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Dr. LeonardiThe ongoing rush of safe, highly effective systemic agents for psoriasis has created a new era in which substantial numbers of patients may achieve complete clearance, said an expert at the American Academy of Dermatology 75th Annual Meeting, held here.

In the year 2000, said Craig Leonardi, M.D., two authors called complete skin clearance an unrealistic expectation for patients with psoriasis.1

The fact is that right now, we have many drugs that are so far different from what we used to use even five years ago that complete clearance is a realistic possibility in many of our patients, says Dr. Leonardi. He is adjunct professor of dermatology at St. Louis University and a St. Louis, Missouri-based dermatologist in private practice.

As a reference point, he says, Finally, we have numbers for how methotrexate performs in modern measurement systems. In a well-designed 120-patient trial with modest dose escalation, 41% of patients achieved psoriasis area and severity index (PASI) 75, and 66% achieved PASI 50 at week 16.2 This settles the issue of how well methotrexate indeed performs, Dr. Leonardi says. Although no study patients developed pancytopenia, Its always an issue in the back of my mind. At any one time Ill have hundreds of patients on methotrexate. Based on research in rheumatoid arthritis, he says, risk factors include renal disease, hypoalbuminemia, infection, age and concomitant medication use.

New targets

Since the demise of T-cell inhibitors such as alefacept and efalizumab, Dr. Leonardi says, Weve been concentrating on cytokines and cytokine inhibitors. And its been a very busy time in the pharmaceutical industry and for those of us who do this research.

Among tumor necrosis factor alpha (TNFa) inhibitors that dermatologists may not have heard much about, Certolizumab is one you should definitely remember. It is a pegylated TNF-alpha inhibitor, not a monoclonal antibody. In trials, it is a high-performance skin-clearing drug. In phase 3 testing, 81% and 82% in separate cohorts achieved PASI 75.3 Thats functionally equivalent to infliximab. This is a drug you might be able to reach for. You can prescribe it currently for psoriatic arthritis its approved. And based on phase 3 results in psoriasis, We expect it to sail through the approval process.

Recent approvals in the TNF inhibitor category include biosimilar versions of infliximab, etanercept and adalimumab. And there are others in the pipeline.

New indications for existing drugs include hidradenitis suppurativa and uveitis (adalimumab) and pediatric psoriasis (etanercept). Physicians use golimumab mainly for psoriatic and rheumatoid arthritis, he says. It offers very modest results in psoriasis.

We know that psoriasis is a significant cardiovascular risk factor. Patients with severe psoriasis have a marked increased relative risk of myocardial infarction (MI) compared to mild psoriasis4 and, in another analysis, control subjects.

More recently, research analyzing cardiovascular risk in various treatment groups has shown that TNF inhibitors and methotrexate reduce risk of MI around 50%.5 This is the first time we are seeing evidence that treatments can reduce the risk of myocardial infarction, Dr. Leonardi says.

Additionally, an analysis of cardiovascular risk in patients on TNF inhibitors showed a statistically significant, marked decrease of MI risk, starting at around month 12 and lasting several months thereafter, versus patients on methotrexate.6 Even more amazing, cumulative use of TNF antagonists serially reduced the risk of myocardial infarction. Predicted hazard rate reductions at one, two and three years were 21%, 38% and 51%. And theres probably more to be gained beyond three years. What a wonderful story. Were treating their skin and joints and giving them an increased benefit from a cardiovascular risk perspective, he says.

Among interleukin (IL)-23 inhibitors, he says, a straightforward phase 3 study of tildrakizumab (two doses, versus placebo or etanercept) showed that the higher dose outperforms the lower dose 66% versus 61% in terms of both PASI 75 and physician assessments, without noteworthy safety issues.7 With regard to severe infections, malignancies, major adverse cardiovascular events and drug hypersensitivity reactions, all of these issues are comparable to placebo or to etanercept. This drug appears to be safe and well tolerated.

