This study suggests people with psoriasis could be at higher risk of lung cancer.

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Background:
Although many studies have indicated that Psoriasis (PsO) could contribute to the risk of lung cancer, no study has reported a clear causal association between them. Our aim was to explore the potential causal association between PsO and the lung cancer risk using Mendelian randomization (MR) design.

Methods:
To explore a causal association between the PsO and lung cancer, we used large-scale genetic summary data from genome-wide association study (GWAS), including PsO (n=337159) and lung cancer (n=361586), based on previous observational studies. Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with a complementary with the other two analyses: weighted median method and MR-Egger approach.

Results:
The results of IVW methods demonstrated that genetically predicted PsO was significantly associated with higher odds of lung cancer, with an odds ratio (OR) of 1.06 (95%CI, 1.01-1.12; P=0.02). Weighted median method and MR-Egger regression also demonstrated directionally similar results (All P<0.05). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between PsO and lung cancer.

Conclusions:
Our study provided potential evidence between genetically predicted PsO and lung cancer, which suggested that enhanced screening for lung cancer allows early detection of lung cancer.

This study looked at switches between biologics and how their pattern changed over time with the recent availability of new biologic agents.

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Background:
Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time.

Objectives:
The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents.

Methods:
We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class – i.e. within the same therapeutic class - versus inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression.

Results:
A total of 2,153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared to patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared to patients switching from adalimumab.

Conclusion:
This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

This study suggests artificial intelligence could be better than the PASI score for the assessment of psoriasis severity.

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Background:
PASI score is globally used to assess disease activity of psoriasis. However, it is relatively complicated and time-consuming, and the score will vary due to the inconsistent subjectivity between dermatologists. Therefore, an AI system capable of assessing psoriasis severity will be useful.

Objectives:
To propose a simplified PASI system (Single-Shot PASI) and associated AI models capable of assessing psoriasis severity.

Methods:
Overall, 705 psoriasis images of the trunk's front and back were used in our research. Considering the relatively small number of images, we used data augmentation techniques to expand the data. A psoriasis expert's scores were used as teacher data. Various convolutional neural network models and hyperparameters were adjusted using a fivefold cross-validation. From these adjustments, we discovered that fine-tuning Imagenet2012-pretrained InceptionV3 whose last linear layer was replaced by a two-layer perceptron (30 hidden units and five output units) exhibited the best performance.

Results:
To validate our deep learning system, 10 images were selected as test sets and were excluded from the training sets. The AI assessment of Single-Shot PASI was almost consistent with the clinical severity. We examined whether AI assistance would affect human scoring. In this study, 13 dermatologists and 9 medical students were invited as evaluators. Mean absolute differences from AI scores and standard deviation among evaluators reduced with AI assistance. In addition, the evaluator's scores got close to the teacher's score with AI's assistance.

Conclusions:
We proposed a Single-Shot PASI system and developed an associated AI system capable of assessing psoriasis severity simply by uploading a single clinical image. An easy-to-use scoring system and our freely available AI software would help dermatologists and patients with psoriasis.

Has anyone had psoriasis in their ear canal?  Did you also have an ear infection?  Not the outer ear, but the inside part a Q-Tip might reach?  Would you apply a little steroid ointment, using a Q-Tip?

Following on from this thread Piclidenoson for psoriasis report before phase 3 data release Piclidenoson may soon be available.

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Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, announced today that it is planning to submit its registration plans to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for its lead drug candidate Piclidenoson in the treatment of moderate to severe psoriasis.

Can-Fite recently reported topline results from its Phase III COMFORT™ study which met its primary endpoint with statistically significant improvement over placebo in psoriasis patients and an excellent safety profile for Piclidenoson. Further analysis of the Phase III COMFORT™ data point towards a better safety profile for Piclidenoson as compared to Otezla, which induced gastro-intestinal adverse events in 6% of patients compared with 1% in patients treated with placebo or Piclidenoson. Discontinuation of treatment amongst patients treated with Otezla was significantly higher compared to that of the Piclidenoson treated patients.

