Category Archives: Psoriasis

Guselkumab demonstrates significant improvements in psoriasis symptoms and health-related quality of life (HRQoL), according to week 28 results of the German G-EPOSS study published in the Journal of the European Academy of Dermatology and Venereology. The study also found that guselkumab reduced sexual impairment and perceived stigmatization in participants.1

Researchers Gerdes et al sought to evaluate the efficacy and safety of guselkumab, particularly in the above disease-specific and social domains. It is well-documented that the burden of psoriasis extends beyond physical symptoms, significantly impacting patients' quality of life, leading to psychological distress and social stigma.2

Furthermore, sexual impairment and stigmatization are significant yet often overlooked dimensions of psoriasis-related morbidity. Patients with psoriasis, especially those with genital involvement, are at increased risk of sexual dysfunction and stigmatization.3 In fact, the World Health Organization lists sexual impairment and perceived stigmatization as key components of its comprehensive psoriasis action plan.4

"Stigmatization affects 73%99% of patients with psoriasis and can result in social exclusion, depression, fear of loss of employment and embarrassment, and can impact on relationships/family planning," according to the study's authors.

Researchers conducted the G-EPOSS study, a prospective, non-interventional, multicenter study. Patients with moderate-to-severe plaque psoriasis were enrolled in the study between October 2019 and August 2021 across 44 study sites in Germany.

Participants were required to be 18 years of age and older with a plaque psoriasis diagnosis of moderate-to-severe nature as determined by a baseline Psoriasis Area and Severity Index (PASI) score of greater than 3 and were candidates for systemic therapy. Prospective patients were also required to be candidates for systemic therapy. Apart from biologic therapies, any individuals taking concomitant medications for their psoriasis were permitted to maintain usage of these medications.

All patients received 100 mg of guselkumab at weeks 0, 4, and every 8 weeks afterwards through a total duration of 76 weeks.

In total, 304 patients were part of the safety analysis, having received at least one dose of guselkumab, with 293 included in the evaluable set population. Patients were excluded from the evaluable set population if they lacked post-baseline PASI measurements or deviated significantly from the observational plan. Data was available for different time points: 282 patients at week 12, 252 at week 20, and 265 at week 28. Patient withdrawals before week 28 were minimal, with 6 (2.0%) attributed to adverse events.

Baseline characteristics, such as age, gender distribution, weight, BMI, and disease duration, were recorded. Prior treatment history indicated that a significant proportion of patients had received systemic (58.0%) or biologic (25.9%) therapy before participating in the study.

"Stigmatization affects 73%99% of patients with psoriasis and can result in social exclusion, depression, fear of loss of employment and embarrassment, and can impact on relationships/family planning."

The study demonstrated significant improvements in psoriasis severity and related symptoms with guselkumab treatment. A substantial percentage of patients achieved primary endpoints of PASI3 (83.0%), PASI1 (56.2%), and PASI=0 (35.1%) by week 28. Nail disease and anogenital psoriasis also showed considerable improvements.

Patient-reported outcomes, particularly Dermatology Life Quality Index (DLQI) and Relationship and Sexuality Scale (RSS), indicated enhanced quality of life and sexual satisfaction. DLQI scores improved, with a majority achieving DLQI 01 at W28. RSS responses showed decreased sexual impairment and fear of sexual intercourse, with an increase in satisfaction with sexual frequency.

Perceived stigmatization, as assessed by the Perceived Stigmatization Questionnaire, decreased over time, indicating reduced social discomfort associated with psoriasis.

Safety outcomes showed that adverse events were generally mild, with infections, skin disorders, and musculoskeletal issues being the most common. Drug-related adverse events were infrequent, with no drug-related serious adverse events or withdrawals due to such events.

"The PRO results demonstrate the clinical relevance of Q9 of the commonly used DLQI as a sentinel to trigger further investigations into sexual difficulties or anogenital skin involvement," wrote Gerdes et al. "Such a holistic approach to patient care may not only positively impact the patient's sense of self-esteem but also the patient's overall degree of social engagement and participation. Further results from the final W76 analysis of G-EPOSS will follow and provide further insights."

References

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Guselkumab Demonstrates Significant Improvement in Psoriasis Symptoms and HRQoL, Reduces Sexual Impairment ... - Dermatology Times

Individuals with psoriasis with unexplained arthralgia and non-inflammatory symptoms are at a far greater risk of psoriatic arthritis (PsA) development, according to new findings, providing new information on subclinical PsA.1

These findings resulted from new research conducted due to the lack of real-world data on subclinical PsA, which is described as the existence of arthralgia in psoriasis patients. This was considered invaluable given the noted higher risk of PsA among those with subclinical PsA.