The phase 3 study of guselkumab did not even consider PASI 75 a primary endpoint, Dr. Leonardi says. Rather, 73% of patients reached PASI 90 at 16 weeks, versus 2.9% of placebo-treated patients.8 This is a significant drug. It distinguishes itself quite clearly from adalimumab in terms of efficacy, with comparable safety findings.

In phase 2 testing, a single dose of risankizumab allowed 87% of patients to reach PASI 75, and 58% to reach PASI 90, at 12 weeks.9 And one-third of these patients remained clear for more than 66 weeks. James Krueger, M.D., Ph.D., has called the drug and immunologic disruptor, says Dr. Leonardi, because its pharmacodynamic effect far exceeds its pharmacokinetic effect. Dr. Krueger is D. Martin Carter Professor in Clinical Investigation at Rockefeller University.

IL-17 inhibitors

In secukinumab four-year data, Efficacy whether its PASI 75 (88.5%), PASI 90 (66.4%) or PASI 100 (43.5%) seems to be maintained.10 The caveat is that this is an as-observed analysis. In other words, the denominator is dropping over time as patients achieving lesser efficacy and tolerability drop out. For most patients, Its not surprising that the efficacy should seem stable over time. It would have been a real problem if we saw efficacy dropping off. Regarding serious adverse events, he adds, There are a lot of zeros in the table, including for Crohns disease. There were two cases of ulcerative colitis. This issue of ulcerative colitis and its association with IL-17 antagonists is ongoing, and were going to have to see how that plays out. Its a rare event less than one in 1000 patients in the secukinumab data.

Unpublished five-year data for ixekizumab, in an analysis which accounted for dropouts over time, shows stable PASI 75, 90 and 100 results (approximately 80%, 70% and 47%, respectively), he says. As for AEs that led to drug discontinuation (13), There were many one-off events that dont seem to have any pattern. All adverse events also appear uncommon and stable over time, he added.

The IL-17 receptor antagonist brodalimumab showed efficacy similar to that of ixekizumab in phase 3 trials (86%/85% PASI75, and 37%/44% PASI 100).11 But early in these trials, he says, concerns for depression, suicidal ideation and behavior appeared. There were six suicides in these trials four in the skin trials and two in psoriatic arthritis trials. The FDA remarked that this was an unprecedented collection of serious issues for any psoriasis trial to date. I would take that to heart.

Amgen abandoned the products development in 2015, and Valeant took it to an FDA hearing in July 2016, at which all 18 FDA reviewers recommended approval although 14 advised implementing a strong risk management program. So this drug has a boxed warning for depression and suicide coming out of the gate, and a risk-management system reminiscent of iPLEDGE, he said.

We must wait and see how our specialty reacts to this, how onerous this will be in our offices and whether or not this drug will gain any traction given that equally efficacious drugs with fewer hassles already exist. Moreover, Dr. Leonardi noted that patients with psoriasis have elevated baseline levels of suicidal ideation and depression versus the general population.12

Development of tofacitinib in dermatology has stopped, said Dr. Leonardi. The FDA has returned the application to Pfizer. The problem with this drug is that patients needed a big dose 15 mg twice a day to have outstanding efficacy. But there was a hard safety signal that occurred much earlier at lower doses. FDA officials noted that in rheumatoid arthritis trials, 14 of the 15 patients who died were on tofacitinib. And there were 34 opportunistic infections, he added, all in tofacitinib-treated patients. In the psoriasis trials, there were more than 1,000 cases of herpes zoster.

However, he said, tofacitinib can be useful off-label for indications including alopecia areata, alopecia-associated nail dystrophy, vitiligo and severe atopic dermatitis. When he prescribed 5 mg of tofacitinib twice-daily for a patient with a 15-year history of alopecia universalis and steroid induced adrenal suppression, One year later, she had more hair than I did.