A sub-analysis of the efficacy data that divided patients into those who had PASI>25 (more severe psoriasis) and PASI<25 (less severe) at baseline revealed that patients who started with higher PASI values at entry benefitted more from treatment with Piclidenoson as compared to placebo. This result demonstrates the efficacy of Piclidenoson in the treatment of patients with more severe disease.

In its registration plans, Can-Fite will submit the final efficacy and safety results from COMFORT™, a multicenter, randomized, placebo- and active-controlled, double-blind study that assessed the efficacy and safety of Piclidenoson in more than 400 adults with moderate to severe plaque psoriasis together with a request for registration advice to the FDA and EMA. Additionally, current chemistry, manufacturing, and controls (CMC), nonclinical data, and human pharmacokinetic data will be submitted to the agencies along with a pivotal Phase III protocol and other supporting clinical pharmacology plans.

“The additional safety and efficacy data that emerged following our topline Phase III results point to a strong market positioning for Piclidenoson among approved oral psoriasis drugs. Today, a large percentage of people living with psoriasis choose not to be treated with biologics due to reported serious side effects and the need to be treated in a clinic. Similarly, a percentage of patients using Otezla, the leading oral drug for psoriasis, suffer from gastrointestinal issues and discontinue treatment. We believe that if Piclidenoson achieves its primary endpoint once again in an upcoming pivotal Phase III study, Piclidenoson will offer a safe and effective long-term treatment for people living with psoriasis, including those with the most severe cases,” stated Can-Fite Medical Director, Dr. Michael Silverman.

Anyone here heard of or been on bimzelxs for psoriasis? About to start and keen to hear others experiences

The last dose of Methotrexate was on May 5, 2022.  The daily nausea side effect gradually worsened over the five months I tried the medicine.  My skin did mostly clear, though, leaving only very small patches and discoloration where the worst patches were, but it was mostly smooth and free of itch.

Gradually, the skin grew new patches with variable itchiness.  

I increased my dose of Humira (primarily used for Crohn's Disease since 2012) on June 9 to taking it every week rather than every other week.  

First off, I felt better, overall, quickly.  My breathing improved noticeably (I have Crohn's in my lungs as well as gut).  And my energy levels improved.  

My gastroenterologist and I came up with this plan to give weekly Humira a try, just in case it would help the rashes (or make them worse) before switching to something else.  Blood tests had shown the levels of Humira in my sample were barely inside the therapeutic range.  

I'll repeat a spirometry breathing test in August and consult with pulmonologist afterward to see if the breathing  improvement is in my imagination or verifiable.  So many doctor co-pays!  Sigh.

So . . . in the first couple of days after I take the weekly dose of Humira, the rashes look better.  They are mainly where I sweat while skating, lower legs and groin.  But they are nowhere near as wide spread and uncomfortable as they were before using Methotrexate.

I'm using a mild steroidal ointment only between a couple toes on each foot and only rarely.  I've used an over the counter hydrocortisone cream on the spots in my genital area a little more often but not daily.  If I use the steroid ointments later on, I'll be much more cautious because I believe they made the patches worse in the long run as I used them last year under the advice of the first dermatologist I saw (he was an arrogant man who did not give good advice for steroid usage).

My second dermatologist (she's very good!) is on maternity leave but will return soon. I have an appointment with her on August 2.

That's my update for now.  Thanks for reading.

This analysis updates  Ilumya / Ilumetri  (tildrakizumab) efficacy and safety for up to 5 years in patients with and without metabolic syndrome (MetS)

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Background:
Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity.

Objectives:
This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS.

Methods:
This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs).

Results:
reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100-treated patients with MetS, 98 and 167 TIL100-treated patients without MetS, 34 and 30 TIL200-treated patients with MetS, and 111 and 130 TIL200-treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100-treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200-treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS.

