Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials. OBJECTIVES: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials. METHODS: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials. RESULTS: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. CONCLUSIONS: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.

Efficacy of secukinumab and adalimumab in patients with psoriatic arthritis and concomitant moderate-to-severe plaque psoriasis: results from EXCEED, a randomized, double-blind head-to-head monotherapy study.

BACKGROUND: Secukinumab [an interleukin (IL)-17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL-12/23 inhibitor) in patients with moderate-to-severe plaque psoriasis. OBJECTIVES: To report 52-week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate-to-severe plaque psoriasis from the head-to-head EXCEED monotherapy study comparing secukinumab with adalimumab. METHODS: Patients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1-4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate-to-severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality-of-life outcomes. Missing data were handled using multiple imputation. RESULTS: Of the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate-to-severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints. CONCLUSIONS: This prespecified analysis in PsA patients with concomitant moderate-to-severe plaque psoriasis in the EXCEED study provides further evidence that IL-17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2).

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report the 3-year efficacy of CZP in plaque psoriasis, pooled from the CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) phase III trials. METHODS: Adults with moderate-to-severe psoriasis for ≥ 6 months were randomized 2 : 2 : 1 to CZP 200 mg, CZP 400 mg or placebo, every 2 weeks (Q2W) for up to 48 weeks. Patients entering the open-label period (weeks 48-144) from double-blinded CZP initially received CZP 200 mg Q2W. Patients not achieving ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 16 entered an open-label CZP 400 mg Q2W escape arm (weeks 16-144). Dose adjustments based on PASI response were permitted during open-label treatment. Outcomes included PASI 75, PASI 90 and Physician's Global Assessment (PGA) 0/1 responder rates, based on a logistic regression model (missing data imputed using Markov Chain Monte Carlo methodology). RESULTS: In total, 186 patients were randomized to CZP 200 mg Q2W and 175 to CZP 400 mg Q2W. At week 48, PASI 75/90 was achieved by 72·7%/51·3% of patients randomized to CZP 200 mg and 84·4%/62·7% randomized to CZP 400 mg. Patients entering the open-label period at week 48, from blinded treatment, received CZP 200 mg Q2W. At week 144, PASI 75/90 was achieved by 70·6%/48·7% patients randomized to CZP 200 mg and 72·9%/42·7% randomized to CZP 400 mg. At week 16, 72 placebo-randomized patients entered the CZP 400 mg Q2W escape arm; 75.7%/58.5% achieved PASI 75/90 at week 144. CONCLUSIONS: Both CZP 200 mg and 400 mg Q2W demonstrated sustained, durable efficacy, with numerically higher responses for some outcomes with 400 mg Q2W.

Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials.

BACKGROUND: Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late-stage development for adult patients with moderate-to-severe AD. OBJECTIVE: To report pooled safety data for baricitinib in patients with moderate-to-severe AD in the clinical development program including long-term extension (LTE) studies. METHODS: This analysis included patient-level safety data from six double-blinded, randomized, placebo-controlled studies (one phase 2 and five phase 3), one double-blinded, randomized, LTE study and one open-label LTE study, reported in three data sets: placebo-controlled, 2-mg - 4-mg extended and All-bari AD. Safety outcomes include treatment-emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. RESULTS: Data were collected for 2531 patients who were given baricitinib for 2247 patient-years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo-controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo-controlled period in baricitinib-treated patients. Frequency of herpes simplex was higher in the 4-mg group (6.1%) vs. the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2-mg IR = 9.6; 4-mg IR = 14.5) were lower vs. the placebo-controlled data set (2-mg IR = 12.4; 4-mg IR = 21.3). In the All-bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2-mg group): two venous thrombosis events (4-mg group) and one death. CONCLUSION: This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.

Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis. METHODS: Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY). RESULTS: Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time. CONCLUSIONS: No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.

A multinational, prospective, observational study to estimate complete skin clearance in patients with moderate-to-severe plaque PSOriasis treated with BIOlogics in a REAL world setting (PSO-BIO-REAL).

