Continued Inhibition of Structural Damage over 2 Years in Patients with Rheumatoid Arthritis Treated with Rituximab in Combination with Methotrexate

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2010 May 5

PMID 20439295

Citations 19

Authors

Stanley B Cohen

Edward Keystone

Mark C Genovese

Paul Emery

Charles Peterfy

Paul Peter Tak

Matt Cravets

Tim Shaw

David Hagerty

Affiliations

Soon will be listed here.

Abstract

Background: Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors.

Objective: To assess structural damage progression through 2 years.

Methods: Intention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received > or = 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104.

Results: At week 104, significantly lower changes in TSS (1.14 vs 2.81; p<0.0001), erosion score (0.72 vs 1.80; p<0.0001) and joint space narrowing scores (0.42 vs 1.00; p<0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years.

Conclusions: Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitors.

Citing Articles

Therapeutic Utility and Adverse Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs in Inflammatory Arthritis.

Min H, Kim S, Kim H, Lee S Int J Mol Sci. 2022; 23(22).

PMID: 36430392 PMC: 9692587. DOI: 10.3390/ijms232213913.

Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study.

Zeng X, Liu J, Liu X, Wu L, Liu Y, Liao X Arthritis Res Ther. 2022; 24(1):136.

PMID: 35689239 PMC: 9185960. DOI: 10.1186/s13075-022-02821-x.

Pathogenic, glycolytic PD-1+ B cells accumulate in the hypoxic RA joint.

Floudas A, Neto N, Marzaioli V, Murray K, Moran B, Monaghan M JCI Insight. 2020; 5(21).

PMID: 33148884 PMC: 7710281. DOI: 10.1172/jci.insight.139032.

Anti-CD20 monoclonal antibodies: reviewing a revolution.

Casan J, Wong J, Northcott M, Opat S Hum Vaccin Immunother. 2018; 14(12):2820-2841.

PMID: 30096012 PMC: 6343614. DOI: 10.1080/21645515.2018.1508624.

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Guo Q, Wang Y, Xu D, Nossent J, Pavlos N, Xu J Bone Res. 2018; 6:15.

PMID: 29736302 PMC: 5920070. DOI: 10.1038/s41413-018-0016-9.

References

Pincus T, Callahan L . The 'side effects' of rheumatoid arthritis: joint destruction, disability and early mortality. Br J Rheumatol. 1993; 32 Suppl 1:28-37. View

Genovese M, Bathon J, Fleischmann R, Moreland L, Martin R, Whitmore J . Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005; 32(7):1232-42. View

Keystone E, Kavanaugh A, Sharp J, Tannenbaum H, Hua Y, Teoh L . Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized,.... Arthritis Rheum. 2004; 50(5):1400-11. DOI: 10.1002/art.20217. View

Genant H, Jiang Y, Peterfy C, Lu Y, Redei J, Countryman P . Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs. Arthritis Rheum. 1998; 41(9):1583-90. DOI: 10.1002/1529-0131(199809)41:9<1583::AID-ART8>3.0.CO;2-H. View

Strand V, Sharp J . Radiographic data from recent randomized controlled trials in rheumatoid arthritis: what have we learned?. Arthritis Rheum. 2003; 48(1):21-34. DOI: 10.1002/art.10683. View

Genant H, Peterfy C, Westhovens R, Becker J, Aranda R, Vratsanos G . Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2007; 67(8):1084-9. PMC: 2569144. DOI: 10.1136/ard.2007.085084. View

Genant H . Methods of assessing radiographic change in rheumatoid arthritis. Am J Med. 1983; 75(6A):35-47. DOI: 10.1016/0002-9343(83)90473-4. View

Kremer J, Genant H, Moreland L, Russell A, Emery P, Abud-Mendoza C . Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006; 144(12):865-76. DOI: 10.7326/0003-4819-144-12-200606200-00003. View

Pincus T, Callahan L, Sale W, Brooks A, Payne L, Vaughn W . Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum. 1984; 27(8):864-72. DOI: 10.1002/art.1780270805. View

10.

St Clair E, van der Heijde D, Smolen J, Maini R, Bathon J, Emery P . Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004; 50(11):3432-43. DOI: 10.1002/art.20568. View

11.

Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T . Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007; 66(9):1162-7. PMC: 1955155. DOI: 10.1136/ard.2006.068064. View

12.

Breedveld F, Weisman M, Kavanaugh A, Cohen S, Pavelka K, van Vollenhoven R . The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had.... Arthritis Rheum. 2005; 54(1):26-37. DOI: 10.1002/art.21519. View

13.

Cohen S, Emery P, Greenwald M, Dougados M, Furie R, Genovese M . Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006; 54(9):2793-806. DOI: 10.1002/art.22025. View

14.

Klareskog L, van der Heijde D, de Jager J, Gough A, Kalden J, Malaise M . Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004; 363(9410):675-81. DOI: 10.1016/S0140-6736(04)15640-7. View

15.

Keystone E, Emery P, Peterfy C, Tak P, Cohen S, Genovese M . Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2008; 68(2):216-21. DOI: 10.1136/ard.2007.085787. View