Worsening Of Psoriasis Research Articles

Alcohol abuse and discretionary habits in psoriatic patients: impact on IL-17 and IL-23 inhibitor response.

Alcohol abuse is correlated with the onset and worsening of psoriasis, but its effects, as for smoking, on biological therapies are still poorly investigated. This study aimed to determine the prevalence of alcohol abuse and other discretionary habits (such as smoking and sedentary lifestyle) in patients with psoriasis treated with topicals, conventional systemic and biologic therapies. The second objective is to investigate the impact of discretionary habits, focusing on alcohol abuse, on the response to biological therapy. To identify alcohol dependence, the CAGE questionnaire was distributed among patients of our clinic. 305 patients were included with 18% at high risk of alcohol abuse. Clinically, guttate psoriasis and psoriatic arthritis were more common in patients at higher risk of alcohol abuse. Furthermore, patients with an alcohol problem who started biological therapy reported a higher PASI than those who drank less. None of the considered variables seemed to correlate with discontinuation of medication or with lower achievement of the analyzed outcomes (PASI100, PASI90, and PASI≤3). There was a stronger association between alcohol dependence and patients receiving conventional therapy than with patients receiving biologics. The efficacy of biologicals did not seem to be impacted by alcohol consumption, smoking, or sedentary lifestyle.

Risk Factors for Psoriasis Flares: A Narrative Review.

Psoriasis is a chronic inflammatory cutaneous disease with multifactorial pathogenesis involving both genetic and environmental factors as well as the innate and acquired immune response. Several triggering factors may exacerbate or worsen the disease. In this context, we performed a review manuscript with the aim of investigating current literature on psoriasis risk factors, also showing possible mechanisms by which they act on psoriasis. Globally, risk factors can be divided in classic risk factors (eg, mechanical stress, infections and dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations) which have long been known to be responsible for worsening and/or reoccurrence of psoriatic manifestations, and emerging risk factors (eg, biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines) defined as those newly identified risk factors. Accurate patient information and monitoring of risk factors as well as planned follow-ups may help to prevent and treat the worsening of psoriasis and consequently improve the quality of life of psoriatic patients.

Real World Data on Safety and Efficacy of Pegylated Interferon (PEG-IFN) in Patients with Myeloproliferative Neoplasms (MPN)

Introduction: Patients with Myeloproliferative neoplasms (MPN) require cytoreduction to normalise the elevated counts to reduce risk of thrombosis. We present real world data from a single centre in the UK on PEG-IFN in patients with MPN. Methods: Real World prospective data collection of patients who were commenced on PEGIFN between Jan 2014 to July 2022. Patient demographics, indications to treat, dose and response rates at quarterly follow up in year 1 and biannually from year 2 onwards, thrombotic events, transformation, discontinuation rate and adverse events were collected and presented here. Starting dose of PEG IFN was 45 mg/2 weeks; it was increased gradually to a maximum of 180 mg/week. Once complete response (CR) according to ELN criteria was achieved dose was reduced to minimum effective dose. Results: This study accrued 212 patients with MPN who commenced PEGIFN from Jan 2014 to July 2022. Median duration of follow up was 60 m (range 12 - 114 m); 92 males, 120 Females; 93 patients were diagnosed to have Polycythaemia Vera PV), 98 Essential Thrombocythemia (ET) and 21 had Myelofibrosis (MF). 154 patients had mutated JAK2, 41 CAL-R (type 1 in 25 and type 2 in 16), 3 MPL and 13 were negative for any mutations. PEG IFN was chosen as first line treatment in 89 patients and at subsequent line after Hydroxycarbamide (intolerant n=, ineffective n= or contraindicated n= due to ulcers) or phlebotomy in 123 patients. Complete Haematological response according to ELN criteria were achieved and sustained in 141 (66%) at a median of 6 m (range: 3 to 60), Partial response in 52 (24%) and no response in 15 (7%) patients. Molecular response was assessed in JAK2 mutated patients (n=153) and shown in figures 1 and 2 with respect to diagnosis and response rate. Complete molecular response was seen in 4 patients at a median of 58 m. Deeper sustained responses were associated with earlier use of PEG-IFN in the course of disease, younger patients as first line as compared to it being used at second or subsequent line (74% Vs 63%) . PEG IFN was discontinued in 36 patients at 6 to 18 m due to being ineffective in 7, intolerant in 18, unrelated causes in 10 and disease progression/transformation in 3 patients (1 AML 2 MF). Thrombotic events whilst on PEG-IFN were seen in 14 patients (11 arterial and 3 venous) unrelated to control of blood counts, 12 were JAK2+ MPN and 10 patients had PV. Adverse events such as hypothyroidism in 8 (3.7%), grade 1-2 hepatitis in 46 (21.6%), grade 3 hepatitis in 4 (1.8%), alopecia in 2, skin rash in 3, worsening of psoriasis in 2 patients were managed with reduction or temporary suspension of PEG IFN and recommencing at a lower dose and frequency. 29 patients had underlying depression and 22 were stable on anti-depressants, 4 patients came off interferon due to panic attacks. 5 patients developed second primary malignancy on PEG IFN. Conclusion: PEG-IFN is a safe and effective cytoreductive agent in all myeloproliferative neoplasms and is an alternative to Hydroxycarbamide, as a second line option in older patients and a first line option in younger patients. It corrects the elevated counts but also modifies the disease course as evident in JAK2 VAF reduction and sustained haematological responses and reduced risk of thrombosis and transformation. In addition, it is least restrictive in terms of quality of life such as family and holiday planning. Figure 1: Waterfall plot: JAK2 allele burden percentage change on Peg-IFN, each bar represents the % change in allele burden for one patient, and ranked Figure 2: Fall in JAK2 VAF with respect to type of Haematological Response

