The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis: results from a nationwide prospective study.

To assess the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on retention to tumour necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). Data on patients with a clinical diagnosis of AS or uSpA starting treatment with adalimumab, etanercept or infliximab as their first TNFi during 2003-2010 were retrieved from the Swedish national biologics register and linked to national population based registers. Five-year drug survival was analysed by Cox regression with age, sex, baseline csDMARD comedication, TNFi type, prescription year and covariates representing frailty and socioeconomic status. AS and uSpA were analysed separately. Sensitivity analyses included models with csDMARD as a time-dependent covariate and adjustments for additional potential confounders. 1365 patients with AS and 1155 patients with uSpA were included, of whom 40.8% versus 50.3% used csDMARD comedication at baseline. In the unadjusted analyses superior drug survival was observed for patients using versus not using csDMARD comedication among patients with AS (p<0.001) but not among patients with uSpA (p=0.175). In the multivariable Cox regression analyses comedication with csDMARD was associated with better retention to TNFi therapy both in AS (HR 0.71, p<0.001) and uSpA (HR 0.82, p=0.020). The results were similar with csDMARD comedication as a time-dependent covariate, and the associations were retained when adjusting for erythrocyte sedimentation rate, C-reactive protein, patient global, swollen joints, uveitis, psoriasis and inflammatory bowel disease. In this large register study of patients with AS and uSpA, use of csDMARD comedication was associated with better 5-year retention to the first TNFi.

Lie E ，Kristensen LE ，Forsblad-d'Elia H ，Zverkova-Sandström T ，Askling J ，Jacobsson LT ，ARTIS Study Group ... -  《-》

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

Lindström U ，Di Giuseppe D ，Delcoigne B ，Glintborg B ，Möller B ，Ciurea A ，Pombo-Suarez M ，Sanchez-Piedra C ，Eklund K ，Relas H ，Gudbjornsson B ，Love TJ ，Jones GT ，Codreanu C ，Ionescu R ，Nekvindova L ，Závada J ，Atas N ，Yolbas S ，Fagerli KM ，Michelsen B ，Rotar Ž ，Tomšič M ，Iannone F ，Santos MJ ，Avila-Ribeiro P ，Ørnbjerg LM ，Østergaard M ，Jacobsson LT ，Askling J ，Nissen MJ ... -  《-》

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.

Lie E ，van der Heijde D ，Uhlig T ，Mikkelsen K ，Rødevand E ，Koldingsnes W ，Kaufmann C ，Kvien TK ... -  《-》

Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis.

This meta-analysis investigates the efficacy of tumour necrosis factor α (TNFα) blockers versus placebo for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). A systematic literature search was conducted independently by two reviewers. Double-blind randomised controlled trials (RCTs) investigating the efficacy of adalimumab, certolizumab, etanercept, golimumab or infliximab in approved dosages in comparison with placebo were included. The use of concomitant non-steroidal antirheumatic drugs was allowed. The outcome parameters were improvement in disease activity and function measured by the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and ASAS40 response. The effect sizes of the changes in BASDAI/BASFI between TNFα blocker and placebo comparator groups were calculated. Mixed effect models were applied separately for RCTs with AS and nr-axSpA patients and differences between those groups were evaluated in a joint model. 20 studies with data from 3096 patients were included in the analysis: 15 studies with AS patients, four with nr-axSpA patients and one with both. For AS patients, TNFα blockers showed better efficacy than placebo for BASDAI (effect size 1.00), BASFI (effect size 0.67) and ASAS40 response (OR 4.7). For nr-axSpA patients, the differences were smaller (effect sizes 0.73, 0.57; OR 3.6). However, after adjustment for the year of publication as a proxy for disease severity, no differences in the effect sizes between the AS and nr-axSpA trials were observed. Compared with placebo, TNFα blockers improve disease activity and functional capacity clinically meaningful for both AS and nr-axSpA patients.

Callhoff J ，Sieper J ，Weiß A ，Zink A ，Listing J ... -  《-》

The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study.

Fagerli KM ，Lie E ，van der Heijde D ，Heiberg MS ，Lexberg AS ，Rødevand E ，Kalstad S ，Mikkelsen K ，Kvien TK ... -  《-》