Advertisement

Clinical Rheumatology

, Volume 34, Issue 10, pp 1801–1805 | Cite as

Updated systematic review and meta-analysis of randomized controlled trials comparing low- versus high-dose rituximab for rheumatoid arthritis

  • Markus Bredemeier
  • Guilherme G. Campos
  • Fernando K. de Oliveira
Brief Report

Abstract

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.

Keywords

Arthritis rheumatoid Dose-response relationship drug Meta-analysis Review systematic Rituximab 

Notes

Acknowledgments

We thank Mabel Fernandes Figueiró and Drs. Airton Tetelbom Stein and Sérgio Antônio Sirena on their valuable support.

Disclosures

None.

Supplementary material

10067_2015_2977_MOESM1_ESM.doc (13.4 mb)
ESM 1 (DOC 13725 kb)

References

  1. 1.
    Bredemeier M, de Oliveira FK, Rocha CM (2014) Low- versus high-dose rituximab for rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 66:228–35. doi: 10.1002/acr.22116 CrossRefGoogle Scholar
  2. 2.
    Vital EM, Md Yusof MY, Emery P (2014) Choosing the right rituximab dose for the right patient: comment on the article by Bredemeier et al. Arthritis Care Res (Hoboken) 66:1591–3. doi: 10.1002/acr.22379 CrossRefGoogle Scholar
  3. 3.
    Bredemeier M (2014) Reply. Arthritis Care Res (Hoboken) 66:1593–6. doi: 10.1002/acr.22382 CrossRefGoogle Scholar
  4. 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. 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. 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
  7. 7.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. doi: 10.1136/bmj.b2535 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–24CrossRefPubMedGoogle Scholar
  9. 9.
    Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C et al (1995) American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38:727–35CrossRefPubMedGoogle Scholar
  10. 10.
    Batticciotto A, Varisco V, Antivalle M, Talotta R, Rigamonti F, Ventura D et al (2013) Dose reduction in patients with rheumatoid arthritis responding to the standard rituximab regimen. Ann Rheum Dis 72(Suppl):877CrossRefGoogle Scholar
  11. 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. 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. 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. 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
  15. 15.
    Bredemeier M (2012) Last observation carried forward approach threatens the validity of intent-to-treat analysis in fibromyalgia trials: comment on the article by Arnold et al. Arthritis Rheum 64:2809–10. doi: 10.1002/art.34493 CrossRefPubMedGoogle Scholar
  16. 16.
    Leandro MJ, Becerra-Fernandez E (2011) B-cell therapies in established rheumatoid arthritis. Best Pract Res Clin Rheumatol 25:535–48. doi: 10.1016/j.berh.2011.10.005 CrossRefPubMedGoogle Scholar
  17. 17.
    Lydersen S (2015) Statistical review: frequently given comments. Ann Rheum Dis 74:323–5. doi: 10.1136/annrheumdis-2014-206186
  18. 18.
    Ma Y, Mazumdar M, Memtsoudis SG (2012) Beyond repeated-measures analysis of variance: advanced statistical methods for the analysis of longitudinal data in anesthesia research. Reg Anesth Pain Méd 37:99–105. doi: 10.1097/AAP.0b013e31823ebc74 PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2015

Authors and Affiliations

  • Markus Bredemeier
    • 1
  • Guilherme G. Campos
    • 1
  • Fernando K. de Oliveira
    • 1
  1. 1.Rheumatology ServiceHospital Nossa Senhora da Conceição − Grupo Hospitalar ConceiçãoPorto AlegreBrazil

Personalised recommendations