Conclusions:
Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.

This study compared the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis.

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Background:
Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice.

Objectives:
To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis.

Methods:
The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) versus all other approved biologics. Secondary outcomes include proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response.

Results:
Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes.

Conclusions:
These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL17A biologics in the real-world setting.

A comprehensive, tri-national, cross-sectional analysis of characteristics and impact of pruritus in psoriasis.

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Background:
Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized.

Objective:
To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis.

Methods:
This cross-sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self-reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps.

Results:
Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (36%) reported overall stronger pruritus. The scalp was the most frequently reported localization of pruritus, even in the absence of skin lesions. Body surface area (BSA) of pruritus was not linked to pruritus intensity, but to BSA of psoriatic lesions (rho = 0.278; P < 0.001). One third of patients (31%) reported impaired sex-life, and 4% had suicidal ideations due to pruritus. In up to one third of patients, psoriasis therapies had little or no effect on pruritus. The only therapeutic option offered to some of these patients were antihistamines, which appeared to be effective in most cases.

Conclusion:
Pruritus is highly prevalent in psoriasis and is linked to a significant burden. Current psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis.

The aim of this study was to assess the impact of covid 19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments.

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Background:
The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments.

Methods:
We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within one month of COVID-19, and had COVID-19 with or without symptoms.

Results:
120 episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20.0%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (p=0.02) and without systemic treatment (p=0.006) when compared with children on biologics. The six children who required hospitalisation were more frequently under non-biologic systemic treatment when compared with the other children (p=0.01), and particularly under methotrexate (p=0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8.0%) developed a psoriasis in the month following COVID-19, mainly a guttate form (p=0.01).

Discussion:
Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Saw my dermatologist couple of weeks ago. He’s suggested going onto Apremilast. Methotrexate helped clear some of my p up but as soon as I went down to 22.5 mg more came back. Blood tests for methotrexate showed my liver (whatever it is they test it for!) was rising. After ultrasound and fibroscan it’s come back not related to methotrexate but NAFLD. Marvellous! Anyway, now waiting to see if they’ll prescribe Apremilast. Fingers crossed!

Cosentyx (secukinumab) demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate to severe plaque psoriasis.

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Background:
Randomised controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease.

Objectives:
To assess the long-term, real-world retention, effectiveness, and safety of secukinumab in routine clinical practice for the treatment of moderate to severe plaque-type psoriasis (PsO).

Methods;
SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries across Europe for an expected duration of up to 5 years in adult patients with moderate to severe PsO, psoriatic arthritis, and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016–October-2018 and were observed for ≥2 years.

Results:
In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Out of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean±SD absolute PASI was 21.0±13.0 at the start of treatment (n=1,564). At Baseline, the mean±SD PASI score reduced to 2.6±4.8 and remained low at Year 1 (2.3±4.3), Year 2 (1.9±3.6) and Year 3 (1.9±3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed.

Conclusions:
Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA.

Line-field confocal optical coherence tomography (LC-OCT) may represent a promising tool in inflammatory skin disorders.

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Background:
Line-field confocal optical coherence tomography (LC-OCT) is a novel, non-invasive technique that provides in-vivo, high-resolution images in both vertical and horizontal sections.

Objectives:
The aim of the study was to evaluate LC-OCT imaging in some inflammatory disorders and to correlate the resulting features with histopathology.

Methods:
The retrospective study included patients with histopathological confirmed diagnosis of plaque psoriasis, atopic eczema and lichen planus, who were imaged with LC-OCT before the biopsy. LC-OCT was performed with the commercially available LC-OCT device.

Results:
A total of 15 adult patients with histopathologically proven plaque psoriasis (N: 5), atopic eczema (N: 5), and lichen planus (N: 5) were included. In all cases, LC-OCT allowed the in-vivo recognition of the main microscopic features of the examined inflammatory skin disease, with a strong correlation with histopathology.