SAT222 More Than Skin Deep: A Case Of Psoriasis Associated With Hypoparathyroidism

Abstract Disclosure: G. Sheth: None. M. Alsayed: None. Introduction: Primary hypoparathyroidism is commonly encountered post-surgically, however isolated cases are rarely seen without clear risk factors. Severely low calcium levels have been shown to correlate with flare ups and worsening of psoriasis. Treatment of hypocalcemia has been thought to improve and prevent the progression of this skin rash. This case highlights an interesting presentation of psoriasis in which the severity was likely related to hypocalcemia. Clinical Case: 25 y/o F with no prior past medical history presented to the emergency room with diffusely worsening skin rash and fever. She had bilateral erythematous plaques on her anterior legs for a few months that was progressively worsening. A few days prior, she started noticing erythema and scaling on her upper body and back. Her on arrival labs were remarkable for a calcium level of 4.5 mg/dL (8.8-10.4). Patient declined any symptoms at the time but did state she had noticed tingling in her face and hand/foot cramps occurring on and off over the last 6 months. Her EKG was remarkable for a mildly prolonged QT interval. She was treated with IV calcium gluconate 4 grams without improvement in her calcium. She ultimately was placed on a calcium gluconate drip and oral calcium carbonate 2 grams every 2 hours. Meanwhile, her work up revealed a PTH of <6 pg/mL, phosphate of 7 mg/dL, magnesium of 1.7 mg/dL, and vitamin D of 23 ng/mL. To elucidate the cause of her newly diagnosed primary hypoparathyroidism, iron studies were ordered to rule out hemochromatosis and ceruloplasmin to rule out Wilson’s disease, both of which returned negative. She had no history of radiation therapy or prior blood transfusions. She denied any family history of calcium disorders. Therefore, PTH antibody testing was sent to a send out lab and is currently pending. Patient was ultimately weaned off of the calcium drip with low normal calcium values around 7.5-8.5 mg/dL. She was placed on calcium carbonate 2 grams every 6 hours with plans for close outpatient labs and follow up. She was seen by dermatology in the hospital and was diagnosed with erythrodermic psoriasis. She was given an IL-17 inhibitor, Taltz, with significant improvement in her rash over her 2 day hospital stay. Conclusions: This case brings to light the importance of a thorough investigation of primary hypoparathyroidism and to recognize the rare genetic or autoimmune etiology as a possibility. Additionally, this case identifies the association of psoriasis with hypocalcemia. Studies have recognized a correlation of severity of psoriasis in patients with low calcium as was seen in this patient. Moreover, treatment with calcium supplementation may have a role in improving skin manifestations. Presentation: Saturday, June 17, 2023

New Onset and Exacerbation of Psoriasis Following COVID-19 Vaccination: A Review of the Current Knowledge.

