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. Supplementary Information The online version contains supplementary material available at 10.1007/s10067-021-05743-2.

Novel Th17 Lymphocyte Populations, Th17.1 and PD1+Th17, are Increased in Takayasu Arteritis, and Both Th17 and Th17.1 Sub-Populations Associate with Active Disease

“… 47 , 48 Based on observational studies, anti-tumor necrosis factor-alpha (anti-TNF) agents and tocilizumab achieve clinical response in nearly three-fourth patients, although their effect on angiographic stabilization is less defined. 49 Sub-optimal angiographic response with currently used immunosuppressive therapies in TAK lends credence to the hypothesis that adding an anti-fibrotic therapy to immunosuppressive therapy might favorably modulate vascular remodeling by reducing fibrosis consequent to inflammation-associated vascular injury. Costly biological therapies are inaccessible in vast swathes of the globe including India.…”

Novel Therapies in Takayasu Arteritis

“…Cohort studies have showed that methotrexate ( 45 ), azathioprine ( 46 ), mycophenolate mofetil ( 47 ), leflunomide ( 48 ) and cyclophosphamide ( 49 ) could improve clinical and radiological manifestations of TAK and have a GC-sparing effect. However, there are no randomized trials comparing the efficacy of different csDMARDs, and two recent meta-analysis on csDMARDs in TAK indicated similar efficacy rates between these drugs ( 25 , 50 ). Therefore, clinical practice typically reflects the results of these low level of evidence data and expert opinion.…”

“…A recent meta-analysis by Misra et al ( 25 ) analyzed 19 observational studies on TNFi in TAK, showing that more than 80% of treated patients attained at least partial clinical response, angiographic stabilization, improvement in PET-CT and normalization of inflammatory markers. Relapse rate was estimated as 32% but with considerable heterogeneity across studies.…”

“…The above-mentioned meta-analysis performed by Misra et al ( 25 ) included 22 observational studies on tocilizumab in TAK patients. Pooling data from these studies, authors described tocilizumab effective in attaining at least a partial clinical response in 87% patients although the results were heterogenous among studies.…”

Patient-Reported Outcome Measures in Takayasu Arteritis: A Systematic Review and Meta-Analysis

“…Studies reporting PROMs in TAK (both adultonset [18][19][20][21] and childhood-onset [22] forms) reporting original data on any PROM were included. Due to the paucity of randomized controlled trials (RCTs) in TAK [23], both RCTs and observational studies (with or without control group) were included. Review articles, case reports, editorials and letters to editors were excluded.…”