The new analysis was led by Alen Zabotti, from the department of medical and biological sciences at the University Hospital Santa Maria della Misericordia Rheumatology Clinic in Udine, Italy. Zabotti et al. acknowledged that a prior systematic literature review had indicated the lack of data on the transition between psoriasis to PsA.2

These could help to better define outcomes for PsA prevention studies in the context of prevention/interception of PsA and early diagnosis, Zabotti and colleagues wrote. Therefore, this study investigated the subclinical stage of PsA in terms of risk of progression and clinical symptoms, and to describe the clinical features of new-onset PsA in (psoriasis) cases.3

The investigators assessed data drawn from 2 ongoing European prospective cohorts of individuals with psoriasis, looking at both the Italian cohort, RAPSODI (Ultrasonographic Risk Factors to Develop Psoriatic Arthritis in Psoriatic Patients with and Without ClinIcal Arthralgia), and the German PACE cohort (Psoriasis and Psoriatic Arthritis Cohort Erlangen), both of which were longitudinal studies.1

Subjects featured within the 2 cohorts had been given a diangosis with definite psoriasis of the skin or nails by dermatologists. They were also enriched for PsA risk, with many having arthralgia suggesting a potential risk of PsA development.

The investigators looked at study participants that did not have clinical PsA by the time of their entry to the cohort and those with no visible swelling of joints. Subjects with a history of enthesitis, synovitis, dactylitis, or inflammatory back pain were not included in the research, and those who were included were reassessed every half year, being told by the team to report inflammatory symptoms to their designated rheumatologists.

In the period between January 2017 - December 2022, there had been 215 Italian participants enrolled in RAPSODI with psoriasis, of which 66.0% were shown to have baseline arthralgia indicating the presence of subclinical PsA. Within those in the PACE cohort, 169 participants in total between January 2011 - July 2018, all were determined to have subclinical PsA.

The investigators diagnosed new-onset clinical PsA at the time of follow-up through the use of experienced rheumatologists and with CASPAR criteria fulfillment. The team would also characterize the manifestations of subjects new-onset clinical PsA by enthesitis, dactylitis, peripheral arthritis, and axial involvement.

Additionally, the team recorded participants clinical features at the time of PsA diagnosis, some of which included enthesitis index, joint counts, and presence of dactylitis.

There were 384 individuals given a diagnosis of psoriasis who took part in the study, as well as an average follow-up duration of 33.0 months. Additionally, 80.9% of these individuals were shown to have subclinical PsA, indicating there had been an incidence rate of PsA of 7.7 per 100 patient-years.

The investigators reported that their subclinical PsA patients had a significantly higher risk of developing PsA as opposed to subjects that had psoriasis exclusively (HR=11.7, 95% CI 1.57 to 86.7, P = .016). The research team noted that the cumulative incidence function (CIF) estimated the probability of new-onset PsA was about 9.4% (95% CI 4.7% - 10.6%) by the 12-month mark and that it was 22.7% (95% CI 17.2% - 28.6%) by the 36-month mark.

A notable finding was that 58.9% of subjects had been shown to have inflammatory symptoms during the months immediately preceding their diagnosis of PsA, but 83.9% were found to have non-inflammatory symptoms before their PsA diagnosis. Additionally, the most frequent pattern of presentation was shown to be peripheral joint swelling for 82.1% of those with PsA.

We have confirmed that patients with (psoriasis) experiencing unexplained arthralgia, also reporting non-inflammatory symptoms, are at a significantly elevated risk of developing PsA, they wrote. Additionally, peripheral arthritis, mainly oligoarthritis, is the most common PsA presentation in cohorts with PsO enriched for arthralgia.

References

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Psoriasis Patients with Arthralgia At Increased Risk of Psoriatic Arthritis Development - MD Magazine

Alan J. Kivitz, MD

Credit: Altoona Arthritis and Osteoporosis Center

A new study found certain doses of secukinumab had greater odds of alleviating psoriatic arthritis (PsA) symptoms than placebo.1

In general, US patients treated with secukinumab 300 mg and secukinumab 150 mg with loading dose achieved the highest response rates, including ACR50 and ACR70 responses and the proportions of patients showing at least an MCID improvement in the health-related quality-of-life measure HAQ-DI, wrote investigators, led by Alan J. Kivitz, MD, from the Altoona Center for Clinical Research/Altoona Arthritis and Osteoporosis Center.

