Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis.

OBJECTIVES: To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA. METHODS: All patients with PsA starting secukinumab or a TNFi in 2015-2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+). RESULTS: We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar. CONCLUSION: No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis.

Objectives: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA. Methods: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Results: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates. Conclusion: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. Systematic review registration number: PROSPERO CRD42014014842.

Association of exercise therapy and reduction of pain sensitivity in patients with knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: Exercise has beneficial effects on pain in knee osteoarthritis (OA), yet the underlying mechanisms are unclear. The purpose of this study was to investigate the effects of exercise on pressure-pain sensitivity in patients with knee OA. METHODS: In a randomized controlled trial, participants were assigned to 12 weeks of supervised exercise therapy (ET; 36 sessions) or a no attention control group (CG). Pressure-pain sensitivity was assessed by cuff pressure algometry on the calf of the most symptomatic leg. The coprimary outcomes were pressure-pain thresholds (PPTs) and cumulated visual analog scale pain scores during constant pressure for 6 minutes at 125% of the PPT as a measure of temporal summation (TS) of pressure-pain. Secondary outcomes included self-reported pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Analyses were based on the "per-protocol" population (participants following the protocol). RESULTS: Sixty participants were randomized (31 in ET group, 29 in CG), and the per-protocol population included 48 participants (25 in ET group, 23 in CG). At followup, mean group differences in the change from baseline were 3.1 kPa (95% confidence interval [95% CI] 0.2, 6.0; P = 0.038) for the PPT, 2,608 mm × seconds (95% CI 458, 4,758; P = 0.019) for TS, and 6.8 points (95% CI 1.2, 12.4; P = 0.018) for KOOS pain, all in favor of ET. CONCLUSION: Pressure-pain sensitivity, TS, and self-reported pain are reduced among patients completing a 12-week supervised exercise program compared to a no attention CG. These results demonstrate beneficial effects of exercise on basic pain mechanisms and further exploration may provide a basis for optimized treatment.