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This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as “existing use” starting before registry entry or “initiated use” starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with

Introduction Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. Methods This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. Results A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference − 4 mm; 95% confidence interval: − 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. Conclusions The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. Trial Registration ClinicalTrials.gov: NCT02986139. Funding Amgen Inc, Thousand Oaks, CA USA.

Response to etanercept therapy in patients who have failed apremilast therapy has not been well characterized.In this multicenter, open-label, single-arm, phase 4, estimation study, subjects with moderate to severe plaque psoriasis received etanercept 50 mg SC twice weekly for 12 weeks, followed by etanercept 50 mg SC once weekly for an additional 12 weeks. Subjects had BSA greater than equal to 10%, PASI greater than equal to 10, and sPGA greater than equal to 3 at screening and baseline; and had failed apremilast-because of either failure to achieve or loss of adequate clinical response, or intolerability to apremilast in the opinion of the investigator. Primary endpoint was PASI 75 at week 12. Secondary endpoints included PASI 75 at week 24, PASI 90 at weeks 12 and 24, and patient-reported outcomes: Psoriasis Symptom Inventory (PSI) score (total and individual items) at baseline and weeks 12 and 24, and over time; DLQI responder analysis (5-point improvement in DLQI from baseline or score of 0) at weeks 12 and 24; and patient assessment of treatment satisfaction at baseline and weeks 12 and 24.Among 80 patients, PASI 75 at weeks 12 and 24 was 41.6% (95% CI, 30.4%-53.4%) and 45.5% (34.1%-57.1%), respectively; PASI 90 was 13.0% (6.4%-22.6%) and 22.1% (13.4%-33.0%), respectively. Mean total PSI score (LOCF) improved from 16.6 (95% CI, 15.1-18.0) at baseline to 8.8 (7.3-10.2) and 9.6 (7.9-11.4) at weeks 12 and 24, respectively; improvements in item PSI scores were similar. The percentage of DLQI responders was 66.2% (95% CI, 54.3%-76.8%) and 57.3% (45.4%-68.7%) at weeks 12 and 24, respectively. The percentage of subjects who were satisfied/very satisfied with their psoriasis treatment improved from 5.0% at baseline to 60.8% and 53.3% at weeks 12 and 24, respectively. During the 24-week study, 23.8% and 2.5% of subjects reported an adverse event and serious adverse event, respectively; there were no new safety signals in this study.In patients who have failed apremilast, etanercept may represent an effective therapeutic option.ClinicalTrials.gov: NCT02749370 J Drugs Dermatol. 2018;17(10):1078-1082.