PsA is linked to reduced quality of life, physical function, and work productivity. Five FUTURE studies have shown secukinumab, a selective inhibitor of interleukin 17A, provides rapid and significant improvement in the symptoms of PsA and has a favorable safety profile.2

Investigators aimed to compare secukinumab and placebo in challenging-to-treat US patients with PsA.1 They pooled data from patients enrolled in phase 3 FUTURE 2 5 studies, excluding FUTURE 1 due to the study including an intravenous loading dose that is not approved by the US Food and Drug Administration (FDA) or the European Commission (EC) for PsA.

The FUTURE 2 5 trials randomized US patients who were in the minority of the total population with a harder-to-treat disease. This means patients may have had a greater body weight, greater tender and swollen joint counts, and a greater likelihood of enthesitis, dactylitis, and prior exposure to tumor necrosis factor inhibitors (TNFi). Patients either received secukinumab 300 or 150 mg with or without a subcutaneous loading dose or placebo.

The team assessed efficacy, health-related quality of life, and safety at week 16. Subgroup analyses examined TNFi status and body mass index (BMI). With logistic regression, they estimated odds ratios for the American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment.

Although 2147 patients were originally randomized, the current pooled analysis only included 279 patients with 55.6% women. Participants had a mean BMI of > 30 kg/m2 and 55.2% had prior TNFi treatment.

Overall, at week 16, patients on secukinumab 300 mg (59.7%; P < .0001) and secukinumab 150 mg with loading dose (43.4%; P < .0001) had significantly greater ACR20 response rates. Patients on secukinumab 150 mg without a loader dose had greater response rates than placebo but was non-significant (32.5%; P = .30).

When evaluating the PASI score at week 16, patients had greater response rates on secukinumab than on placebo, with more improvements on secukinumab 300 mg than secukinumab 150 mg. Compared to placebo (9.1%), more patients on secukinumab had improved nail disease, with mNAPSI75 rates of 36.4, 24.6, and 15% for secukinumab 300, 150, and 150 mg without loading dose, respectively. Patients also had more improvements in health-related quality of life at week 16 when on secukinumab.

Patients responded to secukinumab as early as week 4, and ACR50 and ACR70 responses were greater with any secukinumab dose than placebo. More patients on secukinumab than placebo had a 100% reduction in PsA symptoms.

When evaluating the odds ratio, the findings revealed patients receiving secukinumab 300 mg and 150 mg with loading dose had greater odds of responding to at least 20%, 50%, or 70% of the treatment in tender and swollen joints (ACR 20/50/70) (P < .05) than patients on placebo. This indicates patients on secukinumab 300 mg and 150 mg with loading doses have the greatest clinical response rates. In contrast, Patients on secukinumab 150 mg without loading dose did not have better odds than placebo.

Patients on all doses of secukinumab had greater odds of a 75% greater reduction in PASI scores from baseline (PASI75) compared to placebo (P < .05). As for a 90% of 100% improvement from baseline on the PSAI score (PASI90 and PASI100), only the secukinumab 300 mg group worked significantly better compared to placebo (P < .05).

Secukinumab was also demonstrated to be as safe as placebo, with the frequency of all treatment-emergent adverse events similar for patients receiving secukinumab 300 mg (51.4%), secukinumab 150 mg with loading dose (54.2%), secukinumab 150 mg without loading dose (55.9%), and placebo (64.4%). The most common adverse events were upper respiratory tract infection, nasopharyngitis, nausea, and sinusitis.

Overall, secukinumab brought rapid improvements in disease activity and quality of life. The results suggest secukinumab 300 mg better improves symptoms of PsA and active psoriasis than secukinumab 150 mg.

The team underlined many limitations, including not adjusting for logistic regression analyses, nominal P values were calculated for hypothesis generation, patients were not stratified based on weight or BMI at randomization, radiographic progression data was only available from FUTURE 5, and patients in all groups had variability in vdH-mTSS scores from baseline to week 24.

This analysis also suggests that a loading-dose regimenparticularly for patients receiving secukinumab 150 mgincreases the odds of optimal outcomes in US patients with PsA treated with secukinumab, investigators concluded.

