Background Large vessel vasculitis (LVV) includes two major variants with similar histopathology - giant cell arteritis (GCA) and Takayasu’s arteritis (TAA). High dose glucocorticoids are the mainstay for treatment; however, many patients remain on high doses of steroids for prolonged periods, and are at risk for developing complications. Anti-cytokine/immune cell monoclonal antibodies (biological agents) are used to manage patients with GCA and TA that are refractory to glucocorticoid therapy; however their efficacy is unclear.
Objectives To conduct a systematic review (1) to assess the effectiveness and safety of biological agents (infliximab (IFX), adalimumab (ADA), etanercept (ETN), rituximab, ustekinumab, abatacept and tocilizumab (TCZ)) in the management of patients with LVV. Our primary outcomes were the induction of remission and the dose reduction of concurrent corticosteroids to <10 mg/d.
Methods A medical librarian searched MEDLINE, Embase, Web of Knowledge, Proquest Dissertations and Theses, and Evidence Based Medicine Reviews up to October 2012. We hand searched conference proceedings from EULAR and the ACR (2009 – 2012). Two reviewers independently selected studies, assessed methodological quality, and extracted data. Included studies were randomized control trials (RCTs), prospective or retrospective cohort studies, or case series (≥ 2 patients) where biological agents were used to treat patients with LVV. Study quality was assessed using the Oxford method for RCTs and the Newcastle Ottawa scale for observational studies.
Results We identified 3326 articles; 24 studies were included in our final analysis (3 RCTs, 5 cohort studies, 16 case series). Overall, a total of 95 GCA and 116 TAA patients received biological agents. All of the GCA patients (n = 19) and 82% of TAA patients (n = 9/11) treated with TCZ achieved both remission and reduction of corticosteroid dosage. From the RCTs for GCA patients receiving an anti-TNF agent (n = 28/44 IFX, 8/17 ETN, 34/70 ADA patients, respectively), none achieved and maintained remission in a statistically significant manner. On the other hand, 57% (48/84) of patients with refractory TAA treated with IFX achieved sustained remission as defined by each study. The quality of the studies was good to fair. The main areas of concern include selection bias for the observational studies, variable and inadequate follow-up periods for patients while in remission, and a variable definition for disease remission.
Conclusions Our results suggest that TCZ may be effective in inducing remission and reducing corticosteroid doses in patients with glucocorticoid-dependent TAA and GCA. IFX might be effective in treating patients with refractory TAA. Future studies defining remission as clinical, serological (ESR, CRP, IL-6), and radiographic disease control are necessary in further establishing a role for these agents in the treatment of LVV and the reduction of glucocorticoids.
PROSPERO, International prospective register for systematic reviews.
Disclosure of Interest None Declared