked improvement compared to apremilast and placebo groups, but improvements in fingernail psoriasis measures were not significant (Table 1). The risk of bias assessment of all studies is presented in Table 2.

Table 1 Clinical Outcomes Reported in Deucravacitinib Randomized Controlled Trials for Moderate-to-Severe Psoriasis

Table 2 Risk-Bias Assessment of Included Studies

Figure 1 PRISMA diagram showing study selection.

NCT02931838 was a 12-week, randomized, placebo-controlled, dose-ranging Phase II clinical trial that included 267 adults with moderate-to-severe plaque psoriasis (sPGA 3, PASI 12, and BSA 10%; mean baseline PASI was 18).24 The primary clinical outcome assessed was PASI 75 at Week 12 compared to baseline. Patients were randomly assigned to one of six groups to receive placebo medication or deucravacitinib orally at the following frequencies: 3 mg every other day (QOD), 3 mg daily (QD), 3 mg twice daily (BID), 6 mg BID, or 12 mg QD. Detailed clinical outcomes can be found in Table 1; improvements in PASI scores were associated with higher doses of deucravacitinib and were improved compared to placebo groups. Nearly 70% of the cohort that received deucravacitinib 3 mg BID (closest to the FDA-approved dosage of 6 mg once daily) achieved PASI 75 at Week 12, compared to 6.7% of the placebo cohort. Improvements in clinical outcomes were correlated with biomarker changes and patient-reported quality-of-life (percent of patients who achieved DLQI 0/1).27

POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) were randomized, double-blind, double-dummy Phase III trials that compared the efficacy and safety of deucravacitinib versus an active-comparator (apremilast) and placebo.25,26 A total of 666 patients (PSO-1) and 1020 patients (PSO-2) were randomized 2:1:1 to deucravacitinib 6 mg QD, apremilast 30 mg BID, or placebo. All participants receiving placebo were crossed over to receive deucravacitinib at Week 16; patients receiving apremilast who did not achieve PASI 50 (PSO-1) or PASI 75 (PSO-2) by Week 16 were also switched to the deucravacitinib group. In PSO-2, deucravacitinib patients achieving PASI 75 at Week 24 were re-randomized 1:1 to deucravacitinib at the same dosing schedule or placebo for the remainder of the study. If the newly switched placebo patients exhibited disease relapse, they were re-started on deucravacitinib.

Detailed clinical outcomes for both studies are reported in Table 1; briefly, deucravacitinib was shown to be more effective than both comparator and placebo at Week 16 for both primary endpoints assessed (PASI 75 and sPGA 0/1). The percent of patients who achieved PASI 75 in PSO-1 and PSO-2 (vs apremilast, placebo) were 58.7% (vs 35.1%, 12.7%) and 53.6% (vs 40.2%, 9.4%), respectively. The percent of patients who achieved sPGA 0/1 in PSO-1 and PSO-2 (vs apremilast, placebo) were 53.6% (vs 32.1%, 7.2%) and 50.3% (34.3%, 8.6%), respectively.

In all included studies, deucravacitinib was well-tolerated, with similar percentages and types of adverse events (AEs) reported among patients treated with placebo or comparator drugs at Week 12 or 16.2426 The occurrence of any AE by Week 12 or 16 in NCT02931838, POETYK PSO-1, and POETYK PSO-2 were 64% (vs 51% in placebo group), 53.0% (vs 42.4% in placebo group, 55.4% in apremilast group), and 57.5% (vs 54.3% in placebo group, 59.1% in apremilast group), respectively. In all trials, the most frequently reported AEs associated with deucravacitinib were nasopharyngitis (6.311%) and upper respiratory tract infection (26.3%). Other common AEs reported in the POETYK trials included headache (4.34.8% vs 3.05.5% in placebo group vs 10.111.0% in apremilast group), diarrhea (3.94.7% vs 3.67.5% in placebo group vs 10.113.0% in apremilast group), and nausea (1.22.1% vs 1.42.4% in placebo group vs 9.111.3% in apremilast group), which occurred at similar frequencies to placebo and generally decreased frequencies compared to the apremilast treatment group. Across the three studies, no significant changes in mean blood counts (including neutrophil and platelet levels), serum lipids (including total cholesterol), creatinine, creatine phosphokinase, liver enzymes, or immunoglobulins were reported. Among all patients treated with deucravacitinib, no serious cases of herpes zoster leading to discontinuation occurred; additionally, no opportunistic infections or tuberculosis were reported.