References

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Secukinumab 300 mg May Improve PsA or Active Psoriasis More Than 150 mg - MD Magazine

Laura C. Coates, MBChB, MRCP, PhD

Credit: X (Twitter)

Guselkumab treatment led to early and durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognized areas In biologic-nave psoriatic arthritis (PsA) patients through 2 years, according to new findings.1

These findings represented the conclusion of a new post-hoc analysis of the phase 3, double-blind, randomized, placebo-controlled trial assessing treatment of PsA with guselkumab among adults with active disease. The phase 3 analysis had been carried out in the period between July 2017 - November 2020.

This new post-hoc analysis was led by Laura C. Coates, MBChB, MRCP, PhD, from the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at University of Oxford in the UK. Coates and colleagues noted the 6 GRAPPA disease domains, adding that the GRAPPA guidelines urge achievement of the lowest possible disease activity level across all domains.2

Informed by the GRAPPA treatment goal of achieving the lowest possible level of disease activity in all affected disease domainsthe objective of the present post hoc analysis was to evaluate the long-term (Week 100) effectiveness of guselkumab across GRAPPA-identified PsA domains and related conditions assessed in DISCOVER-2, Coates and colleagues wrote.

As mentioned previously, the research team carried out their post-hoc analyses of the phase 3 data drawn from the DISCOVER-2 study, a trial which had been aimed at subjects who had been biologic or Janus kinase inhibitor-nave and active PsA. Active disease had been defined as maintaining 5 swollen joints minimum as well as 5 tender joints at least and a C-reactive protein level of 0.6 mg/dL or more.

Study subjects were randomized using a 1:1:1 ratio, being treated with either guselkumab every 4 weeks (Q4W) or the same treatment every 8 weeks (Q8W). The alternative was receiving a placebo with crossover to guselkumab in the subsequent period.

The investigators looked at several different domains highlighted by GRAPPA, which included peripheral arthritis, overall disease activity, enthesitis/dactylitis, axial disease, and skin psoriasis. Additionally, the research team assessed PsA-connected issues including uveitis and inflammatory bowel disease (IBD), evaluated through adverse events (AEs) reported up to the 112-week mark.

The team looked at post-baseline changes through the 100-week mark in continuous outcomes, implementing repeated measures mixed-effects models as well as adjusting for patients scores at baseline. Rates of response rates in binary measures were identified by the investigators through the use of non-responder imputation methods.

The research team reported that 90% of the subjects who had been randomized to be treated with guselkumab finished up the process by the 100-week point. Following an initial disease activity decrease with the drug, the team identified sustained signs of success over several of the aforementioned domains of PsA up to Week 100.

The investigators found that the participants rates of reaching their therapeutic targets showed signs of increasing through the 100-week mark with the drug administered to subjects Q4W or every 8 weeks (Q8W). These signs of improvement included low disease activity (LDA) achievement according to the Disease Activity Index for PsA being 62% with Q4W and 59% after Q8W.

The research team also noted enthesitis rates of resolution being 61% and 70% following Q4W and Q8W, respectively, and dactylitis resolution rates being 72% and 83% with Q4W and Q8W, respectively. Furthermore, the team found subjects with 100% improvement in their Psoriasis Area and Severity Index scores (PASI 100) were 59% and 53% with Q4W and Q8W, respectively.

Lastly, those reporting LDA according to the Psoriatic Arthritis Disease Activity Score were 51% and 49% with Q8W and Q4W, respectively, as well as minimal disease activity achievement among 38% and 40% with Q4W with Q8W, respectively.

The investigators found no instances up to the 112-week point of IBD among subjects who had been given guselkumab. Additionally, only a single case of uveitis was observed.

No exacerbations or new onset of IBD were reported, with a single occurrence of uveitis observed through Week 100 in guselkumab-treated patients, aligning with the established safety profile of guselkumab, they wrote.

References

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Guselkumab Led to Improvements Over Several Psoriatic Arthritis Disease Domains - MD Magazine

Etanercept (ETN) treatment continuation in routine clinical practice may lead to benefits for remission and low disease activity among patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis who did not achieve their treatment goals at 12 weeks, according to recent findings.1

These findings resulted from a new study highlighting treatment impacts for those with rheumatic diseases and plaque psoriasis, looking at the period after 12 weeks of treatment with etanercept. This research was led by Eugen Feist from the department of rheumatology, Helios Fachklinik, Sophie-von-Boetticher-Strae 1, 39245, in Vogelsang-Gommern, Germany.