Conclusions:
Although future studies on larger series of patients are necessary, LC-OCT, based on these preliminary findings, may represent a promising tool in inflammatory skin disorders with potential applications including enhanced diagnosis, biopsy guidance, follow-up and treatment monitoring.

Seven differentially expressed and regulated proteins as biomarkers to predict MTX efficacy.

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Background:
Methotrexate (MTX) is the first-line medicine to treat psoriasis. So far, there has been less research on protein biomarkers to predict its efficacy by the proteomic technique.

Objectives:
To evaluate differentially expressed proteins in peripheral mononuclear cells (PBMCs) between good responders (GRs) and non-responders (NRs) after MTX treatment, compared with normal controls (NCs).

Methods:
We quantified protein expression of PBMCs with 4 GRs and 4 NRs to MTX and 4 NCs by isobaric tags for relative and absolute quantification (iTRAQ), analyzing and identifying proteins related to efficacy of MTX in 18 psoriatic patients.

Results:
A total of 3,177 proteins had quantitative information, and 403 differentially expressed proteins (fold change ≥ 1.2, p < .05) were identified. Compared to NCs, upregulated proteins (ANXA6, RPS27A, EZR, XRCC6), participating in the activation of NF-κB, the JAK-STAT pathway, and neutrophil degranulation were detected in GRs. The proteins (GPV, FN1, STOM), involving platelet activation, signaling and aggregation as well as neutrophil degranulation were significantly downregulated in GRs. These proteins returned to normal levels after MTX treatment. Furthermore, Western blotting identified the expression of ANXA6 and STAT1 in PBMCs, which were significantly downregulated in GRs, but not in NRs.

Conclusions:
We identified seven differentially expressed and regulated proteins (ANXA6, GPV, FN1, XRCC6, STOM, RPS27A, and EZR) as biomarkers to predict MTX efficacy in NF-κB signaling, JAK-STAT pathways, neutrophil degranulation, platelet activation, signaling and aggregation.

This is a German multicentre study of patients with psoriasis after 1 year of treatment with Tremfya (guselkumab)

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Background:
PERSIST was a prospective, non-interventional, long-term, German multicentre study of patients with moderate-to-severe psoriasis receiving guselkumab, an approved monoclonal antibody that binds to the p19 subunit of interleukin (IL)-23, in a real-world setting.

Objectives:
Evaluation of the efficacy and safety of guselkumab, and its effect on health-related quality of life (HRQoL), in patients with moderate-to-severe psoriasis who have received 52 weeks of treatment.

Methods:
Patients (≥18 years old) were prescribed guselkumab as per routine clinical practice. End points assessed include Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), target Nail Psoriasis Severity Index (NAPSI), and the Dermatology Life Quality Index (DLQI).

Results:
Overall, 303 patients were enrolled and treated with guselkumab. Mean disease duration was 21.0 years, and 77.2% and 51.2% of patients had received ≥1 prior conventional systemic or ≥1 prior biologic therapy, respectively. Mean PASI score decreased from 16.4 at baseline to 3.0 by Week (W) 28, and further decreased to 2.4 by W52, while the proportion of patients achieving an absolute PASI score of ≤1 increased from 1.3% at baseline, to 50.8% at W28 and to 58.4% by W52. PASI90 and PASI100 responses also showed marked improvements between W28 and W52, regardless of biologic treatment history. Clearance of psoriatic skin was observed in difficult-to-treat areas, with the percentage of patients achieving a PGA score ≤1 increasing between W28 and W52. Guselkumab improved HRQoL; mean DLQI score decreased from 13.7 at baseline to 2.8 by W28, and further decreased to 2.4 by W52. At W52, 64.6% of patients achieved a DLQI score ≤1. The cumulative probability of drug survival was 92.4% at W52.

Conclusions:
Guselkumab is efficacious and well tolerated regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. No new safety signals were observed.

