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.

New treatment enters phase 1 for wide range of inflammatory and autoimmune diseases.

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Inmagene Biopharmaceuticals announces that today the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application for the drug candidate IMG-004, a non-covalent, reversible, third-generation Bruton Tyrosine Kinase (BTK) inhibitor, to proceed to the Phase I clinical trial. Inmagene is developing the drug candidate to potentially treat immunological diseases.

The planned Phase 1 study is a double-blind, randomized, placebo-controlled, single and multiple dose escalation study in healthy subjects. The study aims to explore IMG-004’s safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects.

“This is the third IND clearance Inmagene has obtained since the beginning of 2022,” said Dr. Jonathan Wang, Chairman and CEO of Inmagene. “These achievements have demonstrated Inmagene’s strong innovative capabilities and high efficiency.”

Dr. Jean-Louis Saillot, Inmagene’s Chief Development Officer, said, "BTK inhibition is an attractive target for a variety of inflammatory and autoimmune diseases, based on demonstrated activity or its current evaluation in clinical trials. IMG-004’s improved activity, selectivity, and pharmacokinetic profile in preclinical studies compared to those of other BTK inhibitors point toward a best-in-class potential. We look forward to the initiation of the IMG-004 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with immunological diseases."

About IMG-004

IMG-004 is a non-covalent, reversible small molecule inhibitor targeting Bruton's tyrosine kinase (BTK). Designed specifically for inflammatory and autoimmune diseases that usually require long-term treatment, IMG-004 is potent, highly selective and brain permeable. It was originally discovered by HUTCHMED (China) Limited, with Inmagene assuming development responsibility at the candidate stage.

BTK is a non-receptor intracytoplasmic tyrosine kinase in the Tec family of protein tyrosine kinases. It is involved in innate and adaptive immune responses related to certain immune-mediated diseases.  Given the central role of BTK in immunity pathways, BTK inhibitors may offer a potential therapeutic approach for the treatment of a wide range of inflammatory and autoimmune diseases.

Not sure what this means exactly, I think it's just a formality but worth mentioning.

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UCB announced today that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for bimekizumab for the treatment of adults with moderate to severe plaque psoriasis.

The letter indicates that the FDA cannot approve the application in its current form. The CRL states that certain pre-approval inspection observations must be resolved before approval of the application. We are cooperating with the FDA and are working to address these observations as expeditiously as possible.

UCB is committed to bringing bimekizumab to patients worldwide. In August 2021, bimekizumab received marketing authorization in countries of the European Union (EU)/European Economic Area (EEA) and Great Britain, for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. In January 2022, bimekizumab received marketing authorization in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis and psoriatic erythroderma in patients who are not sufficiently responding to existing treatments. In February and March 2022, bimekizumab received marketing authorization in Canada and Australia, respectively, for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

In context of the CRL, UCB is reviewing its financial guidance for 2022.

Haven’t posted for a looooooooong time!!

I’ve been successfully using adalimumab (humira first then a different brand for the last couple of years) for about 5 years and been pretty much completely clear, however the last couple of months I have started to show a rash all over my chest/shoulders/back.

It’s not the same as the P I had before Humira, it is flat, not itching, no dryness just smooth red blotches of skin. Could this be a different form of P?? Could it be that it’s time to change my treatment??

Feeling a bit apprehensive!!

This study looked at the prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment.

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Introduction
Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders).

Objective
To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment.

Material and methods
Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators.

Results
In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001).

Conclusion
A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

This study tried to understand secretory leukocyte protease inhibitor (SLPI) and psoriasis.

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Background
Secretory leukocyte protease inhibitor (SLPI), a ~12 kDa protein is an important regulator of innate and adaptive immunity and a component of tissue regenerative programs. SLPI expression is markedly elevated in chronically inflamed skin, including that of individuals suffering from psoriasis. However, the role of SLPI in these diseases remains elusive.

Objectives
The poor understanding of the early stages of the development of psoriasis is a major obstacle to successful intervention in the skin pathology. We hypothesized that SLPI and peripheral nerves that might be activated early in the progression of the disease likely form a functional relationship to maintain skin barrier homeostasis and respond to a variety of threats.

Methods
We used skin biopsies of healthy donors and individuals with psoriasis to show expression pattern of SLPI. A role of SLPI in psoriasis was mechanistically assessed using SLPI deficient mice and an imiquimod-induced experimental model of psoriasis.

Results
We show that mice lacking SLPI had exaggerated skin alterations that extended beyond the treatment site in an imiquimod-induced psoriasis. The spatiotemporally distinct skin responses in SLPI deficient mice, compared to their wild-type littermates, resulted from a compromised skin barrier function that manifested itself in heightened transepidermal water loss through the larger skin area surrounding the imiquimod challenged skin. The increased pathogenic skin changes in the absence of SLPI were reversible through pharmacological treatment that blocks a nerve-reflex arc.

Conclusions
Together these data indicate that SLPI plays a protective role in psoriasis through preventing skin dryness, inherent in the pathogenesis of psoriasis, and that this SLPI action depends on neuronal input operating in a reflex manner. These findings reveal a previously unrecognized mechanism that maintains cutaneous homeostasis which involves a crosstalk between the nervous system and a protein anatomically poised to fortify the epidermal permeability barrier.

Just wondering.  This is my hand.  And my fingernail with a little pitting.  

This study looked at the efficacy response rates and safety outcomes through 120 weeks for patients with moderate to severe psoriasis who are treated with Siliq / Kyntheum (brodalumab)

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Background
Brodalumab is a monoclonal antibody that blocks multiple interleukin-17 family cytokines by binding to the shared A subunit of the interleukin-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated.