Meta-analysis of the three placebo-controlled RCTs comparing the rates of clearance (sPGA 0/1) in patients with moderate-to-severe psoriasis (N = 1354; deucravacitinib, n = 888; placebo, n = 466) demonstrated superior efficacy of deucravacitinib compared to placebo (OR, 12.87; 95% confidence interval (CI), 8.9718.48) (Figure 2). Heterogeneity was determined as significant (2 = 4.08, I2 = 51%) (Figure 2).

Figure 2 Forest plot of deucravacitinib versus placebo in the treatment of moderate-to-severe psoriasis. The primary outcome assessed was achievement of static Physician Global Assessment (sPGA) 0 or 1 at Week 12 (NCT02931838) or Week 16 (POETYK trials) in deucravacitinib- versus placebo-treated patients.

Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel fixed-effects method.

Psoriasis is a systemic, immune dysregulatory condition that has a significant detrimental impact on a patients overall health and quality of life. While a range of biologic therapies are available for the treatment of more severe diseaseincluding agents that target TNF-, IL-12/IL-23, IL-17, and IL-23certain biologics can be contraindicated for individuals based on comorbid conditions, safety concerns, or insurance coverage issues. Furthermore, patients with more severe psoriasis are more likely to experience biologic failure, including the sequential failure of multiple biologics, despite adequate time attempting each agent.2830 Thus, there remains a need to develop new targeted therapeuticsparticularly those that can act via a different mechanism of action than existing systemic agentsto treat patients with moderate-to-severe psoriasis.

While the development of psoriasis is complex and involves an interplay between multiple immune signaling pathways, JAK/STAT signaling has been shown to hold a central dysregulatory role in psoriasis pathogenesis for years.16 The importance of such signaling in psoriasis was further emphasized after a recent study found methotrexate to inhibit the JAK/STAT pathway as a potential secondary mechanism of action, particularly relevant in psoriatic arthritis.31 Unfortunately, first-generation JAK inhibitors targeting JAK2 and JAK3 (eg, tofacitinib, baricitinib) experienced limited success for psoriasis as a disease indication due to safety concerns, despite effective associated clinical outcomes (eg, PASI reduction).32,33 For example, incidence of major adverse cardiovascular events and cancer were found to be higher in tofacitinib-treated groups in a dose-dependent fashion for rheumatoid arthritis patients.34 Thus, JAK inhibitors were previously approved only for psoriatic arthritis or for off-label use in certain psoriasis patients who had not responded to conventional systemic therapies.33

Deucravacitinib represents a major advancement as a first-in-class systemic therapy that differs from prior JAK inhibitors and other psoriasis biologics in several ways. First, deucravacitinib is a small molecule, meaning it can be administered by a variety of routes, including orallyas opposed to injected or infused, as many psoriasis biologics are.35 Because of deucravacitinibs oral bioavailability and simpler dosing regimens, adherence to the intended treatment plan may be easier to achieve for patients, and access to first-line therapy for moderate-to-severe psoriasis may be expanded due to lower drug costs.35 Additionally, small molecules may also hold a reduced risk of immunogenicity compared to biologics, which can translate to a longer period of efficacy in individual patients.35 Finally, our systematic review of RCTs found that psoriasis patients treated with deucravacitinib did not experience major AEs at rates significantly different from patients treated with apremilast or placebo.26,36 In our review of the three included RCTs, the most frequently reported AEs tended to occur at similar rates compared to the placebo group and at lower frequencies compared to apremilast treatment. None of the three included RCTs reported significant changes in blood count, cholesterol levels, or opportunistic infections among patients treated with deucravacitinib, which were all concerns that hampered the approval of JAK inhibitors for psoriasis treatment in the past.37,38 Taken together, these results suggest that deucravacitinib may have favorable safety features as a selective inhibitor of TYK2 in the JAK familyalthough results should be interpreted with caution due to the limited follow-up periods reported. Further head-to-head comparative studies should be conducted.