COVID-19 vaccination was the main measure to overcome the pandemic. As with other drugs and vaccines, mild to moderate adverse events have been reported following vaccination. In addition, several cutaneous reactions have been described. In particular, there are several reports investigating de novo psoriasis or the exacerbation of psoriasis following COVID-19 vaccination. However, data on the possible pathogenetic mechanisms as well as comprehensive manuscripts on the topic are scant. Thus, the aim of our manuscript was to perform a review of the current literature on post-COVID-19 vaccination exacerbations and new-onset psoriasis in order to offer a wide perspective on this area and to point out possible pathogenetic mechanisms. Research on the current literature was performed following PRISMA guidelines. In total, 49 studies involving 134 patients developing new-onset psoriasis (n = 27, 20.1%) or psoriasis exacerbation (n = 107, 79.9%) were collected. Although cases of de novo psoriasis or a worsening of psoriasis have been reported following vaccination, all of the cases have been successfully treated while overall benefit-risk profile of COVID-19 vaccination does not justify vaccine hesitancy due to the risk of psoriasis being developed or worsening. Certainly, further studies are needed to identify possible pathogenetic mechanisms in order to identify "at-risk" patients. Finally, vaccination should not be discouraged.

Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the phase 3 POETYK PSO program

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the pivotal phase 3 POETYK PSO-1 trial, deucravacitinib was superior to placebo and apremilast using multiple clinical endpoints, including PASI 75 and sPGA score of 0 or 1 (clear/almost clear skin) at Week 16. Clinical efficacy was maintained through Week 52 on continued treatment. We examined long-term clinical efficacy in patients randomized to deucravacitinib on Day 1 in PSO-1 who opted to continue treatment at Week 52 in the long-term extension (LTE) trial.
 Methods: In the 52-week POETYK PSO-1 trial, adult patients were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily; upon trial completion, patients could enter the LTE and receive deucravacitinib. Efficacy endpoints included PASI 75, PASI 90, and sPGA 0/1. Maintenance of response was assessed in Week 16 PASI 75 responders continuing treatment in the LTE. Modified nonresponder imputation (mNRI) was used to impute missing data; patients discontinuing due to psoriasis worsening were imputed as nonresponders. Efficacy results used as-observed data and treatment failure rule imputation.
 Results: Of 332 patients randomized to deucravacitinib in PSO-1, 265 completed the trial and entered the LTE, including 173 Week 16 PASI 75 responders. The mNRI population included 262 deucravacitinib patients entering the LTE, including 171 Week 16 PASI 75 responders; patients failing to reach the Week 112 assessment or discontinuing as of October 1, 2021, were excluded. At Week 112 (LTE Week 60), mNRI response rates among deucravacitinib patients entering the LTE were 82.4% (PASI 75), 55.2% (PASI 90), and 66.5% (sPGA 0/1). Efficacy was maintained up to 112 weeks in Week 16 PASI 75 responders continuing treatment, including PASI 75 response rates at Weeks 16, 52, and 112 (100%, 90.1%, 91.0%, respectively), PASI 90 (62.6%, 64.9%, 63.0%), and sPGA 0/1 (84.2%, 73.7%, 73.5%).
 Conclusion: Clinical efficacy was maintained up to 112 weeks with continuous treatment, further supporting deucravacitinib as an effective treatment for patients with moderate to severe plaque psoriasis.

Placebo Response in Moderate-to-Severe Psoriasis: Prevalence Meta-Analysis of Randomized Controlled Trials

Dear Editor, despite the increase in available treatments and their effectiveness, placebo use has not decreased over time in psoriasis randomised controlled trials (RCTs) (Afach et al. 2021b). Furthermore, more patients in the placebo group experienced a serious adverse event (SAE) due to psoriasis worsening (n=23, 20%) than in the treatment group (n=17, 5%) (Afach et al. 2021a). These results raise the ethical question of using a placebo group in future psoriasis trials. According to European Medicines Agency, variability in placebo response is one reason for using a placebo as a comparator in RCTs evaluating new treatments for plaque psoriasis (CHMP 2004).

The lncRNA PRINS-miRNA-mRNA Axis Gene Expression Profile as a Circulating Biomarker Panel in Psoriasis.

