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Background: Secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate‐to‐severe psoriasis. Trial protocols specify transition periods and prohibit concomitant psoriasis medication. Data are therefore needed on secukinumab effectiveness and safety in routine clinical practice. Objectives: The PROSPECT study assesses prior and concomitant psoriasis treatments and transition periods in subjects receiving secukinumab. Here, we report interim effectiveness and safety data for secukinumab in the context of prior and concomitant treatments. Methods: PROSPECT is an ongoing 24‐week, single‐cohort, non‐interventional study. Subjects with moderate‐to‐severe psoriasis with a decision to receive secukinumab 300 mg were included. Results: Of 1988 subjects, 1238/1988 (62.4%) were male, and mean age was 48.1 ± 13.7 years. Mean baseline Psoriasis Area and Severity Index (PASI) score was 17.7 ± 12.5. 90.9% of subjects had prior systemic treatment. Concomitant treatment was recorded in 44.3% of subjects. Median duration of transition period was 14.0, 30.0 and 44.5 days from prior topical, conventional systemic and biologic treatments. At Week 24, PASI75/90/100 was reached by 86.1%, 68.5% and 39.7% of subjects who started secukinumab treatment at baseline. No unexpected safety signals were observed. Conclusion: PROSPECT provides a large prospective real‐world analysis of secukinumab treatment and includes prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real‐world setting. Secukinumab effectiveness and safety were comparable to that seen in the phase 2/3 secukinumab clinical trial programme. [ABSTRACT FROM AUTHOR]

Dear Editor, Psoriasis is a chronic inflammatory skin disorder, which, in cases of moderate-to-severe disease, requires long-term systemic therapy.1 For patients with an inadequate response or intolerance to a specific systemic therapy, switching psoriasis treatments is a common practice that may improve outcomes. At week 24, 19 (83%) patients receiving FAE and 31 (63%) patients receiving MTX switched to ixekizumab, while 48 (98%) patients receiving ixekizumab continued treatment. Efficacy and safety of ixekizumab after switching from fumaric acid esters or methotrexate in patients with moderate-to-severe plaque psoriasis naïve to systemic treatment. [Extracted from the article]