Feist and colleagues noted that prior research on rheumatic disease and psoriasis suggested disease remission rate benefits beyond 12 weeks.2

The primary aim of this prospective, non-interventional study was to evaluate the proportion of patients with rheumatoid arthritis (RA), axSpA, PsA, or PsO who, in routine clinical practice, benefit from the continuation of treatment with etanercept (ETN) beyond 12 weeks, even in cases where the defined treatment goal has not been formally attained by week 12, Feist and colleagues wrote. Patient-reported outcomes were also recorded.

The ADEQUATE, as it was titled, was conducted with a prospective, multicenter, non-interventional design. The investigators carried out the study in Germany, evaluating the effectiveness of etanercept among those diagnosed with rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, or psoriasis.

The research team looked at routine treatment outcomes at the 12, 24, 36, and 52-week marks among the study participants. The treatment administration used by the team abided by the Summary of Product Characteristics (SmPC) guidelines, including warnings, contraindications, precautions, interactions, adverse effects, and dosing guidelines.

Data on study subjects was assessed for up to 52 weeks post-etanercept initiation. Treatment decisions made before enrollment in the study were also evaluated and documented during 5 12-weekly interactions.

As far as primary endpoints, the investigators looked at the proportion of individuals achieving remission and low disease activity by weeks 12 and then 24. They determined their secondary endpoints to be overall adverse event incidence, continuation of treatment despite non-remission at the 12-week mark, and certain patient-reported outcomes.

The research team determined their criteria for inclusion included having a confirmed diagnosis of the 4 aforementioned conditions, adherence to treatment SmPC guidelines, no previous treatment with etanercept (though other biologic treatments were allowed by the tea), and age 18 years. Their criteria for exclusion included contraindications as well as special warnings and precautions from the SmPC.

A total of 254 subjects with psoriatic arthritis, 305 with axial spondyloarthritis, and 70 with psoriasis took part in the study. The investigators found that rates of remission at both week 12 and week 24 were shown to be 19% and 18% for those with axial spondyloarthritis, 38% and 51% for those with psoriatic arthritis, and 7% and 19% for those with psoriasis, respectively.

Similarly, the research team found that rates of low disease activity at the specified points in time were 39% and 45% for axial, 50% and 60% for psoriatic arthritis, and 34% and 51% for psoriasis. An extension of treatment up to 52 weeks led to stable or increased rates of remission and low disease activity.

Furthermore, they found that improvements in fatigue, pain, and depression were noted by the investigators across all of the specified conditions. They did not identify new safety concerns during the course of the study.

This study confirms the effectiveness and safety of ETN in a real-world setting and highlights the potential benefits of continuing treatment with ETN in patients with axSpA and PsA who have not reached their treatment goal after 12 weeks, they wrote. These results mirror those from the same study in patients with RA, demonstrating benefits of extended ETN treatment across a range of rheumatic diseases.

References

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Etanercept Effective for Psoriasis, Rheumatic Disease Among Patients Extending Treatment After 12-Weeks - MD Magazine

A New Hope in the Treatment of Plaque Psoriasis

A recent study published in the New England Journal of Medicine has shed light on a potentially effective treatment for moderate-to-severe plaque psoriasis. The study investigated the efficacy of JNJ-77242113, a novel interleukin-23-receptor antagonist peptide developed by Janssen Research and Development. The results offer promising implications for patients suffering from this chronic skin condition.

The study involved a total of 255 patients with moderate-to-severe plaque psoriasis. These patients were randomly assigned to receive various doses of JNJ-77242113 or a placebo over a course of 16 weeks. The primary endpoint of the study was to observe a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score at week 16. This score is a widely accepted measure for the severity of psoriasis.

The study demonstrated that JNJ-77242113 showed greater efficacy than the placebo, with a significant dose-response relationship observed. This means that as the dosage of JNJ-77242113 increased, the reduction in PASI score also increased significantly. Specifically, in the highest dose group tested of 100 mg twice daily, 79% of patients achieved a PASI 75 response. This is indeed a promising result for a phase 2 trial.

As with any clinical trial, understanding the safety profile and potential adverse events of the tested drug is critical. The most common adverse events reported during this study were COVID-19 and nasopharyngitis, also known as the common cold. However, its important to note that the percentage of patients with at least one adverse event was similar in both the combined JNJ-77242113 dose group and the placebo group, suggesting that the drug may have a comparable safety profile to the placebo.