The meta-analysis conducted in our study is, to our knowledge, the first performed that compares plaque psoriasis patients treated with deucravacitinib versus placebo. The results (Figure 2) indicate that the primary endpoint of sPGA 0/1, a validated tool providing a global estimate of a patients psoriatic disease severity, was achieved significantly more frequently in deucravacitinib compared to placebo treatment groups.18 These promising results of clinical efficacy bode well for other TYK2 inhibitors in clinical development for psoriasis, including rapsacitinib, brepocitinib, NDI-034858, and ESK-001.33 Overall, our systematic review and meta-analysis found deucravacitinib to yield positive improvements for multiple efficacy endpoints, including clinical outcomes (eg, sPGA, PASI) and patient-reported quality of life (via DLQI).

Deucravacitinib is an effective, oral small molecule that possesses good efficacy and safety features, indicating its potential to serve as a first-line treatment for moderate-to-severe psoriasis. Patients with plaque psoriasis showed significant improvements in objective, disease-specific clinical parameters, with meta-analysis of Phase II and III RCTs demonstrating the superiority of deucravacitinib compared to placebo. Within individual RCTs, deucravacitinib was also found to yield increased rates of disease improvement and reduced AE incidence compared to apremilast. Thus, deucravacitinib achieved clinical efficacy while maintaining a favorable safety profilean important barrier to prior JAK inhibitor use in psoriasisconsistent with its unique mechanism of action and selectivity for TYK2. While further studies should be conducted to evaluate the long-term safety and efficacy of deucravacitinib and compare it to existing biologics, deucravacitinib holds promising clinical utility and represents an important step forward as a first-in-class treatment option for psoriasis patients.

AE, adverse event; BID, twice daily; CASP, Critical Appraisal Skills Programme; DLQI, Dermatology Life Quality Index; FDA, Food and Drug Administration; IL, interleukin; JAK, Janus kinase; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; PGA-F, PGA of Fingernail Psoriasis; QD, daily; QOD, every other day; RCT, randomized controlled trial; sPGA, static PGA; ss-PGA, scalp-specific PGA; STAT, Signal Transducers and Activators of Transcription; Th17, T helper 17; TYK, tyrosine kinase.

All data analyzed in this systematic review can be searched in publicly available databases including PubMed and Embase.

This is a review article of published studies; ethics approval was not required by our Institutional Review Board.

No identifiable patient information was included in this article.

We are thankful to all the reviewers who contributed to this article.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. Conception: JQJ, VR, WL. Methodology: all authors. Formal analysis and investigation: JQJ, RKS. Writingoriginal draft preparation: JQJ, RKS. Writingreview and editing: all authors. Supervision: WL.

This study was not funded.

J.Q.J. has received research grant funding from the National Psoriasis Foundation and institutional funding from the University of California, San Francisco. T.B. has received research grant funding from Novartis and Regeneron and is a principal investigator for trials sponsored by Abbvie, Castle, CorEvitas, Dermavant, Galderma, Mindera, and Pfizer. T.B. has also served as an advisor for Abbvie, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, Sun, and UCB. W.L. has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. The authors report no other conflicts of interest in this work.

1. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis prevalence in adults in the United States. JAMA Dermatol. 2021;157(8):940946. doi:10.1001/JAMADERMATOL.2021.2007

2. Yan D, Blauvelt A, Dey AK, et al. New frontiers in psoriatic disease research, part II: comorbidities and targeted therapies. J Invest Dermatol. 2021;141(10):23282337. doi:10.1016/J.JID.2021.02.743

3. Heydendael VM, Spuls PI, Opmeer BC, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349(7):658665. doi:10.1056/NEJMOA021359

4. Greb JE, Goldminz AM, Elder JT, et al. Psoriasis. Nat Rev Dis Prim. 2016;2. doi:10.1038/NRDP.2016.82

5. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020;323(19):19451960. doi:10.1001/JAMA.2020.4006

6. Rendon A, Schkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. doi:10.3390/IJMS20061475

7. Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002;285(12):124. doi:10.1016/S0378-1119(02)00398-0

8. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605. doi:10.4049/JIMMUNOL.1800013

9. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10. doi:10.3389/FIMMU.2019.02342

10. Muromoto R, Shimoda K, Oritani K, Matsuda T. Therapeutic advantage of Tyk2 inhibition for treating autoimmune and chronic inflammatory diseases. Biol Pharm Bull. 2021;44(11):15851592. doi:10.1248/BPB.B21-00609

11. Burke JR, Cheng L, Gillooly KM, et al. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci Transl Med. 2019;11:502. doi:10.1126/SCITRANSLMED.AAW1736

12. Abduelmula A, Gooderham MJ. TYK2 inhibition: changing the treatment landscape for psoriasis? Expert Review of Clinical Immunology. 2021;18(3):185187. doi:10.1080/1744666X.2022.2008240

13. Hoy SM. Deucravacitinib: first approval. Drugs. 2022;82(17):16711679. doi:10.1007/S40265-022-01796-Y

14. Chimalakonda A, Burke J, Cheng L, et al. Selectivity profile of the tyrosine kinase 2 inhibitor deucravacitinib compared with janus kinase 1/2/3 inhibitors. Dermatol Ther (Heidelb). 2021;11(5):17631776. doi:10.1007/S13555-021-00596-8

15. Gadina M, Chisolm DA, Philips RL, McInness IB, Changelian PS, OShea JJ. Translating JAKs to jakinibs. J Immunol. 2020;204(8):20112020. doi:10.4049/JIMMUNOL.1901477

16. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, OShea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843862. doi:10.1038/NRD.2017.201

17. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372. doi:10.1136/BMJ.N71

18. Robinson A, Kardos M, Kimball AB. Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis. J Am Acad Dermatol. 2012;66(3):369375. doi:10.1016/J.JAAD.2011.01.022

19. Mattei PL, Corey KC, Kimball AB. Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies. J Eur Acad Dermatol Venereol. 2014;28(3):333337. doi:10.1111/JDV.12106

20. Catlett IM, Aras U, Hansen L, et al. First-in-human study of deucravacitinib: a selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Clin Transl Sci. 2023;16(1):151164. doi:10.1111/CTS.13435

21. Mease PJ, Deodhar AA, Van Der Heijde D, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815822. doi:10.1136/ANNRHEUMDIS-2021-221664

22. CASP CHECKLISTS - CASP - critical appraisal skills programme. Available from: https://casp-uk.net/casp-tools-checklists/. Accessed September 21, 2022.

23. Cochrane Training. Chapter 10: analysing data and undertaking meta-analyses. Available from: https://training.cochrane.org/handbook/current/chapter-10. Accessed March 15, 2023.

24. Papp K, Gordon K, Thai D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):13131321. doi:10.1056/NEJMOA1806382/SUPPL_FILE/NEJMOA1806382_DATA-SHARING.PDF

25. Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled Phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88(1):2939. doi:10.1016/J.JAAD.2022.07.002

26. Strober B, Thai D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88(1):4051. doi:10.1016/J.JAAD.2022.08.061

27. Thai D, Strober B, Gordon KB, et al. Deucravacitinib in moderate to severe psoriasis: clinical and quality-of-life outcomes in a phase 2 trial. Dermatol Ther (Heidelb). 2022;12(2):495510. doi:10.1007/S13555-021-00649-Y

28. Mastorino L, Roccuzzo G, Dapavo P, et al. Patients with psoriasis resistant to multiple biological therapies: characteristics and definition of a difficult-to-treat population. Br J Dermatol. 2022;187(2):263265. doi:10.1111/BJD.21048

29. Hadeler E, Kumar S, Yeroushalmi S, et al. Factors associated with multi-biologic use in psoriasis patients at an academic medical center and review of biologic survival. J Psoriasis Psoriatic Arthritis. 2022. doi:10.1177/24755303221131259

30. Shalom G, Cohen AD, Ziv M, et al. Biologic drug survival in Israeli psoriasis patients. J Am Acad Dermatol. 2017;76(4):662669.e1. doi:10.1016/J.JAAD.2016.10.033

