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 ... -  《-》

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 ... -  《-》

Tumor necrosis factor (TNF) inhibitors for psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic arthritis affecting people with psoriasis. If untreated, it may lead to disability. Recommended drugs are non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). Tumour necrosis factor inhibitors (TNFi) are the first choice bDMARDs. To assess the benefits and harms of TNFi in adults with psoriatic arthritis. We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization trials portal up to 28 March 2024. We included randomized controlled trials (RCTs) in adults with PsA, comparing TNFi to placebo, physiotherapy, NSAIDs, corticosteroids, and cs/b/tsDMARDs. Major outcomes included clinical improvement, minimal disease activity, physical function, health-related quality of life, radiographic progression, serious adverse events, and withdrawals due to adverse events. We used standard Cochrane methods. The primary comparison was TNFi versus placebo. The primary time point was 12 weeks for clinical improvement; 24 weeks for minimal disease activity, function, quality of life, and radiographic progression; and the end of the trial period for serious adverse events and withdrawals due to adverse events. We included 25 RCTs randomizing 7857 participants. Four studies compared TNFi to methotrexate and one to ustekinumab in DMARD-naïve participants. In csDMARD-inadequate responders, 11 studies compared TNFi to placebo; four studies compared TNFi to placebo and ixekizumab, bimekizumab, tofacitinib, or upadacitinib; and three studies compared TNFi to ixekizumab, secukinumab, and ustekinumab. Two studies compared different TNFi. We found no studies with b/tsDMARD-inadequate responders (b/tsDMARD-IR). No studies compared TNFi to NSAIDs, corticosteroids, or physiotherapy. Performance (32%), detection (56%) and reporting (80%) biases were at high or unclear risk across studies. Only one study had a low risk of bias in all domains. We limit reporting to the primary comparison, TNFi versus placebo. DMARD-naïve We found no studies comparing TNFi with placebo in DMARD-naïve participants. csDMARD-inadequate responders TNFi probably result in a large clinical improvement compared to placebo. At 12 weeks, 149/1926 (8%) participants in the placebo group showed a clinical improvement (ACR50) compared to 784/2141 (37%) participants in the TNFi group (risk ratio (RR) 5.63, 95% confidence interval (CI) 3.98 to 7.96; I2 = 65%; 14 studies, 4067 participants; moderate-certainty evidence). TNFi probably result in a higher proportion of participants in minimal disease activity. At 24 weeks, 95/1017 (9%) participants in the placebo group were in minimal disease activity compared to 428/1336 (32%) participants in the TNFi group (RR 3.76, 95% CI 2.39 to 5.92; I2 = 72%; 5 studies, 2353 participants; moderate-certainty evidence). At 24 weeks, TNFi may improve function compared to placebo. The mean change in function from baseline (assessed with the Health Assessment Questionnaire; score from 0 to 3, 0 = no disability; minimal clinically important difference (MCID) = 0.35) was -0.14 points with placebo and 0.33 points lower (0.41 lower to 0.25 lower) with TNFi (I2 = 72%; 8 studies, 2949 participants; low-certainty evidence). TNFi probably result in a clinically important improvement in health-related quality of life. The mean change in quality of life from baseline (assessed with the Short Form 36-item Mental Component Summary questionnaire; score from 0 to 100, 100 = best score; MCID = 1.7) was 2.4 points with placebo and 3.29 points higher (2.18 points higher to 4.40 points higher) with TNFi (I2 = 52%; 8 studies, 2928 participants; moderate-certainty evidence). TNFi probably slightly reduce radiographic progression. The mean change in radiographic progression (assessed with the Sharp/Van der Heijde-PsA score; scale from 0 to 528, 0 = no damage) was 0.25 points with placebo and 0.37 points lower with TNFi (0.48 lower to 0.25 lower) (I2 = 32%; 7 studies, 2478 participants; moderate-certainty evidence) at 24 weeks. We downgraded the evidence to moderate certainty for clinical improvement, minimal disease activity, quality of life, and radiographic progression due to risk of bias. For function, we downgraded the evidence to low certainty for risk of bias and imprecision. TNFi may result in little to no difference in serious adverse events, but may slightly increase withdrawals due to adverse events, compared to placebo. At the end of follow-up: 56/1826 participants (3%) given placebo and 69/1900 (4%) participants given TNFi experienced serious adverse events (RR 1.00, 95% CI 0.70 to 1.42; I2 = 0%; 13 studies, 3866 participants; low-certainty evidence); and 35/1926 (2%) participants given placebo and 65/2140 (3%) given TNFi withdrew due to adverse events (RR 1.53, 95% CI 1.01 to 2.33; I2 = 0%; 14 studies, 4066 participants; low-certainty evidence). We downgraded the evidence to low certainty for risk of bias and imprecision. In csDMARD-inadequate responders, moderate-certainty evidence showed that TNFi probably result in a large clinical improvement, lower disease activity, small decrease in radiographic progression, and better quality of life compared to placebo. Low-certainty evidence showed that TNFi may lead to a slight improvement in physical function compared to placebo. Low-certainty evidence suggested that TNFi may lead to a slight increase in withdrawals due to adverse events, whereas they may result in little to no difference in serious adverse events compared to placebo. No trials assessed TNFi compared to placebo in DMARD-naïve participants or in b/tsDMARD-IR.

Cagnotto G ，Bruschettini M ，Stróżyk A ，Scirè CA ，Compagno M ... -  《Cochrane Database of Systematic Reviews》

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 ... -  《-》

Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifyin

To compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD). We included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data. The proportions of CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction. 771 patients on TCZ as monotherapy (TCZ mono), 1773 in combination therapy (TCZ combo), 1404 on TNFi as monotherapy (TNFi mono) and 4660 in combination therapy (TNFi combo) were retrieved. Crude median retention was higher for TCZ mono (2.31 years, 95% CI 2.07 to 2.61) and TCZ combo (1.98 years, 95% CI 1.83 to 2.11) than TNFi combo (1.37 years, 95% CI 1.30 to 1.45) and TNFi mono (1.31 years, 95% CI 1.18 to 1.47). In a country and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were significantly lower among patients on TCZ mono or combo compared with patients on TNFi mono or combo, and TNFi combo compared with TNFi mono, but similar between TCZ mono and combo. Average adjusted CDAI change was similar between groups. CDAI remission and LDA rates were comparable between groups. With significantly longer drug retention and similar efficacy to TNFi combo, TCZ mono or combo are reasonable therapeutic options in patients with inadequate response to at least one bDMARD.

Lauper K ，Nordström DC ，Pavelka K ，Hernández MV ，Kvien TK ，Kristianslund EK ，Santos MJ ，Rotar Ž ，Iannone F ，Codreanu C ，Lukina G ，Gale SL ，Sarsour K ，Luder Y ，Courvoisier DS ，Gabay C ... -  《-》