BACKGROUND: Anti-tumour necrosis factor (TNF) and anti-interleukin (IL)-12/23 biologics revolutionized plaque psoriasis treatment by enabling ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) in clinical trials. Modern biologics are now reported to achieve PASI 100 (complete skin clearance) in clinical trials. However, real-world evidence of skin clearance rates with biologics is limited. PSO-BIO-REAL was conducted to understand the real-world burden of plaque psoriasis. OBJECTIVE: The primary objective of this observational study was to estimate the proportion of patients who achieved complete skin clearance at 6 months. Secondary objectives included maintenance of response and evaluation of complete skin clearance at 12 months. METHODS: PSO-BIO-REAL was a multinational, prospective, real-world, non-interventional study of skin clearance and patient-reported outcomes (PROs) with biologics. A total of 846 patients from the United States (32%), France (28%), Italy (22%), the United Kingdom (11%) and Germany (8%) were enrolled and followed for one year. Eligible patients were aged ≥18 years with moderate-to-severe plaque psoriasis who had initiated a biologic for plaque psoriasis. Patients could be biologic-naïve or switching biologics (biologic-experienced). Assessments were made at baseline and at months 6 and 12. RESULTS: At 6 and 12 months, 23% and 26% of patients achieved complete skin clearance, respectively. Prior to study entry, 60% were biologic-naïve. The proportion of patients achieving complete skin clearance was lower among biologic-experienced patients (20% at both months 6 and 12) compared with biologic-naïve patients (25% at month 6, 30% at month 12). The rate of complete skin clearance decreased as the number of prior biologics and baseline comorbidities increased. CONCLUSION: Only one in four patients achieved complete skin clearance after 6 months of treatment with biologics. The study indicates there still is an unmet need for more efficacious biologics for patients with psoriasis.

Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks.

BACKGROUND: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. METHODS: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). RESULTS: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low. CONCLUSIONS: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab. What's already known about this topic? Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short-term use in the treatment of patients with moderate-to-severe plaque psoriasis. What does this study add? High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab. There is a favourable long-term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.

Long-term efficacy and safety of secukinumab in the treatment of the multiple manifestations of psoriatic disease.

Psoriatic disease is a multifaceted disorder, which develops in the skin, its appendages and joints. Though characterized by different pathogenic background and clinical manifestations, skin plaque psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are related, sharing key inflammatory mechanisms and hence mode of management. Secukinumab is a fully human monoclonal antibody that selectively binds and neutralizes interleukin-17A. It has been approved for use as a subcutaneous injection for the treatment of moderate-to-severe PsO, PsA and AS. The current review highlights the long-term efficacy and safety profile of secukinumab in the treatment of plaque psoriasis and its multiple manifestations from its phase 3 clinical trial programme. The long-term extension of pivotal trials has shown sustainable efficacy and safety of secukinumab up to 5 years in PsO, PsA and AS and up to 2.5 years in moderate-to-severe nail and palmoplantar PsO through dedicated randomized controlled trials. The effect of secukinumab therapy in all these indications has corresponding effects on improvement in quality-of-life and daily activities. Overall, secukinumab is an effective and safe treatment choice for patients suffering from psoriatic disease in its multiple clinical variants.

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data.

BACKGROUND: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). METHODS: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. RESULTS: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. CONCLUSIONS: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.

Safety of guselkumab in patients with moderate-to-severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies.

BACKGROUND: Long-term evaluation is required to confirm the safety profile of newer biologic agents. OBJECTIVES: To report on pooled safety data from the ongoing VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow-up. METHODS: Patients were randomized to either guselkumab 100 mg at weeks 0 and 4 and every 8 weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every 8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Patients who received adalimumab crossed over to guselkumab at week 52 (VOYAGE 1) and at/after week 28 based on clinical response (VOYAGE 2). Open-label extensions, in which all patients received guselkumab, started at week 52 (VOYAGE 1) and week 76 (VOYAGE 2). Rates of adverse events (AEs) per 100 patient-years (PYs) are presented through 100 weeks of follow-up. RESULTS: Through week 52, observed rates for guselkumab- and adalimumab-treated patients, respectively, were 262·45 per 100 PYs and 328·28 per 100 PYs for AEs, 6·20 per 100 PYs and 7·77 per 100 PYs for serious AEs (SAEs), 1·22 per 100 PYs and 1·79 per 100 PYs for serious infections (SIs), 0·28 per 100 PYs and 0·40 per 100 PYs for malignancies other than nonmelanoma skin cancers (NMSCs), 0·56 per 100 PYs and 0·40 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·40 per 100 PYs for major adverse cardiovascular events (MACEs). Rates among patients treated with guselkumab through week 52 and week 100, respectively, were 262·45 per 100 PYs and 210·41 per 100 PYs for AEs, 6·20 and 6·29 per 100 PYs, for SAEs, 1·22 per 100 PYs and 1·06 per 100 PYs for SIs, 0·28 per 100 PYs and 0·38 per 100 PYs for malignancies, 0·56 per 100 PYs and 0·39 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·38 per 100 PYs for MACEs. Among patients treated with adalimumab, rates of AEs, SAEs, SIs, malignancies, NMSCs, and MACEs showed some variability before and after crossover to guselkumab, although no new safety signals were noted after crossover. CONCLUSIONS: The safety profile for guselkumab remains favourable through 100 weeks of treatment in patients with moderate-to-severe psoriasis.

Certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: pooled analysis of week 16 data from three randomized controlled trials.

BACKGROUND: Certolizumab pegol, an Fc-free, PEGylated, anti-tumour necrosis factor (TNF) biologic, has demonstrated favourable results in three ongoing, phase 3, randomized, double-blinded, placebo-controlled trials in adults with psoriasis. OBJECTIVE: Data were pooled from the ongoing trials to investigate efficacy in selected subgroups and add precision to estimates of treatment effects during the initial 16 weeks of treatment. METHODS: In each trial, patients ≥18 years with moderate-to-severe chronic plaque psoriasis for ≥6 months were randomized to receive certolizumab 400 mg, certolizumab 200 mg or placebo every 2 weeks for 16 weeks. Coprimary endpoints for the pooled analysis were responder rates at Week 16, defined as ≥75% reduction in psoriasis area and severity index (PASI 75) and physician global assessment (PGA) of 0/1 ('clear'/'almost clear' with ≥2-category improvement). Safety was assessed by treatment-emergent adverse events. RESULTS: A total of 850 patients treated with certolizumab 400 mg (N = 342), certolizumab 200 mg (N = 351) or placebo (N = 157) were included in the pooled analysis. At Week 16, PASI 75 and PGA 0/1 responder rates were 80.1% and 63.7% in the certolizumab 400 mg group, 74.5% and 54.6% in the certolizumab 200 mg group, and 7.5% and 2.8% in the placebo group (P < 0.0001 for each dose versus placebo). In patients with and without prior biologic therapy, both doses of certolizumab resulted in substantially higher responder rates versus placebo. The incidence of adverse events was generally similar between the 400 mg and placebo groups, and somewhat lower in the 200 mg group versus placebo. No new safety signals were identified. CONCLUSION: Certolizumab pegol 400 mg or 200 mg every 2 weeks for 16 weeks was associated with statistically significant and clinically meaningful improvements in signs and symptoms of psoriasis in patients with and without prior biologic therapy, and a safety profile consistent with the anti-TNF class in psoriasis.

The German National Program on Psoriasis Health Care 2005-2015: results and experiences.

In 2005, the first national psoriasis survey in Germany revealed large deficits in health care particularly in patients with moderate to severe disease. The consecutive goal was to improve health care for psoriasis countrywide. For this, a large-scale national program was initiated starting with a comprehensive analysis of structures and processes of care for psoriasis. Patient burden, economic impact and barriers to care were systematically analyzed. In order to optimize routine care, a S3 guideline, a set of outcomes measures and treatment goals, were developed. Implementation was enforced by the German Psoriasis Networks (PsoNet) connecting the most dedicated dermatologists. The annual National Conference on Health Care in Psoriasis established in 2009 consented National Health Care Goals in Psoriasis 2010-2015 and defined a set of quality indicators, which are monitored on a regular basis. Currently 28 regional networks including more than 800 dermatologists are active. Between 2005 and 2014 7 out of 8 quality indicators have markedly improved, and regional disparities were resolved. e.g., mean PASI (Psoriasis Area Severity Index) dropped from 11.4 to 8.1 and DLQI (Dermatology Life Quality Index) from 8.6 to 5.9. A decade of experience indicates that a coordinated nationwide psoriasis program based on goal orientation can contribute to better quality of care and optimized outcomes.

Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest.

