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.
In this narrative review, we overview the recent literature on enthesitis-related arthritis (ERA). For the purpose of our review, we searched Scopus for recent articles on this subject from 2013 onward, including some classic older articles for perspective. ERA is a juvenile idiopathic arthritis (JIA) subtype more common in males, associated in a majority with human leucocyte antigen B27. Such children generally present with asymmetric oligoarthritis or polyarthritis, predominantly of lower limb joints, associated with enthesitis or sacroiliitis. While diagnosis remains clinical, ultrasound is being increasingly used to detect subclinical enthesitis and for guiding entheseal site injections. Spine MRI can help detect sacroiliitis, inflammatory spinal changes, and pelvic sites of enthesitis in such patients. The recent juvenile spondyloarthropathy disease activity index recognizes the key clinical features of ERA, viz enthesitis and inflammatory back pain, which other disease activity indices used in JIA did not include. Management includes NSAIDs with physical therapy. Conventional disease-modifying agents like sulfasalazine and methotrexate may be used to minimize duration of NSAID use and in those with high inflammatory burden. In patients refractory to these drugs, biologics such as antitumor necrosis factor alpha agents have proven useful, based on evidences from randomized controlled trials and retrospective registry analyses. Factors predicting a poorer outcome in such children include hip or ankle involvement or restricted spinal mobility. Considering that children with ERA have overall poorer long-term outcomes than other subtypes of JIA, there is a need to further optimize therapeutic strategies for such patients.
Introduction: We conducted a systematic review of patient-reported outcome measures (PROMs) regarding quality of life, disability, mood abnormalities (anxiety, depression), fatigue, illness perceptions and fibromyalgia in Takayasu arteritis (TAK). Wherever available, comparisons with healthy controls, disease controls or longitudinal changes in PROMs were noted. Methods: MEDLINE, EMBASE, Scopus, Web of Science and Pubmed Central databases, major recent international rheumatology conference abstracts, clinical trial databases and the Cochrane library were searched for relevant articles. Wherever possible, outcome measures across studies were pooled using the restricted maximum likelihood model. Inter-group differences were pooled and compared using standardized mean differences (SMD) with 95% confidence intervals (95% CI). Heterogeneity was assessed using the I 2 statistic. Quality of randomized controlled trials was assessed using the Cochrane risk of bias tool. For cross-sectional and cohort studies, the Joana Briggs Institute checklist and Newcastle-Ottawa scale were used, respectively. GRADE methodology was used to determine the certainty of evidence for outcomes. Results: Twenty-one studies (all but one observational) involving 1311 patients with TAK and 308 healthy controls were identified. Ten studies (559 TAK patients, 182 healthy controls were synthesized in a meta-analysis. Patients with TAK had worse quality of life (pooled SMD -6.66, 95% CI -10.08 to -3.23 for individual domains; -0.64, 95% CI -1.19 to -0.09 for pooled physical and mental component scores of 36-item Short Form Survey), depression (SMD 0.26, 95% 0.05-0.47) and anxiety (SMD 0.34, 95% CI -0.06 to 0.75) Durga P. Misra and Upendra Rathore are joint first authors.
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