31. Gremese E, Alivernini S, Tolusso B, Zeidler MP, Ferraccioli G. JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy. J Leukoc Biol. 2019;106(5):10631068. doi:10.1002/JLB.5RU0519-145R

32. Jo CE, Gooderham M, Beecker J. TYK 2 inhibitors for the treatment of dermatologic conditions: the evolution of JAK inhibitors. Int J Dermatol. 2022;61(2):139147. doi:10.1111/IJD.15605

33. Loo WJ, Turchin I, Prajapati VH, et al. Clinical implications of targeting the JAK-STAT pathway in psoriatic disease: emphasis on the TYK2 pathway. J Cutan Med Surg. 2022. doi:10.1177/12034754221141680/ASSET/IMAGES/LARGE/10.1177_12034754221141680-FIG2.JPEG

34. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316326. doi:10.1056/NEJMOA2109927/SUPPL_FILE/NEJMOA2109927_DATA-SHARING.PDF

35. Makurvet FD. Biologics vs. small molecules: drug costs and patient access. Med Drug Discov. 2021;9:100075. doi:10.1016/J.MEDIDD.2020.100075

36. Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2022. doi:10.1016/J.JAAD.2022.07.002

37. Canada.ca. Health Canada safety review finds link between the use of Xeljanz and Xeljanz XR (tofacitinib) and increased risk of serious heart-related issues and cancer. Available from: https://recalls-rappels.canada.ca/en/alert-recall/health-canada-safety-review-finds-link-between-use-xeljanz-and-xeljanz-xr-tofacitinib. Accessed March 15, 2023.

38. FDA. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death. Accessed March 15, 2023.

Here is the original post:
Clinical Utility of Deucravacitinib for the Management of Moderate to ... - Dove Medical Press

Posted in Psoriasis | Comments Off

Covid-19 and Psoriasis: Is there a link? – Dunya News

Posted: at 1:28 am

Psoriasis flares have long been associated with bacterial and viral infections

ISLAMABAD, (ONLINE) - New research is shedding light on how an infection with Covid-19 may reactivate, or even cause, psoriasis. The skin condition affects about 7.5 million adults in the United States, according to the National Psoriasis Foundation. Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people and it appears Covid may also do so.

Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body, said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvanias Perelman School of Medicine in Philadelphia. Infection with Covid-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin, which is called erythroderma, in many published case reports.

What Makes Your Psoriasis Severe?Your immune system is actually to blame for those itchy, sore patches of skin. Its considered severe when it covers what percentage of your body?

A study from Albany Medical College/Weirton Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for Covid. New psoriasis after a Covid infection was also found. The researchers think this could be because Covid causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think its possible that Covid-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.

Inflammation in the body commonly manifests itself through skin conditions.

The skin is the largest organ in the body, said Robert O. Carpenter, MD, director of wellness at Texas A&M College of Medicine in Bryan, TX. A viral infection like Covid-19 can signal the release of pro-inflammatory factors that can appear as rashes, such as with psoriasis.What are the Symptoms of Covid-Related Psoriasis?

The signs are the same as those of any form of psoriasis. According to the Mayo Clinic, these signs can include:

A patchy, scaly, raised red rash. Psoriasis can also be purple, pink, gray, brown or silver. The rash can appear anywhere on the body. Psoriasis can also look like dandruff.

Dry, cracking skin that sometimes peels

Itching, burning, or painful skin

If I Have Psoriasis, Will COVID Automatically Make It Worse?

Not necessarily.

Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to Covid-19, said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.

As with every aspect of Covid, doctors and scientists are still learning about how serious and widespread a problem psoriasis after Covid-19 may be. We have seen case reports that psoriasis can flare after Covid-19, said Freeman, who is also an associate professor of dermatology at Harvard Medical School. I will say, this has not been a tidal wave more like sporadic cases here and there. So I do not think psoriasis flares are a major post-Covid finding, nor do they necessarily mean you have long Covid. That being said, we know that many different infections can cause psoriasis flares, and so in that respect, it's not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.

Could getting Covid more than once cause psoriasis to flare? Its possible.

Your body can change after having Covid-19, said Carpenter. We dont know the long-term implications, but having Covid-19 repeatedly can increase the risk of long Covid, which can cause many systemic changes in your body."

