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Background: As treatment interruptions occur during psoriasis management in clinical practice, it is important to know the duration of clinical response after treatment withdrawal., Objectives: To report time to and predictors of relapse in patients who were tildrakizumab 100 and 200 mg responders (≥75% improvement in Psoriasis Area and Severity Index, PASI 75) at week 28 re-randomized to placebo from reSURFACE 1 trial., Methods: Post hoc analysis of adult patients with moderate-to-severe plaque psoriasis from a 64-week phase 3 trial. Relapse was primarily defined as loss of PASI 75 response. Both relapses defined as loss of PASI 90 and loss of absolute PASI < 2 response were included as sensitivity analyses. PASI 75, PASI 90 and PASI < 2 responders re-randomized to placebo at week 28 and followed up until week 64 were included. The Kaplan-Meier (KM) estimates of the 64-week relapse rate were calculated. The log-rank test to compare KM curves from responders to tildrakizumab 100 and 200 mg was used. Independent predictors of relapse were explored., Results: Median time to loss of PASI 75/PASI 90/PASI < 2 response from week 28 was 142/111/112 days with tildrakizumab 100 mg and 172/140/113 days with tildrakizumab 200 mg, respectively (all not significant). Around 20% of patients did not relapse (either maintained a PASI 75 response or were lost to follow-up) during the 36-week period. Increase in body mass index (BMI) (hazard ratio, HR [95% confidence interval, CI] for loss of PASI 75 response: 1.0345 [1.0112-1.0582]) and increase in disease duration (HR [95% CI]: 1.0151 [1.0028-1.0275] for loss of PASI 75 response) were associated with an increased risk of relapse, regardless of the relapse definition., Conclusions: When treatment is interrupted, tildrakizumab provides durable maintenance of efficacy with a median time to loss of PASI 75 response of 5-6 months, irrespective of the dose. Interventions on modifiable risk factors for relapse, such as BMI, may improve personalized long-term psoriasis management., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: The therapeutic landscape for psoriasis is ever-changing. Risankizumab is the newest approved biologic and one of three currently licensed that targets the p19 subunit of interleukin-23 (IL-23). It is increasingly clear that different biologics vary in their efficacy, effectiveness, and safety profiles, highlighting that there is a need to understand for which patients and in which circumstances to use each drug., Areas Covered: This article summarizes original clinical trial data, and reviews in more detail recent post-marketing studies and meta-analyses that differentiate risankizumab from other biologics. It also briefly explores the evidence for risankizumab in the treatment of other immune-mediated inflammatory diseases., Expert Opinion: Risankizumab is a highly effective biologic for the treatment of moderate-to-severe plaque psoriasis. Recent open-label extension data for risankizumab shows sustained treatment responses to week 136. Indirect comparisons suggest IL-17 inhibitors have a faster onset, though head-to-head comparison with secukinumab shows non-inferiority at week 16 and superiority of risankizumab at week 52. Risankizumab is very well tolerated and data from the IMMhance trial suggests that risankizumab can be used in patients with latent tuberculosis without risk of reactivation.

Background: Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown., Objective: To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK)., Methods: This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss by PASI response level; (iii) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, including FIXTURE., Results: In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI < 50: 22.8%/7.60 h; PASI 50-74: 13.3%/4.45 h; PASI 75-89: 6.4%/2.14 h; PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 vs. ustekinumab and £1061 versus etanercept. Results at 52 weeks were similar., Conclusions: Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom., (© 2018 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Head-to-head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available., Objectives: To assess efficacy and quality of life using matching-adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab., Methods: Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis., Results: In the meta-analysis of studies with active comparators, PASI 90 response rates were 12·7% [95% confidence interval (CI) 5·5-19·8, P = 0·0005], 10·0% (95% CI 2·1-18·0, P = 0·01) and 11·2% (95% CI 3·2-19·1, P = 0·006) higher and PASI 100 response rates were 11·7% (95% CI 5·9-17·5, P < 0·001), 12·7% (95% CI 6·0-19·4, P < 0·001) and 13·1% (95% CI 6·3-19·9, P < 0·001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly., Conclusions: Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: There are limited data on the use of ustekinumab outside of clinical trials., Objectives: To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland., Methods: A retrospective case-note review of 129 patients with psoriasis treated with ustekinumab., Results: Baseline Psoriasis Area and Severity Index (PASI) was 22·9±10·1 (mean±SD). After 16weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n=80/127) of patients, although four patients required concomitant therapy at the 16-week time point. Previous biologic use did show a small, non-significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n=5/17) of individuals weighing 90-100kg and treated with the standard 45mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups <80, 80-90, 100-110 and >110kg, respectively (P=0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n=3/129) of patients., Conclusions: Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short-term therapeutic efficacy with an acceptable short-term safety profile., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: There are few reports of the practical use of adalimumab outside of a clinical trial setting and, to our knowledge, none from the U.K., Objectives: We assessed the efficacy and safety of adalimumab in a cohort of patients with severe psoriasis attending a tertiary dermatology referral centre in the U.K., Methods: A retrospective case-note review was used to identify all patients initiated on adalimumab for psoriasis. RESI;TS: Baseline Psoriasis Area and Severity Index (PASI) was 24+/-11 (range 9-54; n=46). After 4 months' treatment with adalimumab 64% (29/45), of patients had achieved PASI 75 (75% decrease from baseline) whilst 80% (36/45) of patients met NICE criteria for continuation of treatment. Therapy was well-tolerated. Importantly, 68% (21/31) of patients who had previously received another tumour necrosis factor alpha inhibitor met NICE criteria for continuation of treatment at 16 weeks., Conclusions: In a cohort of U.K. patients with severe psoriasis, adalimumab has proved to be a significant addition to the expanding armamentarium of biologics for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs.

Background: Large-scale clinical trials provide clear evidence of the efficacy and short-term toxicity of biologic therapies for psoriasis. However, to date, there are few reports of the practical use of these therapies outside of the trial setting and, to our knowledge, none from a U.K. cohort of patients with psoriasis., Objectives: (i) To assess efficacy and safety of efalizumab, etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21.8 and 21.7, respectively, outside of the clinical trial setting. (ii) To examine our approach to the processes involved in the initiation of biologic therapies in the era of National Institute for Health and Clinical Excellence guidance., Methods: A retrospective case-note review to identify all patients initiated on biologic therapies for psoriasis in a U.K. tertiary referral centre., Results: At 3 months of treatment the efficacy of efalizumab (n = 28), etanercept (n = 70) and infliximab (n = 20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35% and 85%, respectively. All three biologics used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biologic therapy in 30% of cases. Streamlined approaches to screening and funding significantly (P