Following on from this thread Tapinarof for psoriasis phase 3 data Tapinarof (VTAMA) is now approved for use on psoriasis by the U.S. Food and Drug Administration (FDA)

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Dermavant Sciences, a biopharmaceutical company dedicated to developing and commercializing innovative therapeutics in immuno-dermatology, today announced that the U.S. Food and Drug Administration (FDA) has approved VTAMA® (tapinarof) cream, 1%, an aryl hydrocarbon receptor agonist, indicated for the topical treatment of plaque psoriasis in adults. This approval makes VTAMA cream the first and only FDA-approved steroid-free topical medication in its class.

“We are delighted with our FDA-approved label for VTAMA cream, which is for adults with psoriasis, regardless of disease severity, and with an unlimited duration of use. In anticipation of today’s approval, we have a fully built commercial infrastructure in place, and I am excited to say we will have product in the channel in the first week of June. As the first and only approved drug in its class in the U.S., the FDA’s approval of VTAMA cream provides an effective new non-steroidal treatment option for millions of adults living with plaque psoriasis and represents a major milestone for Dermavant and its stakeholders,” said Todd Zavodnick, Chief Executive Officer of Dermavant. “At Dermavant, we are committed to advancing novel, patient-focused innovation in immuno-dermatology. As such, we are proud to have developed a topical treatment in VTAMA cream that provides not only efficacy over 52 weeks but can also be used on all body areas, including on sensitive locations, such as face, skin folds, neck, genitalia, anal crux, inflammatory areas, and axillae. In addition, an approximately four month off-treatment remittive effect (median time to first worsening), leads us to believe that VTAMA cream has the potential to become the preferred topical option for this chronically underserved patient population and among the physicians who treat them.”

“Following 20-plus years of minimal innovation in the topical psoriasis treatment space, I believe the approval of VTAMA cream is an important step in establishing a new treatment option for adults with mild, moderate and severe plaque psoriasis ,” said Mark Lebwohl, MD, FAAD, Dean for Clinical Therapeutics and Waldman Professor and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai in New York and lead author of the Phase 3 studies of VTAMA cream published in The New England Journal of Medicine. “As a clinician, I’m excited to finally have a versatile, once-daily, steroid-free topical treatment that is backed by extensive clinical trial data supporting its favorable safety and efficacy profile and a demonstrated remittive effect of approximately four months in patients off therapy.”

Across PSOARING 1 and PSOARING 2, VTAMA cream demonstrated highly statistically significant improvement in Physician Global Assessment (PGA) score of “clear” (PGA=0) or “almost clear” (PGA=1) with a minimum 2-grade improvement compared with vehicle from baseline at week 12. VTAMA cream also demonstrated a highly statistically significant improvement in all secondary endpoints versus vehicle, including ≥75% Improvement in Psoriasis Area and Severity Index (PASI) score (PASI-75) from baseline at week 12. The adverse event (AE) profile of VTAMA cream reported in both PSOARING 1 and PSOARING 2 demonstrated that the majority of AEs were localized to the site of application and were mild to moderate in nature. The most common AEs of subjects treated with VTAMA cream were folliculitis, nasopharyngitis, and contact dermatitis.

This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis.

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Background:
Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives:
To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

Methods:
A systematic search of CENTRAL, Embase, LILACS, and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving the psoriasis population (any age, n ≥50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any pre-specified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multi-stakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.

Results:
Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n=145) or psoriatic arthritis (n=30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors.

Candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, IL23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and Kallikrein 8 (proteomic), tyramine (metabolomic); PsA: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, Integrin b5, MMP-3 and M-CSF(proteomic) and tyramine and mucic acid (metabolomic) and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.

Conclusions:
This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified here to expedite discovery and validation of biomarkers for clinical use.

Bristol Myers Squibb have announced two-year results from the POETYK PSO long-term extension (LTE) trial demonstrating durable efficacy and a consistent safety profile with deucravacitinib treatment in adult patients with moderate to severe plaque psoriasis.

