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Objectives To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. Methods In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan–Meier analysis for time to resolution, and as-observed data for other outcomes. Results Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. Conclusion Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. Trial registration ClinicalTrials.gov , NCT02745080 [ABSTRACT FROM AUTHOR]

Objective We investigated the impact of concomitant MTX on ustekinumab (UST) levels and antidrug antibody (ADA) formation in PsA and evaluated consequences in pharmacodynamics and pharmacokinetics. Methods We conducted a post-hoc analysis on 112 PsA serum samples of subjects treated with open-label UST and either concomitant MTX (UST/MTX, n  = 58) or placebo (UST/pbo, n  = 54) obtained in a randomized (1:1), double-blind, multicentre trial. A validated antibody-binding-based multitiered testing was used to detect ADA and ADA with neutralizing capacity (nADA). The impact of MTX on UST immunogenicity was analysed by comparison of UST/pbo with UST/MTX cohorts at different time points. Patient- and disease-related predispositions for ADA formation were investigated with multiple linear regression analysis. Immunogenicity impact on pharmacokinetics, safety and efficacy was determined by cohort comparison between patients with and without ADA formation. Results Over 52 weeks, 11 UST/pbo- and 19 UST/MTX-treated patients developed ADA (P  > 0.05). In the UST/pbo cohort, the visit-dependent UST levels were in the range of 0.047 (0.05) –0.110 (0.07) µg/ml overall, and 0.037 (0.04)–0.091 (0.08) µg/ml in ADA-confirmed subjects. In UST/MTX-treated patients, the UST levels exhibited an intervisit variation in the range of 0.0502 (0.04)–0.106 (0.07) µg/ml overall and 0.029 (0.03)–0.097 (0.07) µg/ml in ADA positive subjects (P  > 0.05). At week 52, ADA-confirmed patients did not differ significantly (P  > 0.05) in safety or clinical outcomes from ADA-negative patients. Conclusion Concomitant MTX had no significant impact on UST immunogenicity. Furthermore, ADA formation was not associated with impairments in UST safety, efficacy or trough levels. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03148860. [ABSTRACT FROM AUTHOR]

Objective PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. Methods KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208. Results At week 24, 57.3% of risankizumab-treated patients (n  =   483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n  =   481; P  < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52. Conclusion In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , KEEPsAKE1, NCT03675308. [ABSTRACT FROM AUTHOR]

Objectives PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial. Methods Adult patients with active PsA (n  = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment–PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo. Results At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P  < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P  < 0.01). Conclusion Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03675308 [ABSTRACT FROM AUTHOR]

Objective ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients. Methods Patients ≥18 years (n  = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab. Results At week 24, a higher, yet statistically non-significant (P  = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (−2.8 [3.0] vs −1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes. Conclusion A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes. Trial registration clinicaltrials.gov, NCT02771210 [ABSTRACT FROM AUTHOR]

Current EULAR guidelines state that biologic DMARD (bDMARD) therapy should be administered in combination with MTX or other conventional synthetic (cs) DMARD in RA. Nonetheless, a third of patients for whom a bDMARD agent is prescribed take it in the absence of concurrent csDMARD therapy. While the reasons underlying the low uptake of bDMARD-csDMARD combination therapy in clinical practice have not been well delineated, they may include poor adherence, contraindication to csDMARD therapy and adverse effects, as well as csDMARD withdrawal following remission. The challenges surrounding bDMARD therapy and the benefit/risk ratio of biologic monotherapy when compared with combination with a csDMARD will be discussed. We will provide insights into these important issues, as well as reviewing the evidence base differentiating biologic agents and exploring therapeutic options for patients with rheumatoid arthritis for whom csDMARD therapy is contraindicated or discontinued. [ABSTRACT FROM AUTHOR]