JNJ-77242113 is an orally administered peptide that selectively blocks interleukin-23 signaling and downstream cytokine production. The role of interleukin-23 in the body is to regulate inflammatory responses and immune system function. By blocking its signaling, JNJ-77242113 can potentially control the overactive immune responses seen in psoriasis, thereby reducing inflammation and the severity of the condition.

Following the positive results from the phase 2 trial, Johnson & Johnson has initiated the pivotal Phase 3 ICONIC clinical development program of JNJ-77242113 in adult and adolescent patients with moderate to severe plaque psoriasis. This next phase will further evaluate the drugs efficacy and safety profile in a larger patient population.

The phase 2 trial results for JNJ-77242113 are indeed encouraging. With its potential efficacy and favorable safety profile, JNJ-77242113 could soon offer a new, effective oral treatment option for patients suffering from moderate-to-severe plaque psoriasis. As we await further results from the Phase 3 trial, the current findings certainly provide a beacon of hope for those affected by this chronic skin condition.

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New Hope in Treatment of Plaque Psoriasis: Study Shows Promising Results - Medriva

There is a high level of similarity in ex-vivo cellular immune responses among moderate-to-severe chronic plaque psoriasis patients, regardless of exclusively receiving reference product adalimumab (Humira) or switching between adalimumab and AVT02, according to new findings.1

These findings represent the conclusion of an analysis of ex vivo exploratory data drawn from a comparative clinical trial. The trial had been conducted to look into the interchangeability between monoclonal antibody AVT02 and the reference product.

This was led by Kathleen Richter, from Alvotech Germany GmbH in Jlich, Germany. Richter and colleagues noted the prior confirmation of AVT02s biosimilarity to adalimumab in a pharmacokinetic study and then in follow-up research confirming safety and efficacy.2,3

The aim was to compare the cell-mediated immunogenicity in participants with moderate-to-severe chronic plaque psoriasis in the AVT02-GL-302 study who received either the RP alone or switched between the RPand AVT02 after ex vivo exposure of isolated PBMCs with the reference product, AVT02, or Keyhole limpet hemocyanin (KLH), using the novel ex vivo comparative immunogenicity assessment (EVCIA), Richter and colleagues wrote.

During the AVT02-GL-302 study, the investigators carried out an ex vivo comparative immunogenicity assessment (EVCIA) to determine cellular immunogenicity among subjects of the study that had chronic cases of psoriasis. The subjects were randomly assigned using a 1:1 ratio by week 12 to be part of the non-switching cohort (given the reference product) or the switching cohort (alternating between adalimumab and AVT02).

The research team gathered peripheral blood mononuclear cells (PBMCs) and they cryopreserved the cells at the week 1 point of baseline, at the week 12 pre-randomization period, and at weeks 16 and 28 among both cohorts. By the time the team began thawing, the cells were re-exposed to several different types of stimuli, some of which included medium alone (negative control), AVT02, reference product, keyhole limpet hemocyanin (KLH) (positive control), RP+KLH, or AVT02+KLH.

The investigators then assessed cytokine release and Th-cell proliferation through the samples collected from 10 subjects per arm. The team thereby ensured a predetermined average cell viability of 75% over all of the different points in time.

The research team found that the cytokine release and Th-cell proliferation continued to be comparable at each of the different points in time between the group that switched and the group that did not switch until the 28-week mark. A notable finding was that in all time points, the overall cellular immune response ended up being heightened post-KLH re-exposure.

This research, which had been derived from the AVT02-GL-302 study, was shown by the team to have reinforced the confirmation of interchangeability seen in the main trial. This may allow for helpful data on the effects of switching treatments on patients cellular immunogenicity.

The innovative EVCIA methodology employed by the investigators in their research here may provide a distinct assessment of both qualitative and quantitative shifts occurring in the cellular immunogenic response caused by switching conditions in vivo.

Initial cellular response could be a valuable additional outcome to predict overall immune response to biologic medicines, currently typically measured by the later development of ADAs and Nabs, they concluded.

The investigators also noted the importance of interpreting the results and considering the research limitations. They noted that the rapid treatment of blood samples was important due to EVCIA sensitivity, adding that delays could impact cell responses and data quality.

In addition, the research team acknowledged that additional confirmation may be needed as the studys small sample sizes and analysis do not have the same needs as larger, prospective, randomized clinical trials.