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Clinical efficacy was maintained through up to two years of deucravacitinib treatment, with response rates at Week 60 in the LTE of 77.7% and 58.7% for Psoriasis Area and Severity Index (PASI) 75 and static Physicians Global Assessment (sPGA) 0/1 (clear/almost clear skin), respectively.

“Plaque psoriasis is a chronic, systemic immune-mediated disease associated with multiple serious comorbidities, and there remains a strong unmet need for new treatments, particularly oral medicines, as many patients are undertreated or are dissatisfied with current options,” said Professor Richard B. Warren, Consultant Dermatologist, Salford Royal Hospital, part of Northern Care Alliance NHS Foundation Trust and Professor at The University of Manchester. “Long-term research showing durable efficacy, in addition to a well understood safety profile, is critical for clinicians and patients making treatment decisions, and these new two-year data underscore the potential of deucravacitinib to be an important new oral treatment option for people living with moderate to severe plaque psoriasis who require systemic therapy.”

The overall safety profile of deucravacitinib observed through two years spans 2,482 patient years of treatment and was consistent with that observed in the previously presented pivotal Phase 3 POETYK PSO-1 and POETYK PSO-2 trials. Adverse events (AEs) continued to be predominantly of mild or moderate severity, with the most common AEs continuing to be nasopharyngitis, upper respiratory tract infection and headache. Serious AEs and AEs leading to discontinuation remained low for up to two years, and no emerging safety signals were observed. With additional follow-up in the LTE trial, which coincided with the peak of the COVID-19 pandemic, there was an increased number of reported COVID-19 infections compared to the POETYK PSO-1 and POETYK PSO-2 trials; however, deucravacitinib treatment did not increase the risk or severity of COVID-19 infection. Overall incidence rates of COVID-19 infection and COVID-19-related hospitalization and death in the LTE trial were consistent with background epidemiologic rates. Through two years, no new trends or clinically meaningful changes from baseline in laboratory values, including hematology, chemistry and lipid parameters, were observed.

“At Bristol Myers Squibb, our pioneering research is leading to the potential for novel, well-tolerated treatment options for individuals impacted by serious immune-mediated diseases like psoriasis. These long-term follow up results add to the growing body of evidence for deucravacitinib, a first-in-class, oral, selective allosteric TYK2 inhibitor with a unique mechanism of action, reinforcing its potential to offer patients with moderate to severe plaque psoriasis an oral treatment option that addresses current gaps in care,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb.

Bristol Myers Squibb thanks the patients and investigators involved in the POETYK PSO clinical trial program.

About Deucravacitinib

Deucravacitinib (pronounced doo-krav-a-sih-ti-nib) is an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, representing a new class of small molecules. It is the first and only selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting signaling of interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), key cytokines involved in the pathogenesis of multiple immune-mediated diseases. Deucravacitinib achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Deucravacitinib selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, deucravacitinib does not inhibit JAK1, JAK2 or JAK3.

Deucravacitinib is being evaluated in global clinical trials in multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel diseases. Deucravacitinib is under regulatory review with global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medical Association (EMA) for the treatment of moderate to severe plaque psoriasis and by Japan's Ministry of Health, Labour and Welfare for the treatment of adults with moderate to severe plaque psoriasis, pustular psoriasis and erythrodermic psoriasis.

New data shows Tremfya binds to CD64 positive (CD64+) cells in addition to interleukin (IL)-23 both of which are key components of the immune system.

