Tumor necrosis factor (TNF) inhibitors for psoriatic arthritis.

Abstract

Background: 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.

Objectives: To assess the benefits and harms of TNFi in adults with psoriatic arthritis.

Search methods: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization trials portal up to 28 March 2024.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.

Authors' conclusions: 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.