References

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No Difference in Psoriasis Immune Response Despite Switch Between AVT02, Adalimumab - MD Magazine

Robert Bissonnette, MD

Credit: International Psoriasis Council

Once and twice-daily oral administration of interleukin (IL)-23receptor antagonist peptide JNJ-77242113 met its primary endpoint of achieving a Psoriasis Area and Severity Index (PASI) score reduction of at least 75% or greater among those with moderate-to-severe plaque psoriasis, according to new findings.1

These findings were the results of a study published in The New England Journal of Medicine, conducted with the aim of assessing the performance of JNJ-77242113 as an oral drug. The studys investigators noted the value of effective oral treatment options, as apremilast is known to be only moderately-effective compared to biologics.2

This new research was led by Robert Bissonnette, MD, dermatologist and president of Innovaderm Research Inc. in Montral.

The science behind advanced treatments for immune-mediated inflammatory diseases like PsO has advanced over the last few decades and patients desire treatment options that combine standard of care efficacy, an acceptable safety profile and flexible routes of administration, said Robert Bissonnette, MD, chief executive officer and medical director at Innovaderm Research, Montreal, Canada.3 The Phase 2b FRONTIER 1 data, as reported in NEJM, are very encouraging for the ongoing clinical development program and offer a reason to look forward to the continued research of investigational JNJ-2113 as an oral therapy that may offer an attractive and convenient treatment option for patients.

The study, known as the FRONTIER 1 trial, was led by Janssen Research and Development in collaboration with external medical experts. The research team looked into the efficacy of JNJ-77242113 versus placebo in adult individuals 18 years of age and older that had diagnoses of moderate-to-severe plaque psoriasis.

The trial design, data analysis, treatment administration, and manuscript formation involved the input and participation of the investigators. Individuals deemed to be eligible as subjects met specific criteria, including a diagnosis of psoriasis at minimum a half a year beforehand and suitability for phototherapy or systemic therapy.

Patients were excluded if they had non-plaque or drug-induced psoriasis, or had previously received certain biologic treatments. Enrollment occurred across 60 sites globally, with the trial being a phase 2, double-blind, randomized, placebo-controlled study.

The investigators randomized the participants to distinct doses of JNJ-77242113 or placebo for 16 total weeks, with the groups being given 25 mg once or twice-per-day, 50 mg once-per-day, 100 mg once, or 100 mg twice-per-day.

The research team determined their main endpoint to be a reduction of 75% or more in subjects PASI score from the point of baseline at the 16-week mark. After completion, the participants were given the option to take part in a long-term extension phase known as FRONTIER 2 or to be given their final safety follow-up.

Among their secondary endpoints, the team looked at Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) scores. The investigators also noted that concomitant treatments had been restricted during the trial period.

The research team ended up randomizing a total of 255 subjects, noting that there was a mean PASI score of 19.1 at the point of baseline. The team also found that the participants average duration of their psoriasis was shown to be 18.2 years, adding that 78% of those featured in all trial cohorts had had previous systemic therapy.

PASI 75 response rates at the 16-week mark were shown to be substantially higher in JNJ-77242113-treated groups. They reported rates of 37%, 51%, 58%, 65%, and 79% for 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups versus 9% for placebo, respectively.

These results demonstrated a substantial doseresponse relationship (P<0.001). The investigators did find that adverse events included coronavirus disease 2019 for 12% of those in the placebo group and 11% in each of the JNJ-77242113 groups.

Additionally, the team noted that nasopharyngitis (among 5% and 7%, respectively) was an adverse event reported by subjects. They did add, however, that there was not evidence of a dose-related adverse event increase among those treated with the drug, as incidence of was comparable between each of the JNJ-77242113 dose groups (52%) and the placebo (51%).

In this phase 2 trial, JNJ-77242113showed a doseresponse relationship and greater efficacy than placebo, as measured by the PASI 75 response at week 16, in patients with moderate-to-severe plaque psoriasis, they wrote. Overall, there was no evidence of a relationship between the JNJ-77242113 dose and the incidence of adverse events.

References

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Oral IL-23 Receptor Antagonist Peptide Effective in PASI Reduction for Psoriasis - MD Magazine

A Breakthrough in Psoriasis Treatment

Plaque psoriasis, a chronic skin condition characterized by patches of abnormal skin, often brings about significant discomfort and distress to those affected. The search for an effective treatment has led to a promising discovery: JNJ-77242113, an interleukin-23-receptor antagonist peptide. According to a study published in the New England Journal of Medicine, this innovative oral medication has shown greater efficacy than a placebo in patients suffering from moderate-to-severe plaque psoriasis.