The German Psoriasis Registry PsoBest was conducted in 2008 in order to investigate the long-term outcomes and safety of systemic treatments for moderate-to-severe psoriasis. Safety analysis of antipsoriatic drugs with special focus on serious adverse events (SAE) for infections, malignancies and major cardiac events (MACE) was done. Nationwide non-interventional patient treatment registry conducted in 251 active dermatology centers. Until June 2012, n = 2444 patients [40 % female; mean age 47.3 (SD 14.1) years; mean duration of disease 18.2 (SD 14.7) years] were recruited, including n = 1791 patients (3842 patient years) with conventional systemic drugs and n = 908 (3442 patient years) with biological drugs. Mean PASI (Psoriasis Area and Severity Index) at inclusion was 14.7, mean DLQI (Dermatology Life Quality Index) 11.1, mean BMI (Body Mass Index) 28.2. The overall rate of SAE per 100 patient years were 1.3 (SD 0.9) per 100 patient years in conventional systemic and 1.5 (SD 1.2) in biologics (p > 0.5, no significant difference). The rates per 100 patient years for single severe adverse events were as follows (systemic/biologics): serious infections, 0.33/0.65 [CI (confidence interval) 0.13-0.54/0.35-0.98]; MACE, 0.56/0.77 (CI 0.29-0.97/0.41-1.31); malignancies (except non-melanoma skin cancer), 0.46/0.49 (CI 0.22-0.84/0.21-0.97). There were no significant differences between single drugs in any of the safety parameters. The conventional systemic and biologic drugs for psoriasis show satisfying safety under routine psoriasis care in Germany with respect to infections, MACE and malignancies.

[Cutaneous granulomatous reactions at botulinum neurotoxin A injection sites: First manifestation of systemic sarcoidosis]. / Granulomatöse Hautveränderungen an Botulinumtoxin-A-Injektionsstellen : Erstmanifestation einer systemischen Sarkoidose.

CASE REPORT: We report a case of granulomatous skin reaction after injection of an unknown botulinum neurotoxin (BoNT) A preparation. Four years after occurrence of skin lesions, systemic sarcoidosis became manifest. CONCLUSION: In addition to injection trauma, the BoNT A preparation may have acted as an immunogenic stimulus leading to cutaneous manifestation of sarcoidosis.

Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial.

BACKGROUND: Tildrakizumab is a high-affinity, humanized, IgG1/κ, anti-interleukin (IL)-23p19 monoclonal antibody that does not bind human IL-12 or p40 is being developed for the treatment of chronic plaque psoriasis. OBJECTIVES: To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: A three-part, randomized, double-blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, 200 mg) or placebo at weeks 0 and 4 (part I) and every 12 weeks thereafter until week 52 (part II). Study drug was discontinued at week 52 and participants were followed through week 72 (part III). Primary efficacy end point was Psoriasis Area and Severity Index (PASI) 75 response at week 16. Adverse events (AEs) and vital signs were monitored throughout the study. RESULTS: At week 16, PASI 75 responses were 33·3% (n = 14), 64·4% (n = 58), 66·3% (n = 59), 74·4% (n = 64) and 4·4% (n = 2) in the 5-, 25-, 100- and 200-mg tildrakizumab and placebo groups, respectively (P ≤ 0·001 for each tildrakizumab dose vs. placebo). PASI 75 response was generally maintained through week 52; only eight of 222 participants who achieved PASI 75 response at week 52 and continued to part III relapsed following discontinuation up to week 72. Possible drug-related serious AEs included bacterial arthritis and lymphoedema (part I), and melanoma, stroke, epiglottitis and knee infection (part II). CONCLUSIONS: Tildrakizumab had treatment effects that were superior to placebo, maintained for 52 weeks of treatment, and persisted for 20 weeks after cessation. Tildrakizumab was generally safe and well tolerated. These results suggest that IL-23p19 is a key target for suppressing psoriasis.

Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey.

BACKGROUND: Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment. OBJECTIVE: To obtain real-world physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies. METHODS: The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom). RESULTS: Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well-being was recognized by 57.2% to 79.3% of physicians. In patients with moderate-to-severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical (≈45%) and biologic (≈30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long-term safety, tolerability, efficacy and costs (biologics). CONCLUSION: Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long-term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.

The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study.

BACKGROUND: Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti-TNF therapy in 2005 have extended medical management options. AIM: To determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti-TNF therapy. METHODS: Adult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log-linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described. RESULTS: During 1998-2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): -1.12% to 10.16%). From 2005-2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: -21.32% to -10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011. CONCLUSION: The total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti-TNF therapy in this patient population.