Summary: Background: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate‐to‐severe chronic plaque psoriasis. Objectives: To consider the benefits and risks of tofacitinib in patients with moderate‐to‐severe psoriasis. Methods: Data were pooled from one phase II, four phase III and one long‐term extension study comprising 5204 patient‐years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. Results: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. Conclusions: Tofacitinib has a benefit–risk profile in moderate‐to‐severe psoriasis consistent with that of other systemic treatments. What's already known about this topic? Psoriasis is a chronic, systemic inflammatory disease, which has a significant impact on patients' health‐related quality of life.Although several existing psoriasis treatments are efficacious and well tolerated in many patients, some patients require treatment switching, and a proportion of patients remain untreated or undertreated.Potential challenges to the use of existing therapies include safety issues and limited efficacy in some patients with conventional oral psoriasis treatments, inconvenience of topical treatments and the requirement for parenteral administration of biologics. What does this study add? Consistent efficacy and a safety profile consistent with that seen in rheumatoid arthritis, psoriatic arthritis and ulcerative colitis were demonstrated for oral tofacitinib in patients with moderate‐to‐severe psoriasis.Tofacitinib has a benefit–risk profile in patients with moderate‐to‐severe psoriasis that is consistent with that of other systemic psoriasis treatments. Linked Comment: Fleming. Br J Dermatol 2019; 180:13–14. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Adalimumab (Humira®, AbbVie Inc., North Chicago, IL, U.S.A.) is a fully human monoclonal antibody specific for tumour necrosis factor‐α that is approved to treat adults with moderate‐to‐severe chronic plaque psoriasis. Objectives: To assess long‐term safety for patients with psoriasis receiving adalimumab in clinical studies. Methods: Adalimumab safety data from adults with psoriasis who received at least one adalimumab dose in 18 clinical trials were evaluated. Adalimumab was delivered subcutaneously in all treatment regimens. Treatment‐emergent adverse events (AEs) were collected from the first dose to 70 days after the last dose or cut‐off date (31 December 2015). AE incidence rates were expressed as events per 100 patient‐years (E/100 PYs) of adalimumab exposure. Standardized incidence ratios (SIRs) for malignancies and standardized mortality ratios (SMRs) were calculated. Results: Cumulative exposure was 5429·7 PYs in 3727 patients. Overall, there were 16 536 AEs (304·6 E/100 PYs). The most common AEs were nasopharyngitis, upper respiratory infection and headache (23·7, 12·9 and 7·9 E/100 PYs, respectively). Incidence rates for serious infections, tuberculosis and opportunistic infections were 1·8, 0·3 and 0·02 E/100 PYs, respectively. Incidence of malignancy excluding nonmelanoma skin cancer (NMSC) was 0·8 E/100 PYs [SIR 0·86, 95% confidence interval (CI) 0·58–1·23]. Incidences of NMSC and melanoma were 0·6 and 0·2 E/100 PYs, respectively. The SIR was 1·55 (95% CI 1·10–2·13) for NMSC and 3·04 (95% CI 1·11–6·62) for melanoma. The SMR was 0·34 (95% CI 0·16–0·65). Conclusions: AE rates remained stable in this analysis of patients with psoriasis receiving adalimumab; no new safety signals were identified compared with earlier analyses. What's already known about this topic? The long‐term safety of adalimumab has been established in > 23 000 patients in clinical trials across multiple indications.A previous comprehensive safety analysis of long‐term adalimumab clinical data for the treatment of psoriasis from 13 clinical trials demonstrated a favourable safety profile for adalimumab in psoriasis. What does this study add? Five additional adalimumab clinical trials in psoriasis have been completed since the November 2009 analysis.This comprehensive long‐term integrated analysis of adalimumab safety in 3727 patients with psoriasis enrolled in 18 clinical studies found no new safety signals and was comparable with the previous safety report.The adverse event rates remained stable and consistent with currently approved labelled indications over increased adalimumab exposure time. Linked Comment: Ryan. Br J Dermatol 2019; 180:14–15. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Abstract: Background: EGALITY was a phase III confirmatory efficacy and safety study conducted in patients with plaque‐type psoriasis as a part of totality of evidence gathered during the development of GP2015, an etanercept biosimilar. Objective: To demonstrate equivalent efficacy and comparable safety and immunogenicity of GP2015 and the etanercept originator product (ETN, Enbrel®) and evaluate effects of repeated switching between GP2015 and ETN. Results for efficacy, safety and immunogenicity during treatment period (TP) 2 (TP2) are presented pooling the two continued treatment arms (pooled continued) versus the two treatment arms with repeated switches (pooled switched). Methods: Patients (n = 531) were randomized 1:1 to self‐administer GP2015 or ETN twice‐weekly subcutaneously during TP1. Patients with a ≥50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were re‐randomized for TP2 to continue the same treatment at once‐weekly dosing or to undergo three consecutive treatment switches between GP2015 and ETN until week 30. Patients continued the last‐assigned treatment during TP2, until week 52. Results: Mean (standard deviation [SD]) PASI scores at baseline were similar in patients who underwent multiple switches compared to those with continued treatments during TP2. During TP2, PASI 50, PASI 75 and PASI 90 response rates, percent change from baseline in PASI scores and all other efficacy parameters were similar between the pooled switched and pooled continued treatment groups at all time points. The incidence of treatment‐emergent adverse events including injection site reactions was comparable between the pooled switched (36.7%) and pooled continued (34.9%) groups. None of the patients in either treatment group were positive for binding anti‐drug antibodies in TP2. Conclusion: Treatment efficacy, safety and immunogenicity were similar between the pooled continued and pooled switched treatments during TP2, indicating that there are no effects in the short term on clinical data of multiple switches between GP2015 and ETN. [ABSTRACT FROM AUTHOR]