Objectives
To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab.

Methods
Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI), and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation.

Results
Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120.
Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days, and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles.

Conclusions
Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

I was diagnosed with Ps 2 years ago but I've had PsA for a decade. I have had sporadic issues with depression long before I had this disease so I can't blame everything on Ps! I know what standard depression feels like and this feels different. It hits me like a ton of bricks then it goes away after 10 days or 2 weeks. That isn't, in my experience, how depression works. If I get on antidepressants, by the time they kick in, I feel better. I don't think I have what most shrinks wound consider your run off the mill depression. Has anyone experienced anything like this or is it unique to me? I started a journal to try and pinpoint how and why, but it will likely take a while for me to see a pattern.

I just want some advice from someone who knows what I'm going through. I don't want to divulge much more info on here than I already have so a pm would be better.

Hi - 


Newbie here, hello everyone.



After suffering from psoriasis for >30 years I have yet another consultant appointment this week. I have been using Enstilar effectively over the last year or so which does help but I have so many patches its becoming unmanageable (plus it makes me feel like I could swim the channel I'm so greasy).



I've had light treatment several times which has been effective but the psoriasis returns quite quickly afterwards.



My guess is that I will get offered Methotrexate from the consultant but I really want to avoid having to take it, with all the known side effects and lifestyle modifications. There are some much newer, more effective treatments that I would like to try. I wondered if anyone else has had a similar situation or suggestions on how to drive the discussions. 


Thanks for reading.

I'm new to forum so first of all, hello all! 

I was on Otezla for 2 years and then got on Tremfya 3 months ago. Tremfya was basically as effective as an injection of saline so I'm back on Otezla which does a decent job but not fantastic. Any advice or recommendations?

This months poll above asks: What effect has Exercise had on your psoriasis and/or psoriatic arthritis ?

Voting is open to members and guests and our members can also leave a comment if they wish.

I learned the hard way this week.  No matter that I keep the shower stall clean, using a squeegee on the walls and floors, drying with a cloth after showering.  Each time I shower, the moisturizer creams or the coconut oil makes the shower stall floor slick.

I'd forgotten my razor on the bathroom counter and turned off the shower's flow, quickly stepped out of shower to fetch the razor, quickly hopped back into the shower stall to shave my legs.  A sudden loss of balance and nothing to be done for it.

I fell against the stall's built-in bench, striking my side between my ribs and hip on Tuesday.  I was temporarily immobilized by pain and could only call out in agony.  My partner rushed in, assessed the crisis, covered me with a towel, and sat on the floor nearby until I could move.  

The rest of Tuesday was pained with little mobility.  I slept sitting up.  On Wednesday, a trip to "same day" care for doctor and x-rays took three hours.  But nothing was broken. Kidney is okay.  Heart is okay.  I got prescriptions for Tramadol and Lidocaine Patches.  

I'm resting and hoping to be able to work on Saturday.  

So this is my warning to not try gymnastics in the shower or bath if you are also using moisturizers and/or coconut oil.  (And it's my appeal for sympathy since it still hurts, even though it's 70% better than Tuesday.)

I have to say it’s the best one I’ve seen or been in, it’s easy to navigate and welcoming.
I like the non psoriasis boards a lot too, because although at times psoriasis can be a bit all consuming when you are itchy, sore or whatever, there’s much more to life and it really gives shape to those who take part. If it were just about the P I would probably only pop in occasionally.
I wouldn’t feel comfortable giving the information I give here on other forums but I am very happy with Fred’s approach and I know he and others are keeping watch on it all.

In fact the question is: “Why has Psoriasisclub the nature that we see?”

I think there are a lot of factors that play a role in the nature of Psoriasisclub.
I visit other forums some times, of many kinds and types, e.g. photography, motorcycles, sometimes a technical forum though they are hard to understand, etcetera.
They are mostly helpful also, but have a different atmosphere.

Sometimes I visit facebook psoriasis sites, facebook is kind of a fehtherlight streaming forum with a very low span of attention. And over there I read a lot of nonsense and weird idea on psoriasis. There is a forum of the dutch association, where I sometimes post. They are reasonably good, but there is not so much activity.

So that winds back to partly what Forest said about psoriasisclub concerning adverts and integrity. But there is more to psoriasisclub.
There is knowledge and experience over here. The members together have gathered immense experience, without forcing that experience to others. They tell other members with questions about their personal experiences with medication or show the way to members that do have experience.
It is a factor that is greatly missed by industry.  Yes there is scientific research and statistical proof, but to gain real insight you must dive in to personal experiences.

The strong point is that psoriasisclub has grown into a group of knowledged and friendly friends, spread out over the world, who have never met each other, mostly have never seen each other, but still are friends.

The club has, thanks to Fred, a number of simple rules where above all the rule is to respect each other, and for some reason that really works very well with psoriasisclub.

The club also thanks to Fred, has always the newest news facts about psoriasis and Psoriatic Arthritis. I have never seen that anywhere else. I even know that e.g. in the Netherlands the medical inspections (IGJ) has the weird philosophy that this kind of news should not given to patient as not to give them too much hope. Now that is a weird philosophy. 

The club also has a lot of humour and interesse in each other’s life outside the psoriasis life. Half of what is posted is not about psoriasis but about a lot of other things in life, where we all have our opinions about, sometimes very different and the way that we discuss that has already learnt me lot of things and sometimes changed my view to things that I was sure of.

And last but not least the club has a great Staff…    Kind of weird combination… a cow girl from the States, a fossil seeking gentleman from England, an English speaking hermit living unfindable in the country of France and a Dutch motorcycle girl dancing through life.

But…. It all works.    and I bet this is not all that can be said about psoriasisclub.