BackgroundThe interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management.MethodsWe investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients’ clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study.ResultsThe lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002).ConclusionsBased on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.

Effect of lockdown due to COVID-19 on health and lifestyle of psoriasis patients: A web-based survey

Background:Chronic skin diseases like psoriasis affect a patient’s physical, psychological, and social functioning as well as well-being, and the lockdown acted as a cofactor in further worsening the quality of life in psoriasis patients.Objective:The objective of the study is to assess the effect of lockdown on the health, lifestyle, and mental well-being of psoriasis patients.Methods:A cross-sectional study was done using an online questionnaire shared through messenger applications to the patients of chronic plaque psoriasis who registered in the psoriasis clinic between August 2020 and December 2020. Data regarding demographics, psoriasis, lifestyle changes, mental status, financial loss, and problems faced during lockdown were collected.Results:Our study included 181 completed questionnaires. The mean age was 37.7 (SD 13.9) years, and 124 (68.5%) were males. Sixty-five (35.9%) patients reported worsening of their psoriasis during the lockdown. Ordinal regression analysis revealed male sex had a higher proportion of worsening of psoriasis (OR 2.56, 95% CI 1.29–5.08, P < 0.007). Duration of illness <6 months (OR 0.14, 95% CI 0.02–0.98, P < 0.04) and feeling relaxed (OR 0.14, 95% CI 0.03–0.56, P < 0.005) were negatively associated with disease worsening.Conclusion:The findings of our study reveal the impact of coronavirus disease 2019 (COVID-19) lockdown on the life of people with psoriasis. A substantial number of patients had a flare of psoriasis during the lockdown. A shorter duration of illness and relaxed mental status was negatively associated with disease worsening. Individuals with financial loss felt anxious or depressed.

27384 Elevated psoriasis severity in obesity is associated with inadequate adiponectin-mediated regulatory T cell response

Obesity, the most common psoriasis comorbidity, is associated with greater psoriasis severity and decreased response to intervention. Disease severity is also increased by diet-induced obesity, in contrast to regular diet (RD) controls in the imiquimod (IMQ)-induced psoriasis-like mouse model. In both humans and mice, obesity is also associated with reduced adiponectin expression. Psoriasis is characterized by an elevated ratio of T helper 17 (TH17) to regulatory T (Treg) cells. However, the role of Treg suppression and adiponectin in obesity-induced worsening of psoriasis is unknown. Immunohistochemical analysis of lesional skin of RD mice treated with IMQ to induce psoriasis revealed increased Tregs (IMQ 116.7 cells/mm2 vs untreated/NT 51.1 cells/mm2, P = .99 vs obese mice without IMQ). Concurrent treatment with intraperitoneal ADP355, an adiponectin mimetic, restored in obese mice the IMQ-induced Treg population (80.15 cells/mm2; P = .67 vs RD mice) and improved psoriasis-like disease (reducing modified Psoriasis Areas and Severity Index/PASI by 40.9%, P < .01; epidermal thickness by 39%, P < .01; and epidermal hyperproliferation by 56%, P < .001). ADP355 also reduced expression of psoriasis-associated inflammatory markers (TNFA by 98%, DEFB4 97%, PI3 89%, IL17A 73%, IL6 57%, and IL22 49%; all P < .001 vs vehicle-injected HFD mice). These data suggest that adiponectin deficiency may increase psoriasis severity with obesity by reducing regional Treg responses. Studies of the ADP355 effect on differentiation, survival, and/or migration of Tregs in healthy and obese individuals are ongoing.

Impact of obesity on skin diseases

Obesity is a chronic disease recognized as a global epidemic; however, the impact of obesity on the skin has received minimal attention. The aim of the study was to evaluate the skin diseases of aggravated by overweight. Material and methods: We conducted a retrospective study of 100 patients admitted in 2019 to the Dermatology Clinic of the Iasi “Sf. Spiridon” County Clinical Emergency Hospital. Of these, 79 adults had BMI above the healthy range. Moreover, the obese patients were divided into 4 BMI classes: overweight (28%), grade 1 obesity (27%), grade 2 obesity (16%) and morbid obesity (8%). Results: All participants underwent dermatological examination for the detection of skin diseases. This article describes the most common skin diseases associated with obesity: skin infections (43%), superinfected skin ulcers (37%), xerosis (23%), plantar hyperkeratosis (10%), worsening of psoriasis (9%), atopic dermatitis (6%), rosacea (4%) and acne (1%). Conclusions: Our study confirm that there is a high prevalence of different skin pathologies in overweight and obese patients.

