Waking up to darkness
Authors: A. C. Lowney, S. A. Ryan, A. Ryan, S. Harney
Journal: BMJ (2011)

<h3>Background</h3> Cyclophosphamide (CYC) is currently used to induce remission in patients with ANCA-associated vasculitis (AAV). Once remission induction is successful Azathioprine (AZA) is given as maintenance (1). Concerns surround the use of cyclophosphamide which has an undesirable safety profile, limiting its use in patients. AZA has shown to be effective at maintenance, however rates of relapse on AZA are high. Rituximab (RTX) is a biologic with a high specificity to B cells. Its mechanism of action (B cell apoptosis) may mean that it can be used for both the induction and maintenance of remission, with a superior long-term safety profile. <h3>Objectives</h3> To conduct a systematic review of literature to determine the efficacy of rituximab as a remission inducing and maintaining agent. <h3>Methods</h3> A systematic review of literature was conducted by searching PubMed and Cochrane library with the search phrase “rituximab AND ANCA-associated vasculitis”. The following criteria was then applied: randomised controlled trial (RCT) in the English language. Only original papers were accepted if it pertained to RTX for either induction or maintenance of remission. <h3>Results</h3> 1008 papers were initially identified and after the search strategy was applied 9 RCTs were analysed. The RAVE trial compared RTX to CYC in 197 patients with AAV in a double-blind double-dummy trial. The result of the RAVE trial indicated that RTX was as effective as CYC at maintaining remission. The RITUXVAS trial, which was partially blinded and had a sample of 44 patients also came to the same conclusion. Both the RAVE and RITUXVAS trials also showed that an initial dose of RTX was as effective as continuous immunosuppression over the trial length. Further RCTs were published from the RAVE and RITUXVAS studies including a follow up of patients from the RITUXVAS trial at 24 months which showed no increased rates of relapse or adverse events between the groups. The RAVE study also showed that RTX was effective to be used on multiple occasions to induce remission irrespective of the initial remission inducing agent. The MAINRITSAN1 study was a non-blinded randomised trial which compared RTX with azathioprine for maintenance in 115 patients with AAV. The results of this trial showed that RTX was superior than AZA at maintenance with only 5% on RTX compared with 29% on AZA relapsing. The long-term follow up of patients in the trial, showed that at 60 months, patients who received RTX were less likely to have relapsed. The MAINRITSAN2 trial indicated that there was no difference between a fixed vs tailored RTX dose, meaning that a lower tailored dose was as effective as a higher fixed dose. The MAINRITSAN 3 paper was a double-blind trial that indicated that biannual RTX for maintenance was superior than placebo at maintaining remission. <h3>Conclusion</h3> RTX is as effective as CYC at inducing remission, with both the RAVE and RITUXVAS trials sharing similar conclusions. Currently the research indicates that an initial dose of RTX can maintain remission at similar rates as continuous AZA, however its superiority is yet to be determined. The MAINRITSAN 1 trial was unblinded in its protocol with the data indicating it drastically overestimated the efficacy of both RTX and AZA. Therefore, more research is needed to validate the claim that RTX is superior than AZA at maintenance. <h3>References</h3> [1]Yates, M, et al. 2016. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Annals of the Rheumatic Diseases 75, 1583–1594. doi:10.1136/annrheumdis-2016-209133 <h3>Acknowledgements</h3> I would like to thank Dr Marwan Bukhari for his continued support and feedback during this project. <h3>Disclosure of Interests</h3> None declared