Another important point: If you take biologics, the immune-modulating therapy to treat psoriasis, getting vaccinated and boosted for Covid is an important step to take to help protect yourself.

Is Psoriasis Itself a Potential Symptom of Covid?

Yes, but we dont know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports, said Gelfand, whos also medical director of the Clinical Studies Unit in the Department of Dermatology at his university. Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly Covid-19 may be appropriate.

If you do have a flare of psoriasis, or get one for the first time after testing positive for Covid, you should also ask your dermatologist about new treatment options.

Original post:
Covid-19 and Psoriasis: Is there a link? - Dunya News

Posted in Psoriasis | Comments Off

Improvement Needed in Study Interventions to Better Skin Self … – AJMC.com Managed Markets Network

Posted: at 1:28 am

A new systematic review has identified common strategies for and gaps in ensuring adherence to self-monitoring for early detection of new or recurrent melanoma, a complex challenge affected by various interacting factors.

The study, using an adaption of the World Health Organization (WHO) framework for adherence, characterized strategies built into the design, conduct, and reporting of melanoma trials, offering insights into potential improvements for these strategies in research. Currently, few high-risk patients routinely perform skin self-examination (SSE) frequently or thoroughly.

There is currently limited practical guidance for the best practices to maximize adherence to SSE in research or practice, wrote the researchers in JAMA Dermatology. Assessment of adherence to an intervention in a trial may provide valuable insights on the ease with which it can be translated into routine clinical practice. Trialists may consider developing a comprehensive adherence plan as part of the study protocol, including strategies for dealing with nonadherence, and may find our adaptation of the WHO adherence framework helpful for this. However, care is needed to ensure strategies are achievable in everyday routine care.

The 18 randomized controlled trials included in the analysis ranged from 40 to over 700 patients. Various approaches to bolster adherence to SSE were leveraged in the trials, including trial design, social support, intervention design, intervention and condition support, and participant support.

Intervention design was used by all trials to increase adherence, 13 of which used theories of health behavior change, 2 of which reported on patient and public involvement in the study design and materials, and 1 of which reported codesign of the intervention with potential recipients.

The most common trial design strategy was eligibility criteria limits, used by 14 of the studies. These criteria typically limited eligibility to patients who spoke English and who were more likely to adhere to self-monitoring practices, assessed with pretests for adherence.

Social support was offered in 5 trials, all of which provided access to health care professionals and services. In some trials, research staff helped with urgent clinical appointments, while in others, information was provided on how to access care and calendar scheduling was enabled for scheduling doctor appointments. Some of these trials offered information on melanoma risk within families through an internet-based education tool.

The researchers noted that no trials used economic support to cover additional costs nor ensured materials were sensitive to health literacy. As a result, they wrote, diversity in the trials may have unintentionally been hindered, leading to underrepresentation of certain groups of patients.

Research is needed to identify adherence interventions that are low cost and can be easily integrated into the workflow of routine clinical practice, including automated digital interventions, explained the researchers. Interventions that require the active participation of health care professionals or large administrative support may be difficult to implement in busy clinical contexts. Evaluation of individual components of a complex intervention may be undertaken using a SWAT [Studies Within A Trial] repository within the host randomized clinical trial: a self-contained study that has been embedded within a host trial with the aim of evaluating or exploring alternative ways of delivering or organizing a particular trial process.

The researchers noted that SWAT may have direct effects on adherence in the host trial while offering generalizable results for other trials and guiding implementation post trial.

Reference

Ackermann D, Bracken K, Janda M, et al. Strategies to improve adherence to skin self-examination and other self-management practices in people at high risk of melanoma: a scoping review of randomized controlled trials. JAMA Dermatol. 2023;159(4):432-440. doi:10.1001/jamadermatol.2022.6478

More:
Improvement Needed in Study Interventions to Better Skin Self ... - AJMC.com Managed Markets Network

Posted in Psoriasis | Comments Off

Reviva Pharmaceuticals Announces Intent to File an IND for Brilaroxazine in Psoriasis After Promising Preclinical Data – Marketscreener.com