Abstract: Background: Secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe psoriasis. However, as per study protocols, transition periods from prior psoriasis treatments of a defined minimal length were required and use of concomitant psoriasis medication was prohibited. There is therefore a lack of data on the effect of shorter transition periods and concomitant psoriasis treatment with other pharmacologically active substances on the effectiveness and safety of secukinumab in routine clinical practice. Objectives: The PROSPECT study was designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab and the duration of transition periods from prior treatments to secukinumab. Here, we report the baseline characteristics and the duration of transition period in an interim analysis of the first 805 subjects. Methods: PROSPECT is an ongoing 24‐week, single‐cohort, non‐interventional study. Subjects with moderate to severe psoriasis with a decision to receive secukinumab were included. Results: The majority of subjects were male (491/796, 61.7%), with a mean age of 47.7 years (SD 13.7). The baseline Psoriasis Area and Severity Index (PASI) was available for 92.4% (744/805) of subjects, and mean baseline PASI was 17.5 (SD 13.1); 93.4% (752/805) of subjects had signs of high disease severity. Use of concomitant treatment increased with the number of signs. Within the last 12 months prior to inclusion, 10%, 40%, and 28% of subjects had received topical, conventional systemic, or biologic treatments as their last prior psoriasis therapy, respectively, and 22% of subjects had not received any psoriasis therapy. Discontinuation of prior treatment due to adverse events was high in subjects with conventional systemic treatment (93/413, 22.5%) compared to biologic treatment (5/210, 2.4%). The median duration of the transition period was 14.0, 30.5, and 38.0 days for prior topical, conventional systemic, and biologic treatments, respectively. Conclusion: PROSPECT is the first study to investigate prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real‐world setting. The majority of the subjects had a high disease burden and use of concomitant treatment increased with disease severity. The duration of the transition period depended on prior treatment. [ABSTRACT FROM AUTHOR]

Background Secukinumab has demonstrated significant efficacy with a good safety profile through 1 year in plaque psoriasis. Given the chronic nature of this disease, long-term follow-up is needed to evaluate psoriasis therapies fully. Objectives To determine the long-term (3-year) efficacy and safety of secukinumab in moderate-to-severe psoriasis. Methods Patients completing 52 weeks of secukinumab treatment in the SCULPTURE core study entered an extension in which they continued the same double-blind regimens. Dosing regimens included a fixed-interval schedule ( FI; every 4 weeks) and retreatment as needed ( RAN), in which patients were withdrawn from secukinumab and received placebo until the start of relapse, at which time secukinumab every 4 weeks was reinitiated. The study was registered with number NCT01640951. Results In total 168 patients receiving secukinumab 300 mg FI and 172 receiving secukinumab 300 mg RAN entered the extension. Secukinumab 300 mg FI sustained high efficacy: at the end of year 3, the proportion of responders achieving ≥ 90% improvement in Psoriasis Area and Severity Index ( PASI 90) was 63·8%, and of PASI 100 responders it was 42·6%. The mean absolute PASI remained low (2-4) from week 52 to week 152 with 300 mg FI, with approximately two-thirds of patients reporting no impact of skin disease on their lives (Dermatology Life Quality Index of 0 or 1). Improvements in overall and subscale scores on all quality-of-life instruments were well sustained. As in the core study, FI dosing was consistently more efficacious than RAN. No new safety signals were identified to year 3. Conclusions Secukinumab 300 mg FI sustained high responses and improved quality of life with no new safety concerns through 3 years. [ABSTRACT FROM AUTHOR]