Дослідження взаємозв'язку циркадного ритму з тяжкістю перебігу псоріазу та ожиріння

The research aim is to identify the correlation between circadian rhythm in terms of changes in the chronotype of human working capacity and severity of psoriasis progression, obesity, and the disease impact on the quality of patients' life. Materials and Methods. The research focuses on the determination of the PASI, BMI, DIAG indexes and a patient's chronotype of working capacity. Results and Discussion. The results of the correlation analysis showed a very high negative correlation between chronotype of patients' working capacity and BMI. They also demonstrated a high negative correlation between PASI and DIAG indicators and chronotype of patients' working capacity. Conclusions. The circadian rhythm changes to the evening chronotype of human working capacity contribute to psoriasis worsening, weight gain, and negative impact of the disease on the quality of patients' life.

AB0532 MAINTENANCE OF RESPONSE THROUGH 5 YEARS OF CONTINUOUS GUSELKUMAB TREATMENT: RESULTS FROM THE PHASE-3 VOYAGE 1 TRIAL

Background:VOYAGE 1, a phase-3, double-blinded, placebo- and active comparator-controlled study evaluated the efficacy and safety of guselkumab (GUS; a fully human anti-interleukin-23 monoclonal antibody) in patients with moderate-to-severe plaque psoriasis.1,2,3Objectives:To assess the efficacy and safety through 5 years of continuous GUS treatment.Methods:In VOYAGE 1, patients were randomized to GUS 100 mg at Weeks 0, 4, 12, then every 8 weeks (q8w); placebo at Weeks 0, 4, 12 followed by GUS 100 mg at Weeks 16, 20 then q8w; or adalimumab 80 mg at Week 0, 40 mg at Week 1, then 40 mg every 2 weeks (q2w) through Week 47. At Week 52, all patients continued open-label GUS through Week 252. Efficacy assessments included proportions of patients achieving ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90, PASI 100), and Investigator’s Global Assessment scores of cleared/minimal or cleared (IGA 0/1, IGA 0). Three statistical methods were used to analyze efficacy: prespecified Treatment Failure Rules (TFR), Nonresponder Imputation (NRI), and As Observed (OBS). For TFR analyses, patients who discontinued study agent due to lack of efficacy, worsening of psoriasis, or use of a protocol-prohibited psoriasis treatment were considered nonresponders. For NRI analyses, patients with missing efficacy data (regardless of the reason) after application of TFR were counted as nonresponders. For OBS analyses, missing data were not imputed. Safety was assessed through Week 264.Results:Among a total of 494 patients randomized to GUS at Week 0 (N=329) and placebo patients who crossed over to GUS at Week 16 (N=165), 76.9% (380/494) continued study agent through Week 252. PASI 90 responses were well-maintained with up to 5 years of continuous GUS use. At Week 52, PASI 90 response rates were 79.7%, 75.5%, and 80.6% based on TFR, NRI, and OBS analyses, respectively; corresponding rates at Week 252 were 84.1%, 66.6%, and 86.6%. Likewise, PASI 100, IGA 0/1, and IGA 0 responses were maintained from Week 52 through Week 252 (Table 1). Efficacy was also maintained through Week 252 in patients randomized to GUS at Week 0 (N=329). Through the end of the study for all patients (GUS group and adalimumab→GUS crossover group; N=774), the proportion of patients reporting at least one adverse event (AE), serious AE, or discontinuation due to AEs were 87.7%, 16.4%, and 6.1%, respectively. Rates of AEs of interest through Week 264 were as follows: serious infections (2.8%), malignancies (nonmelanoma skin cancer [1.7%]; cancer other than nonmelanoma skin cancer [2.3%]), major adverse cardiovascular events (1.0%), and suicidal ideation and behavior (0.6%).Conclusion:High efficacy response rates were maintained (regardless of the method used to analyze data) and no new safety concerns were identified through 5 years of continuous GUS treatment in VOYAGE 1.

The impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biological therapies

Background The beginning of 2020 has been marked by COVID-19 pandemic, with a strong impact on several national health systems worldwide. Objective To describe the impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biologics. Methods A telephone survey was conducted in May 4–10 2020 about the Italian lockdown period (March 9–May 3 2020) in a cohort of psoriatic patients treated with biologics, asking about any exposure to COVID-19, disease status, continuation of therapy, work activity and psychological status through Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS). Results 226 patients were interviewed, with no COVID-19 positive cases. Sixty-three of 226 (27.9%) described worsening of the disease with a correlation to drug withdrawal [43/226 (19%)]. Correlation was also found between the worsening of psoriasis and HADS anxiety, HADS depression, BRS and PSS abnormal scores considered both as categorical and continuous variables. No correlation was found between worsening of psoriasis and work activity. Conclusion Uncertainty about whether biologics could increase the risk of SARS-CoV-2 infection led to drug withdrawal with subsequent worsening of psoriasis. Moreover, psychological status also had a direct influence on the clinical course of the disease.

Meta-analysis results do not reflect the real safety of biologics in psoriasis.

In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. This systematic review and meta-analysis aimed to explore this possibility. Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Continuous treatment with guselkumab maintains clinical responses through 4 years in patients with moderate-to-severe psoriasis: results from VOYAGE 1

Objectives To evaluate the efficacy of guselkumab through four years of continuous treatment for psoriasis. Methods In the phase 3 VOYAGE 1 trial, 837 patients with moderate-to-severe psoriasis were randomized to receive guselkumab 100 mg every-8-weeks, placebo, or adalimumab 40 mg every-2-weeks. Patients in the placebo and adalimumab groups crossed over to receive guselkumab at weeks 16/52, respectively; eligible patients received open-label guselkumab through week 204. Efficacy endpoints (i.e., PASI 75/90/100, IGA 0/1, and IGA 0) were analyzed in the guselkumab group using different methodologies: prespecified treatment failure rules (TFR, patients discontinued due to lack of efficacy, psoriasis worsening, or protocol-prohibited psoriasis treatment considered nonresponders); nonresponder imputation (NRI, patients with missing data counted as nonresponders); and As Observed (OBS, no imputation). Safety was evaluated through week 204. Results At week 204, PASI 90 response rates were 82.2%, 68.4%, and 84.3%, respectively, based on TFR, NRI, and OBS analyses; corresponding proportions at week 52 were 79.7%, 75.5%, and 80.6%. Similarly, PASI 75, PASI 100, IGA 0/1, and IGA 0 responses were maintained from week 52 through week 204. No new safety signals were identified. Conclusions High efficacy response rates were maintained through four years of continuous guselkumab treatment for psoriasis.

AB0759 FOUR-YEAR EFFICACY AND SAFETY OF GUSELKUMAB IN PSORIASIS PATIENTS WITH AND WITHOUT PSORIATIC ARTHRITIS: A POOLED ANALYSIS FROM VOYAGE 1 AND VOYAGE 2

