Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis-a systematic review and meta-analysis

Abstract

The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK.

Keywords: Anti-rheumatic drugs; Aortoarteritis; Biological drugs; Disease-modifying systematic review; Meta-analysis; Takayasu arteritis.

Fig. 1

Search results (adapted from the PRISMA flow diagram [13])

Fig. 2

Forest plot for proportions of patients with Takayasu arteritis (TAK) with at least a partial clinical response from observational studies. 95% CI 95% confidence intervals, ES effect size, TNFi tumour necrosis factor alpha inhibitors

Fig. 3

Forest plot for proportions of patients with Takayasu arteritis (TAK) with angiographic stabilization from observational studies. 95% CI 95% confidence intervals, ES effect size, TNFi tumour necrosis factor alpha inhibitors

Fig. 4

Forest plot for proportions of patients with Takayasu arteritis (TAK) from observational studies with a improvement on PET-CT, b normalization of inflammatory markers and c relapses. 95% CI 95% confidence intervals, CRP C-reactive protein, ES effect size, ESR erythrocyte sedimentation rate, PET-CT positron emission tomography computerized tomography, TNFi tumour necrosis factor alpha inhibitors