Background Since the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. The recommendation in fact sheet is the administration of two infusions of 1 g in each cycle but some studies have used two infusions of 500 mg. Currently the most suitable pattern for its use is not established.
Objectives To systematically review the published evidence to date regarding on the difference in efficacy in the treatment of RA with RTX when used at a dose of 2 x 500 mg (1 g) or 2 x 1000 mg (2 g) per cycle.
Methods A sensitive search of all published studies on the difference in the efficacy of RTX in RA patients used at a dose of 1 and 2 g per cycle was performed in Medline, Embase and Cochrane Central databases since its inception until July 2013. We selected all studies involving adult patients with RA treated with RTX in which intervention was described as treatment with RTX at a dose of 1 g per cycle and comparator as the administration of RTX at a dose of 2 g per cycle. Any standardized measure of efficacy in RA was considered as outcome measure at two years of follow-up. Although meta analysis, systematic reviews, clinical trials and cohorts well designed were preferably selected, finally we also included open studies and all studies that showed a methodologically correct subanalysis related to the question even if it had not been his main objective. After removing duplicates, an initial selection by reading titles, a second selection after reading abstracts and, finally, full reading of selected studies, assessing the methodological quality by levels of the Oxford Centre for Evidence Based Medicine Evidence (2001 update) where applicable, was carried out. A manual search of the references of included studies was also performed.
Results A total of 451 citations about the treatment of RA patients with RTX used at a dose of 1 and 2 g per cycle were identified, which were reduced to 46 after removing duplicates and selection by reading titles and abstracts. Of the 46 articles selected, finally 14 were included in the review, 3 reviews, 2 of them systematic and one not systematic, 5 corresponding to 4 clinical trials, 3 open studies and 3 abstracts, two of them about the same retrospective cohort and, the third one, an open study previously included as a publication. Although published outside the period included in this review, an article about a systematic review and meta-analysis was included because it provides valuable information for the same.
Conclusions RTX shows an equivalent overall clinical efficacy administered at doses of 1 and 2 g per cycle in the treatment of RA patients (level of evidence 1a, grade of recommendation A). However, there may be differences in extreme efficacy parameters with trend, not statistically significant, to a more ACR70 response or EULAR good response at the dose of 2 g per cycle.
Acknowledgements This work has been funded by the Spanish Society of Rheumatology.
Disclosure of Interest A. M. Ortiz Grant/research support: Spanish Society of Rheumatology, M. Rosario Lozano: None declared, C. Martínez Fernández: None declared, I. González-Άlvaro Grant/research support: Spanish Society of Rheumatology