Posted: at 1:28 am

Brilaroxazine topical liposomal-gel formulation (brilaroxazine lipogel) demonstrated proof-of-concept efficacy in the imiquimod-induced psoriatic mouse model

IND submission for brilaroxazine lipogel in psoriasis expected in 2024

Reviva has filed composition of matter patent for brilaroxazine-lipogel and a separate patent for use in the treatment of psoriasis

Preclinical efficacy data presented at the ISID 2023 meeting

CUPERTINO, Calif., May 11, 2023 (GLOBE NEWSWIRE) -- Reviva Pharmaceuticals Holdings, Inc. (NASDAQ: RVPH) (Reviva or the Company), a clinical-stage pharmaceutical company developing therapies that seek to address unmet medical needs in the areas of central nervous system (CNS), respiratory and metabolic diseases, has presented promising preclinical data on the potential of novel serotonin-dopamine stabilizer brilaroxazine for the treatment of psoriasis at the First International Societies for Investigative Dermatology (ISID) Meeting in Tokyo, Japan, May 10-13, 2023. The ISID poster is available at revivapharma.com/publications.

The multifaceted activity of brilaroxazine offers the promise to improve the quality of life and provide a novel treatment option for patients with psoriasis, an inflammatory condition stemming from serotonin and dopamine dysfunction, said Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. We were excited to present encouraging preclinical data at ISID 2023 highlighting the therapeutic potential of brilaroxazine lipogel, a novel, proprietary lipogel formulation for the topical treatment of psoriasis. We have filed a composition of matter patent for brilaroxazine-lipogel and a separate patent for its use in psoriasis. Mental illness, including schizophrenia and depression, is a major comorbidity in patients with psoriasis. Brilaroxazine has established a well-tolerated safety profile with robust efficacy in about 300 patients with schizophrenia from Phase 1B and Phase 2 studies. To further explore this therapeutic potential, we intend to submit an investigational new drug application (IND) for brilaroxazine lipogel in psoriasis in 2024.

Psoriasis is a chronic dermal inflammatory disease with a global prevalence of ~125 million. Dopamine (D) and serotonin (5-HT) signaling pathways play an important role in the pathobiology of psoriasis, and lead to increased inflammatory mediators (TNF-, IFN-, IL-1, IL-6, IL-8), keratinocyte activation and deterioration, and worsening symptoms. Current treatments include multiple modalities but are limited by long-term side effects (topicals), toxicities (orals) or risk of immunogenicity, serious infection, and malignancy (biologics). Brilaroxazine (RP5063) is a modulator of D and 5-HT receptors with multifaceted activity that may affect underlying psoriasis pathology. Preclinical studies in the imiquimod-induced psoriatic mouse model (BALB/c) were used to evaluate the potential of topical liposomal-gel formulation of brilaroxazine for the treatment of psoriasis.

Key poster highlights support the therapeutic potential of brilaroxazine lipogel in psoriasis:

2023 GlobeNewswire, Inc., source Press Releases

Posted in Psoriasis | Comments Off

Monthly Archives: May 2023

David Starkey says activists including Black Lives Matter are ‘trying to destroy white culture’ – Daily Mail

I’m a Couples Therapist. Something New Is Happening in … – The New York Times

Countering organized violence in the United States – Brookings Institution

It’s Time for Call of Duty to Return to One Fictional War – GameRant

Are killer robots the future of war? – Al Jazeera English

Tildrakizumab Linked With HRQOL Improvement in Psoriasis in a Real-World Setting – AJMC.com Managed Markets Network

Clinical Utility of Deucravacitinib for the Management of Moderate to … – Dove Medical Press

Covid-19 and Psoriasis: Is there a link? – Dunya News

Improvement Needed in Study Interventions to Better Skin Self … – AJMC.com Managed Markets Network

Reviva Pharmaceuticals Announces Intent to File an IND for Brilaroxazine in Psoriasis After Promising Preclinical Data – Marketscreener.com

The Prometheus League

Breaking News and Updates

Prometheism

Forbidden Fruit

The Evolutionary Perspective

Transtopia Menu

Library Updates

Library Books

Future Euvolution

Lucid Dreams from Childhood

Genetic Revolution

Speciation + Self-Directed Evolution