Disclosures: Dr. Leonardi has been a consultant, researcher and/or speaker for Abbvie, Amgen, Celgene, Coherus, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo, Merck, Merck-Serono, Novartis, Pfizer, Sandoz and Vitae. He also provides phototherapy and has an infusion center.

References

1. Al-Suwaidan SN, Feldman SR. Clearance is not a realistic expectation of psoriasis treatment. J Am Acad Dermatol. 2000;42(5 Pt 1):796-802.

2. Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 389(10068):528-537.

3. http://www.ucb.com/stories-media/press-releases/article/CIMZIA-certolizu... http://www.ucb.com/stories-media/press-releases/article/CIMZIA-certolizu.... Published October 3, 2016. Accessed April 7, 2017.

4. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-41.

5. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-50.

6. Wu JJ, Gurin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor- inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90.

7. Reich K, et al. Tildrakizumab, selective IL-23p19 antibody, in the treatment of chronic plaque psoriasis: results from two randomized, controlled, Phase 3 trials (reSURFACE 1 and reSURFACE 2) [abstract]. Presented as a late breaking abstract at the European Academy of Dermatology and Venereology 2016. October 1, 2016.

8. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405-417.

9. Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebocontrolled trial. J Allergy Clin Immunol. 2015;136(1):116124; e117. 29.

10. Bissonnette R, et al. Secukinumab maintains high levels of efficacy through 4 years of treatments: Results from an extension to a phase 3 study (SCULPTURE). Paper presented at: European Academy of Dermatology and Venereology Annual Meeting.; October 01, 2016; Vienna, Austria.

11. Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373(14):1318-28.

12. Gupta MA, Schork NJ, Gupta AK, Kirkby S, Ellis CN. Suicidal ideation in psoriasis. Int J Dermatol. 1993;32(3):188-90.

Originally posted here:
New systemic psoriasis treatments keep raising bar - ModernMedicine

Psoriasis is a chronic skin disease which results in the person developing red, scaly patches all over their body. Some of the common areas of the body affected the most by the disease are scalp, knees and elbows.

It is a noncontagious disease that has become fairly common among people of all ages and is triggered by inflammatory chemicals produced by white blood cells called lymphocytes, Medicine Netreported.

Although its symptoms may range from small rashes to the entire body covered with thick, red plagues, depending on the level of the disease, it is the incurable nature of the disease that makes it one of the most intimidating skin diseases.

Read: Drug For Psoriasis Shows Results After 4 Weeks: Study

While it cannot be passed from one person to the next via direct contact or transfer of body fluids, it has been known to affect more than one member of the same family, indicating the hereditary nature of the disease, Web MD reported.

Many eminent personalities have previously opened up about suffering from the disease, eroding the social stigma attached to it.

Kim Kardashian

Kim Kardashian West attends the NBCUniversal 2017 Upfront in New York City, May 15, 2017. Photo: Getty Images/Angela Weiss

Reality star and fashionista Kim Kardashian has been perhaps the most vocal when it comes to addressing the struggles of psoriasis. She repeatedly spread awareness regarding the problem on her family reality show, Keeping Up With The Kardashians. However, Kardashian wasnt always as accepting of her chronic skin disease initially, according toHealthline.

She first realized she had psoriasis at the age of 30, incidentally the same age her motherKris Jenner discovered she suffered from the same skin disease. The socialite had almost given up on her career at that point.

Read:Biocon Launches Psoriasis Drug In India; To File IND Application With US FDA This Fiscal

"People don't understand the pressure on me to look perfect," she lamented on the show, Everyday Health reported. "When I gain a pound, it's in the headlines. Imagine what the tabloids would do to me if they saw all these spots?"

But all of that is in the past as the reality star, married to Kanye West, has now embraced her skin abnormality and is even seen advising step-sisterKylie Jenneron how best to tackle the problem as she too has inherited psoriasis.

Kardashian also posts pictures of her skin spots on Twitter.