The phase 2 dose-finding trial involved 255 patients and revealed a significant dose-response relationship. This means that higher doses of JNJ-77242113 resulted in a greater therapeutic effect. Remarkably, a higher percentage of patients receiving JNJ-77242113 showed a Psoriasis Area and Severity Index (PASI) 75 response compared to those in the placebo group. PASI 75 response refers to a 75% reduction in the PASI score, a tool used to measure the severity and extent of psoriasis. This achievement serves as the primary endpoint of the trial, marking a significant milestone in psoriasis treatment.

The potency of JNJ-77242113 was clearly demonstrated, with 79 percent of patients in the highest dose group achieving a PASI 75 response at Week 16. This impressive result signals a potential game-changer for those battling moderate to severe plaque psoriasis. Furthermore, the study found no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups, suggesting that even at higher doses, the treatment maintains a favourable safety profile.

The most common adverse events reported during the trial were COVID-19 and nasopharyngitis, a common infection resulting in inflammation of the nasal passages and throat. Its important to note that similar percentages of patients experienced adverse events in both the JNJ-77242113 and placebo groups. The occurrence of these events is not surprising given the ongoing COVID-19 pandemic and the common nature of nasopharyngitis.

The positive results from this phase 2 trial have spurred further research and development. Janssen Research and Development, the company behind JNJ-77242113, has initiated the Phase 3 ICONIC clinical development program. This program, which includes two studies, aims to further assess the efficacy and safety of JNJ-77242113 in adults and adolescents suffering from moderate to severe plaque psoriasis.

Overall, the results of this study are promising. The development and successful trial of JNJ-77242113 mark a significant advancement in the treatment of moderate-to-severe plaque psoriasis. With ongoing research, there is hope that this medication may revolutionize treatment options and bring much-needed relief to those affected by this often debilitating skin condition.

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Breakthrough in Psoriasis Treatment: JNJ-77242113 Shows Promising Results - Medriva

Plaque psoriasis, a chronic autoimmune condition that results in thick, patchy, red skin, affects millions of people worldwide. The search for more effective, targeted treatments is ongoing. Recently, a prospective phase II trial for an oral interleukin (IL)-23 inhibitor, JNJ-77242113, has shown promising results for moderate-to-severe plaque psoriasis patients.

The study revealed response rates as high as 79% at 16 weeks for JNJ-77242113, significantly higher than the placebo response rate of 9%. The drug achieved response rates of 37% to 79% across five dose levels, and there was no evidence of a dose-related increase in adverse events.

Adverse events included COVID-19 and nasopharyngitis, with the most common occurrences being COVID-19, nasopharyngitis, and diarrhea. However, the incidence of serious adverse events across all dose groups was low, at 1%.

The study suggested that the drugs effectiveness could be influenced by body weight and required to be taken on an empty stomach. More extensive trials are needed to confirm these results and determine the optimal dosage for different body weights and health conditions.

The study also indicated a significant increase in Psoriasis Area and Severity Index (PASI) 75 rates across the five doses of JNJ-77242113 versus placebo. Similar response patterns were seen for PASI 90 and PASI 100, which measure the severity of psoriasis symptoms.

Patients on JNJ-77242113 showed improvements in disease-related symptoms and quality of life outcomes. This is particularly important as psoriasis can significantly impact a persons quality of life, causing physical discomfort and emotional distress.

Following the positive results from the Phase 2b trial, Janssen has initiated the pivotal Phase 3 ICONIC clinical development program for JNJ-2113 in adult and adolescent patients. This next phase will provide more extensive data and confirm the safety and efficacy of this promising new treatment.

Compared to injectable biologics, the oral IL-23 inhibitor JNJ-77242113 showed a similar PASI 90 response rate of 60% at 16 weeks. This suggests that oral therapies could provide a viable alternative to injectables, offering greater flexibility and convenience for patients.

The positive results from the Phase II trial of JNJ-77242113 demonstrate significant progress in psoriasis treatment. The development of oral therapies like JNJ-77242113 and deucravacitinib, which has shown effectiveness and safety in real-world clinical practice in Japan, suggest a promising future for psoriasis treatment, marked by greater flexibility, convenience, and effectiveness.

While larger trials are needed to confirm these findings, the current studies provide hope for people living with moderate-to-severe plaque psoriasis, a condition that until now has had limited treatment options.

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Promising Results from Phase II Trial of Oral Interleukin Inhibitor for Psoriasis Treatment - Medriva