Background Secukinumab is a fully human antibody that neutralizes interleukin-17A. It has significant efficacy and a favourable safety profile in moderate-to-severe plaque psoriasis and psoriatic arthritis. Objectives To compare secukinumab with fumaric acid esters ( FAEs) in a randomized controlled trial. Methods In this 24-week, randomized, open-label, multicentre study with blinded assessment, patients with moderate-to-severe plaque psoriasis, naive to systemic treatments, were randomized to receive secukinumab 300 mg subcutaneously or oral FAEs. The primary end point was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score ( PASI 75 response) at week 24, and missing patients were considered responders if they were responders at the time of dropout. Results In total 202 patients were randomized and 200 were treated with at least one dose. Outcomes at week 24 were available for 147 and imputed for 53 patients. Discontinuations were mostly due to adverse events, which occurred more frequently in the FAE group (1·9% vs. 33·0%). At week 24, significantly more patients receiving secukinumab compared with FAEs achieved PASI 75 response (89·5% vs. 33·7%, P < 0·001), PASI 90 response (81·0% vs. 28·4%, P < 0·001) and Dermatology Life Quality Index 0 or 1 response (71·4% vs. 25·3%, P < 0·001). Conclusions Secukinumab demonstrated superior efficacy to FAEs in patients with psoriasis over a 24-week period. [ABSTRACT FROM AUTHOR]

Background GP2015 is a proposed etanercept biosimilar. Objectives To demonstrate equivalent efficacy, and comparable safety and immunogenicity of GP2015 and the etanercept originator ( ETN, Enbrel®) in patients with moderate-to-severe chronic plaque-type psoriasis. Methods In total, 531 eligible patients were randomized 1 : 1 to self-administer GP2015 or ETN twice weekly subcutaneously. Patients with ≥ 50% improvement in Psoriasis Area and Severity Index ( PASI 50) at week 12 were rerandomized to continue the same treatment on a once-weekly dosing schedule or to undergo a sequence of three treatment switches between GP2015 and ETN until week 30. Thereafter, patients continued treatment with the product they had been assigned to last, up to week 52. Results The difference in PASI 75 (75% improvement from baseline PASI score) response rates at week 12 between GP2015 and ETN (primary end point) was −2·3%. The 95% confidence interval (−9·85 to 5·30) was well contained within the prespecified margin range of −18 to 18. The incidence of treatment-emergent adverse events up to week 52 was comparable between continued GP2015 (59·8%) and ETN (57·3%); switching treatments revealed comparable safety profiles. Antidrug antibodies, all non-neutralizing, were limited to five patients on ETN during treatment period 1, and one patient in the switched ETN group, who had been treated with GP2015 for 12 weeks at the time of the finding. Conclusions The EGALITY study demonstrated equivalent efficacy and comparable safety and immunogenicity of GP2015 and ETN. The study results provide the final clinical confirmation of biosimilarity and contribute to the totality of the evidence proposing that GP2015 is an etanercept biosimilar. [ABSTRACT FROM AUTHOR]

Background Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis. Objectives To evaluate the impact of apremilast on health-related quality of life ( HRQOL), general functioning and mental health using patient-reported outcome ( PRO) assessments among patients with moderate to severe plaque psoriasis in the ESTEEM 1 and 2 trials. Methods A total of 1255 patients were randomized (2 : 1) to apremilast 30 mg BID or placebo for 16 weeks; all received apremilast through Week 32. PRO assessments included the Dermatology Life Quality Index ( DLQI), 36-Item Short-Form Health Survey version 2 mental/physical component summary scores ( SF-36v2 MCS/ PCS), Patient Health Questionnaire-8 ( PHQ-8), EuroQol-5D ( EQ-5D) and Work Limitations Questionnaire-25 ( WLQ-25). Post hoc analyses examined relationships between Psoriasis Area and Severity Index ( PASI) scores and PHQ-8 in the apremilast-treated population at Week 16. Results Treatment with apremilast improved all HRQOL PROs at Week 16 (vs. placebo), except the SF-36v2 PCS, and improvements were sustained through Week 32. Mean DLQI and SF-36v2 MCS improvements exceeded minimal clinically important differences. Changes at Week 16 in PHQ-8 and PASI were weakly correlated, and only 35.8% of patients who achieved a ≥75% reduction from baseline in PASI score ( PASI-75) with apremilast treatment also achieved PHQ-8 scores of 0-4. Conclusions Apremilast led to improvements in HRQOL PROs vs. placebo in patients with moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]