Art Garfunkel

Grammy Award-winning American singer Art Garfunkel performs on stage at the Bloomfield Stadium in the Israeli city of Tel Aviv, Israel, June 10, 2015. Photo: Getty Images/Gil Cohen Magen

The singer who was one half of Simon & Garfunkel, bringing to the world 60s classics such as "Bridge Over Troubled Water" and "Sound of Silence,"Art Grfunkel also famously suffered from psoriasis and left no stones unturned when it came to treating the same. He had incorrectly learned water from the Dead Sea could help heal the disease. So he decided to try it out, but to no avail.

Ive been told that if you float in the salty, buoyant water, its very good for the skin. Its not so much therapeutic as beautiful, he wrote onhis website.

Britney Spears

Singer Britney Spears performs onstage at the iHeartRadio Music Festival at T-Mobile Arena in Las Vegas, Nevada, Sept. 24, 2016. Photo: Getty Images/Kevin Winter

Although the former teenage popstar secretly suffered from psoriasis for a long time, it was only in 2012 the skin condition of the Toxic singer hit the public eye.

Spears was booked as a judge on X Factor, a job which came with unprecedented stress, causing her skin to breakout in angry red rashes, which were clearly visible when she stepped out on the red carpet at the X Factor premiere party in Los Angeles.

"Britney has had the skin condition for a long time, but it only flares up when she's under extreme pressure, a source told National Enquirer, News reported. Now she can't seem to stop scratching and picking at the sores. She has a psoriasis skin cream, but she says it burns, so she stopped using it."

Dara Torres

Olympian Dara Torres waits for the start of the practice session for the 42nd Toyota Grand Prix of Long Beach Press Day in Long Beach, California, on April 5, 2016. Photo: Getty Images/Frederick M. Brown

Swimmer Dara Torres is one of the very few people who braved the chlorine-filled waters of the swimming pools while most others would remain wary of the same if they were diagnosed with psoriasis. The 12-time Olympic winner instead claimed the water actually soothedthe red spots on her skin, according to Health.

Torres has also been vocal against the stigma attached to the disease, saying athletes who suffer from psoriasis should not be self-conscious of their skin condition, especially when they are out in front of the world, competing to win.

"Psoriasis isn't contagious and it isn't just cosmetic," she says in a public service announcement. "It's a serious disease."

Jon Lovitz

Comedian/actor Jon Lovitz performs during the kickoff of his 20-show residency 'Reunited' with Dana Carvey at The Foundry at SLS Las Vegas in Las Vegas, Nevada, Jan. 6, 2017. Photo: Getty Images/Ethan Miller

Comedian Jon Lovitz is another celebrity who battled psoriasis for years now. The body of the Saturday Night Live and Rat Race star had 75 percentof his body covered in psoriasis spots at one point. However, he refused to give up and worked with a number of dermatologists to find a cure for his condition.

"Don't be embarrassed," he said in an interview with the National Psoriasis Foundation, according to the Health report. "See a dermatologist. A lot of people with psoriasis give up, but don't. Find out what works best for you.

LeAnn Rimes

LeAnn Rimes attends Luli Fama fashion show during Mercedes-Benz Fashion Week Swim 2015 at Cabana Grande at The Raleigh in Miami, Florida, July 20, 2014. Photo: Getty Images/Aaron Davidson

LeAnn Rimes, the country singer, was diagnosed with psoriasis at the age of two, and she proceeded to hide the condition from the world most of her life. At the age of six, 80 percent of her body was covered in red spots, and people around her started referring her as the scaly girl.

She would refrain from wearing short dresses which showed skin on red carpets. However, healthy lifestyle choices and medication prescribed by her dermatologist helped her recover from the problem.

By finally getting control over it instead of it having control over me, I wanted to speak out and let people know that there is hope, Rimes told Shape.

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What Is Psoriasis? Kim Kardashian, Britney Spears And Other Celebrities Suffering From The Skin Disease - International Business Times