Background:Guselkumab (GUS), a fully human monoclonal antibody, selectively binds and blocks interleukin-23. VOYAGE 1 and VOYAGE 2 are two ongoing Phase 3, randomized, double-blind, placebo (PBO)/active comparator-controlled clinical trials of GUS in patients (pts) with moderate-to-severe psoriasis (PsO).Objectives:This post-hoc analysis reports pooled results through 4 years among a subgroup of moderate-to-severe PsO pts with self-reported psoriatic arthritis (PsA) at baseline.Methods:1829 pts were randomized to GUS 100 mg at Weeks (Wks) 0, 4, and 12, then every 8 wks (q8wk); PBO at Wks 0, 4, and 12, GUS at Wks 16 and 20 then q8wk; or adalimumab (ADA) 80 mg at Wk 0, 40 mg at Wk 1, then 40 mg q2wk until Wk 47 (VOYAGE 1) or Wk 23 (VOYAGE 2). In VOYAGE 1, all pts received open-label GUS 100 mg q8wk during Wks 52-204. VOYAGE 2 incorporated a randomized withdrawal study design, followed by open-label GUS during Wks 76-204. Pooled subgroup analyses using the combined GUS group were conducted based on self-reported PsA status at baseline. Efficacy based on Investigator Global Assessment (IGA) score and Psoriasis Area and Severity Index (PASI) response was assessed using prespecified treatment failure rules (nonresponder status for all time points after discontinuing due to lack of efficacy, worsening of PsO, or use of a prohibited treatment).Results:For pooled VOYAGE 1 and VOYAGE 2 pts (N=1721), combined GUS and ADA to GUS response rates at Wks 100, 156, and 204 were: PASI 90 80.6%, 80.0%, and 80.4%; PASI 100 50.1%, 49.9%, and 52.2%; IGA 0/1 83.6%, 83.3%, and 81.7%; and IGA 0 54.3%, 52.9%, and 53.9, respectively. In the pooled subgroup analysis of pts with and without PsA, response rates were similar across the Wk 100, Wk 156, and Wk 204 evaluations (Table). Rates of adverse events through Wk 204 were comparable for pts with PsA vs those without PsA at baseline.Conclusion:Among GUS-treated pts with moderate-to-severe PsO with and without self-reported PsA at baseline, stable, durable, and high levels of skin responses, as well as comparable safety outcomes, through 4 years were observed.Table.Pooled GUS Response RatesWithout PsA at BaselineWith PsA at BaselineWk 100Wk 156Wk 204Wk 100Wk 156Wk 204N=1301N=1239N=1191N=289N=276N=264PASI 901049(80.6%)1001(80.8%)964(80.9%)233(80.6%)211 (76.4%)206(78.0%)PASI 100648(49.8%)631(50.9%)635(53.3%)149(51.6%)125 (45.3%)125 (47.3%)N=1300N=1235N=1189N=288N=276N=264IGA 0/11086(83.5%)1042(84.4%)979(82.3%)241(83.7%)217 (78.6%)208(78.8%)IGA 0702(54.0%)664(53.8%)649(54.6%)160(55.6%)135 (48.9%)134(50.8%)Acknowledgments:NoneDisclosure of Interests:Kristian Reich Grant/research support from: Janssen Research &amp; Development, LLC, Jan Dutz Grant/research support from: Janssen Research &amp; Development, LLC, Peter Foley Grant/research support from: Janssen Research &amp; Development, LLC, Diamant Thaçi Grant/research support from: Janssen Research &amp; Development, LLC, Ronald Vender Grant/research support from: Janssen Research &amp; Development, LLC, Michael Song Employee of: Janssen Research &amp; Development, LLC, Megan Miller Employee of: Janssen Research &amp; Development, LLC, Yin You Employee of: Janssen Research &amp; Development, LLC, Shu Li Employee of: Janssen Research &amp; Development, LLC, Yaung-Kaung Shen Employee of: Janssen Research &amp; Development, LLC, April Armstrong Grant/research support from: Janssen Research &amp; Development, LLC

Teriflunomide linked with new onset and worsening of psoriasis

Teriflunomide linked with new onset and worsening of psoriasis

Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: A phase 3 extension study in adolescents

Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: A phase 3 extension study in adolescents

Exploring the link between cadmium and psoriasis in a nationally representative sample

Psoriasis, a skin inflammatory disease, originates from dysregulated interactions of the immune system. Cadmium, an environment pollutant, increases the levels of inflammation markers and influences the immune system. To clarify the relationship between cadmium and psoriasis, 5,927 participants, ≥20 years, in the National Health and Nutrition Examination Survey (NHANES) 2003–2006 were studied. Psoriasis severity was assessed using self-reported dermatology questionnaires. Cadmium was measured using blood chemistry. Three adjusted models were applied for the interaction between serum cadmium and severity of psoriasis. Psoriasis patients had significantly higher blood cadmium (0.67 vs. 0.52 μg/L, p = 0.006). There was a strong linear increase in predicted blood cadmium values with an increase in severity of psoriasis (p for trend = 0.002). The β coefficient of the predicted serum cadmium in the “few patches to extensive psoriasis” group was 0.234 (p = 0.002) after adjusting covariates. Participants with severe psoriasis have higher blood cadmium. Environmental exposure to cadmium can predispose to the worsening of psoriasis. Although there are still limitations in this study, such as not included treatment data, these results have substantial public health implications for the general population, as they demonstrate the importance of cadmium exposure prevention, particularly among psoriasis patients.