Background Until recently, treatment for moderate to severe psoriatic arthritis (PsA) mainly focused on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumour necrosis factor inhibitors (TNFis). However, the persistence of TNFis alone or in combination with csDMARDs is not well understood. Objectives To assess real-word treatment patterns among patients with PsA receiving TNFi monotherapy, csDMARD monotherapy, or TNFi and csDMARD combination therapy. Methods This retrospective study utilised data from patients with PsA aged ≥18 years, enrolled in the Corrona PsA registry between March 21, 2013, and July 31, 2017, treated with a TNFi and/or csDMARD (index therapy), and with ≥6 months of follow-up time. Patients were stratified by prevalent (initiation before enrollment) or incident (initiation after enrollment) therapy use; cohorts were based on index therapy: TNFi monotherapy, csDMARD monotherapy, or combination therapy. Outcomes of interest were the percentage of patients who were persistent on their index therapy or had a therapy change (discontinued, switched, or restarted) 12 months after the index visit. Results There were 1266 patients in this study: 1144 prevalent and 122 incident (table 1). Patient characteristics at the index date were similar among patients; however, csDMARD monotherapy patients had higher disease activity than either TNFi group. Among prevalent patients, TNFi monotherapy patients were likely to be female (59%) and younger (51.9 years), nearly all patients had psoriasis, and BSA was similar and ≤5. At month 12, among patients with a follow-up visit within the 9–15–month window, the vast majority of prevalent patients and half of incident patients were persistent on their index therapy, and one quarter to one third of incident patients discontinued or switched therapy (table 1). Conclusions Most patients who were prevalent on therapy at the time of enrollment in Corrona remained persistent on their therapy for 12 months in this study, while roughly half of patients initiating therapy after enrollment remained persistent over the same period. Young, female patients were more likely to receive TNFi monotherapy; the TNFi monotherapy cohort was associated with the least disease activity. The incident group was not different from the prevalent group. Although the prevalent group is more likely to have patients who responded to treatment, the data suggest that most therapy changes occur within the first year of PsA treatment. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, and UCB, N. Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Rebello Employee of: Corrona LLC, C. Etzel Consultant for: Merck, Employee of: Corrona LLC, R. Harrison Employee of: Corrona LLC, G. Aras Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. Gharaibeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., J. Greenberg Shareholder of: Corrona LLC, Consultant for: Genentech, Janssen, Novartis, Pfizer, and Eli Lilly, Employee of: Corrona LLC, D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Background PsA patients have greater prevalence of cardiovascular disease (CVD), metabolic syndrome (MetS), and cancer than patients without PsA. Objectives To examine patient characteristics and disease activity by comorbidity profile among PsA patients. Methods This analysis included adults with PsA enrolled in the US Corrona PsA/spondyloarthritis Registry from March 2013-March 2017 and followed for ≥6 months. Prevalence (at registry entry) and incidence rate (time to new events after registry entry) of CVD, MetS, and cancer were determined. Patient characteristics and disease activity were described by prevalent comorbidity, with t-tests for means despite skewed data and chi-squared tests for percentages. Results The analysis included 1493 patients and 3564 patient-years of follow-up. Incidences (95% confidence interval) per 1000 patient-years were 9.4 (6.5–13.5), 1.0 (0.3–3.1), and 11.4 (8.2–15.8) for CVD, MetS, and cancer (6.8 [4.5–10.2] nonmelanoma skin cancer), respectively. PsA patients with (vs without) prevalent CVD, MetS, or cancer were older, and fewer had full-time jobs or private insurance. Patients with (vs without) CVD had higher swollen joint count and mean body surface area, and tended to have higher rates of obesity. Patients with (vs without) MetS tended to have greater disease activity. Patients with (vs without) comorbidities reported less disease activity on patient global assessment. Data are mean or% a≥3 of 4 conditions: hypertension, hyperlipidemia, diabetes mellitus, or obesity bP value across all categories for employment or body mass index Conclusions PsA patients with (vs without) CVD had greater disease activity and those with (vs without) MetS tended to have greater disease activity by physician-derived measures, but PsA patients with (vs without) CVD or MetS reported lower global assessment of disease activity. Patient perception of PsA may mask the effect of comorbid CVD or MetS on disease activity. Acknowledgements Amgen Inc. supported this work. Corrona has been supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Crescendo, Eli Lilly and Company, Genentech, GSK, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer, Roche, and UCB. Jonathan Latham (PharmaScribe) and Linda Rice (Amgen) provided medical writing support. Disclosure of Interest P. Mease Grant/research support from: Abbvie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Consultant for: Abbvie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, Sun, UCB, Zynerba, Speakers bureau: Abbvie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Novartis, Pfizer, UCB, H. Litman Employee of: Corrona, LLC, N. Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Rebello Employee of: Corrona, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Genentech, Janssen, Pfizer, Eli Lilly, Novartis, Employee of: Corrona, LLC, H. Feng Employee of: Corrona, LLC, M. Gharaibeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., G. Aras Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Etanercept has been recently approved in the United States for the treatment of moderate to severe plaque psoriasis in patients aged 4-17 years. The objective of this study was to characterize etanercept pharmacokinetics, immunogenicity, and efficacy in pediatric patients. Data from a phase 3 study and open-label extension study were analyzed. Etanercept serum concentrations in pediatric patients receiving etanercept 0.8 mg/kg (maximum, 50 mg) weekly were compared with adult psoriasis patients and pediatric patients with juvenile idiopathic arthritis (JIA) who received etanercept 0.4 mg/kg twice weekly. The developments of antietanercept antibodies and efficacy based on the Psoriasis Area and Severity Index were evaluated. Steady-state trough etanercept concentrations were similar across visits from weeks 12-48, between patients aged 4-11 and 12-17 years, between pediatric and adult psoriasis patients, and between pediatric patients with psoriasis or JIA. Etanercept serum concentrations and safety profiles were similar in patients with (15.9%) and without antietanercept antibodies. Dosing used in the study provided similar exposures and efficacy across ranges of weight and body mass index. Pharmacokinetic, immunogenicity, and efficacy data support 0.8 mg/kg (maximum, 50 mg) weekly dosing of etanercept in patients aged 4-17 years.

