Updated systematic review and meta-analysis of randomized controlled trials comparing low- versus high-dose rituximab for rheumatoid arthritis
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The purpose of this study is to update a systematic review and meta-analysis comparing low- (2 × 500 or 1 × 1000 mg) and high-dose (2 × 1000 mg) rituximab (RTX) for the treatment of rheumatoid arthritis (RA), considering the recent emergence of new evidence. The systematic literature review searching for randomized controlled trials (RCTs) was updated to November 6, 2014 using the PubMed, EMBASE, Cochrane Library, Web of Science databases, and hand searching. The primary outcomes were the American College of Rheumatology (ACR) criteria for 20 % improvement (ACR20), ACR50, and ACR70 responses and the Disease Activity Score in 28 joints (DAS28) at 24 and 48/52 weeks. The secondary outcomes were change in Health Assessment Questionnaire (HAQ) score, change in the radiographic modified Total Sharp Score (mTSS), levels of immunoglobulin G (IgG), and adverse events. In total, seven RCTs were identified, including two new full publication versions and one abstract of RCTs. There were no significant differences in the primary outcomes and change in HAQ, although the mean change in mTSS was 0.25 units (95 % CI, 0.01 to 0.49; P = 0.04) higher in low-dose group at week 52. Two RCTs did not demonstrate difference between the RTX regimens for maintaining clinical response (obtained initially using high-dose RTX) in anti-TNF-experienced patients. IgG levels were significantly higher (P ≤ 0.02), and first infusion reactions were less frequent in the low-dose group (P = 0.02). Our updated results further support the similar efficacy of both RTX regimens in different subsets of RA patients, demonstrating a better clinical and laboratory safety profile of the low-dose scheme.
KeywordsArthritis rheumatoid Dose-response relationship drug Meta-analysis Review systematic Rituximab
We thank Mabel Fernandes Figueiró and Drs. Airton Tetelbom Stein and Sérgio Antônio Sirena on their valuable support.
- 4.Leandro MJ (2015) Rituximab and other B cell targeted therapies for rheumatoid arthritis. In: Romain PL, Maini RN (Eds), Uptodate, Waltham, MA. http://www.uptodate.com/contents/rituximab-and-other-b-cell-targeted-therapies-for-rheumatoid-arthritis. Accessed on 12 January 2015
- 5.Peterfy C, Emery P, Tak PP, Østergaard M, DiCarlo J, Otsa K et al (2014) MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study. Ann Rheum Dis. doi: 10.1136/annrheumdis-2014-206015 Google Scholar
- 6.Mariette X, Rouanet S, Sibilia J, Combe B, Le Loet X, Tebib J et al (2014) Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial. Ann Rheum Dis 73:1508–14. doi: 10.1136/annrheumdis-2013-203480 CrossRefPubMedGoogle Scholar
- 11.Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, for the DANCER Study Group et al (2006) The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIb randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54:1390–1400CrossRefPubMedGoogle Scholar
- 12.Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ et al (2010) Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis 69:1629–35. doi: 10.1136/ard.2009.119933 PubMedCentralCrossRefPubMedGoogle Scholar
- 13.Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W et al (2012) Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis 71:351–7. doi: 10.1136/annrheumdis-2011-200170 PubMedCentralCrossRefPubMedGoogle Scholar
- 14.Rubbert-Roth A, Tak PP, Zerbini C, Tremblay JL, Carreno L, Armstrong G et al (2010) Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR). Rheumatology (Oxford) 49:1683–93. doi: 10.1093/rheumatology/keq116 CrossRefGoogle Scholar
- 17.Lydersen S (2015) Statistical review: frequently given comments. Ann Rheum Dis 74:323–5. doi: 10.1136/annrheumdis-2014-206186