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Janssen Pharmaceutical announced the first results of the in vitro MODIF-Y studies, supporting a hypothesis that may differentiate the mechanism of first-in-class TREMFYA® (guselkumab) from risankizumab due to the ability of TREMFYA to bind to CD64 positive (CD64+) cells in addition to interleukin (IL)-23 — both of which are key components of the immune system. These findings, which are being presented at the Society for Investigative Dermatology (SID) annual meeting May 18-21, 2022 in Portland, Oregon, demonstrate TREMFYA binds simultaneously to CD64 via its native fragment crystallizable (Fc) region and to IL-23 via its antigen-binding region, suggesting the potential to neutralize IL-23 right at the site where it is secreted.  Further studies will be conducted in vitro and in vivo to generate additional evidence supporting this hypothesis.

IL-23, a cytokine secreted by activated monocyte/macrophage and dendritic cells, is known to be a driver of inflammatory diseases, including plaque psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). CD64 is a receptor that binds the Fc region of immunoglobulin G4 and is highly expressed on the surface of certain immune cells that are major producers of IL-23.

“The initial results of these studies show the potential differentiating mechanism of TREMFYA,” said presenting study author James G. Krueger, M.D., Ph.D., D. Martin Carter Professor in Clinical Investigation and Co-director, Center for Clinical and Translational Science, The Rockefeller University in New York. “Its ability to bind to CD64+ cells may physically place TREMFYA right on the surface of these major IL-23-producing immune cells, which are key drivers of inflammation in diseases such as psoriasis and psoriatic arthritis. This potentially allows TREMFYA to neutralize IL-23 where it is being produced and prevent IL-23 from acting in the local tissue microenvironment.”

The MODIF-Y studies explored mechanisms potentially underpinning therapeutic profile differences between TREMFYA, a fully human monoclonal antibody specific for the p19 subunit of IL-23 with a native Fc region, and risankizumab, a humanized anti-IL-23 monoclonal antibody with a mutated Fc region.

Differentiated, Local Neutralization of IL-23 at its Source

    The results from these studies show that TREMFYA is differentiated from risankizumab by the capacity of TREMFYA to bind via its native Fc region to CD64, which is expressed on IL-23-producing cells.1This raises the possibility that TREMFYA may bind to IL-23 while also being localized to IL-23-producing cells through its binding to CD64, thus neutralizing IL-23 at its cellular source.1Risankizumab shows negligible binding to CD64 due to its mutated Fc region.

    CD64+ mononuclear phagocytes represent the predominant IL-23 source in psoriatic skin and IBD, and increased frequency of CD64+ monocytes correlates with markers of joint disease activity in active PsA.

    These studies also showed that TREMFYA and risankizumab display comparable affinity for binding IL-23 and potency for inhibiting IL-23-mediated signaling.

Potential for Enrichment in Inflamed Tissues

    Binding to CD64 raises the hypothesis that the presence of TREMFYA may be enriched at the intercellular interface between IL-23-producing and -responsive cells within the inflamed tissue. This may in turn enhance the ability of TREMFYA to neutralize IL-23 where it is produced in inflammatory diseases.

The results of these molecular investigations follow previous publications of Phase 3 clinical trials demonstrating the durable, long-term efficacy and safety profile of TREMFYA based on five years of data in plaque PsO and two years of data in PsA.

“This ability of TREMFYA to capture IL-23 right where it is produced, preventing permanent activation of IL-23-responsive cells, may help explain its durable clinical efficacy in psoriatic disease,” said Dan Cua, Ph.D., Vice President, IL-23 Pathway Leader, Janssen Research & Development, LLC. “These molecular studies also inform current and future research that fuel our critical understanding of IL-23 pathway mechanisms, biodistribution patterns, and clinical outcomes, as we seek to provide patients with more efficacious and lasting treatments across a number of inflammatory diseases.”

Further in vivo research is being conducted on the biodistribution of TREMFYA and its correlation to efficacy in the treatment of patients with PsA and IBD, which includes ongoing Phase 3 trials in Crohn’s disease and ulcerative colitis. Janssen is dedicated to continuing to investigate the pathways underlying immune-mediated diseases, focusing on improving the regulation of the immune system to create novel treatments that can effectively address the root cause of disease.