The objective of this study is to characterize stability and clinical features of patients with rheumatoid arthritis (RA) in sustained remission. Combination therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has increased remission rates in RA but optimal regimens to maintain remission are unknown. We describe Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run-in period of longitudinal observation. Patients in Simplified Disease Activity Index (SDAI) remission (score ≤ 3.3) receiving etanercept and methotrexate were screened and had to maintain remission over 3 run-in visits/24 weeks before randomization to combination therapy or withdrawal of etanercept or methotrexate. Baseline characteristics were examined for predictive factors for maintaining remission. As of November 2016, 141 patients have enrolled; of these, 64 have been randomized, 34 were ineligible after run-in, and 43 are in run-in period; 70% have completed run-in. Enrolled and randomized patients, respectively, had mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years; mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD) methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores 1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission based on 28 joints and 66/68 joints, respectively. No enrollment characteristic predicted successful completion of run-in. Two-thirds of patients considered to be in remission at enrollment sustained remission through 24 weeks. Baseline characteristics of enrolled patients and those who completed run-in were comparable. Electronic supplementary material The online version of this article (10.1007/s10067-017-3923-z) contains supplementary material, which is available to authorized users.

In long-term single cohort safety studies, the incremental incidence rate is a useful concept in evaluating risks related to adverse events of medical interest (EMI). We propose estimates for the incremental (say annual) incidence rates in the presence of independent random right censoring and describe their statistical properties. More importantly, we propose tests for the null hypothesis that the incremental incidence rates remain constant during the study against various alternative hypotheses, such as rates changing over the years or having a specific trend, say monotonic increasing or decreasing. In contrast with the existing methods that test constant hazard rates, the proposed method allows nonconstant hazard within each year; therefore, it is especially useful for EMIs that have a seasonal occurrence pattern. This article explores and characterizes properties of these tests under various alternatives via theory and simulations. A numerical example based on a real long-term single cohort safety stu...

Background Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults. Objective We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective. Methods OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period. Results A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database. Limitations The registry lacks a control group, and the study is too small to measure the frequency of rare events. Conclusion Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

Background In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti–interleukin-17–receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis. Methods We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12. Results A total of 198 patients underwent randomization. At week 12, the mean percentage improvem...

Tukey, Ciminera, and Heyse (1985) proposed a linear trend test to establish a dose response; or if used sequentially, by eliminating the highest dose at each stage, to select the no-statistical-significance-of-trend (NOSTASOT) dose. The traditional alternatives have been to test the highest dose versus the control, ignoring contributions from the middle doses; or its sequential analog, to establish a minimum effective dose by testing first the highest dose versus the control, and if significant, testing the subsequent doses against the contrast until no significance is observed or doses are exhausted. In dose-response trials and/or in dose-finding trials, clinicians may believe a priori that the ordering of the responses is known, so the efficacy is assumed to increase monotonically with dose. Under order restricted alternatives, that is, under monotonic dose-response assumption, it is generally believed that Tukey’s contrast test, an analog of Tukey’s linear trend test in an analysis of variance set up, ...

Objectives o evaluate the efficacy of etanercept and methotrexate as monotherapies and as combination therapy in subjects with active psoriatic arthritis (PsA). Methods he Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) is an ongoing, global, doubleblind, 48-week, randomised, controlled study. Subjects are randomised (1:1:1) to etanercept monotherapy, methotrexate monotherapy or etanercept-methotrexate combination therapy. Endpoints include rates of ACR20 response and Minimal Disease Activity, measures to characterise extra-articular manifestations (dactylitis, enthesitis, nail disease) and safety. Conclusion SEAM-PsA will characterise the effects of etanercept with and without background methotrexate and methotrexate alone on PsA manifestations, and provide information of practical importance to clinicians on the optimal treatment of PsA.

Background OBSERVE-5 was a 5-year Food and Drug Administration–mandated surveillance registry of patients with psoriasis. Objective We sought to assess long-term etanercept safety and effectiveness. Methods Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database. Results For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. Limitations No internal comparator group was included; rare events may not have been detected. Conclusion No new safety signals were observed with long-term, real-world etanercept use.