Background Remission in ANCA-associated vasculitides (AAV) is achieved traditionally using glucocorticosteroids (GCS) and cyclophosphamide (CYC), followed by azathioprine (AZA) for maintenance therapy. Patients still experience a high relapse and remission failure rate whilst receiving these drugs. This regimen of treatment has also been linked to a substantial amount of cumulative toxicity giving rise to adverse effects. Recently there has been evidence that Rituximab (RTX) can be considered as an alternative drug for both remission induction and maintenance therapy. The evidence is scattered between the rheumatology and renal literature, where the use of RTX in routine clinical practice is emerging as the norm especially in the United States1.
Objectives To conduct a systematic review of the evidence behind the use of RTX in induction of remission and maintenance in AAV.
Methods The Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE were searched via OvidSP. The American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) were also searched online for relevant abstracts. Free text searches were accompanied with MeSH terms (AAV, rituximab, review, and efficacy) and results subjected to inclusion and exclusion criteria. Exclusions included non-English studies, animal studies, cryoglobulinaemia and secondary vasculitis. Remission was defined by the Birmingham Vasculitis Activity Score (BVAS) and the quality of each study was assessed via the Oxford Centre for Evidence Based Medicine (CEBM) levels of evidence tool.
Results 22 studies met the criteria that studied a total of 729 patients; these included 4 randomised control trials (RCT)2–5, 3 open cohort studies6–8, and 16 case series. Results of the RCTs and open cohort studies are summarised in Table 1. In the case series, 88.2% of the 221 patients achieved either a partial or complete remission following RTX therapy; the mean assessment was carried out at 6.5 months from the start of treatment. Relapses occurred in 19.5% of these patients at an average of 13 months. In RTX maintenance therapy, 92.3% of the 39 patients responded with an averaged follow-up of 12 months. The overall response rate for remission induction included 382 RTX and 109 CYC patients. There was an 81.7% response with RTX vs. 56.9% CYC; mean assessment was carried out at 11 months RTX vs. 8 months CYC. Relapses occurred in 24.9% RTX at 16.5 months vs. 38.5% CYC at 21 months on average. The overall response in maintenance therapy included 170 RTX and 59 CYC patients. There was a 94.7% response with RTX at 21 months vs. 72.9% CYC at 28 months averaged follow-up; 91.6% RTX vs. 51.9% CYC at 34 months averaged follow-up.
Conclusions RTX is non-inferior to CYC in remission induction of AAV patients. RTX is superior to AZA in maintaining remission in newly diagnosed and relapsing AAV patients. RTX treatment allows for a tapered reduction in GCS, as well as showing no differences in adverse events when compared to CYC and AZA. These results support RTX being a safe alternative to those receiving CYC in refractory disease or when contraindicated.
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Disclosure of Interest None declared
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