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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. 2006 May; 54(5):1390-400.AR

Abstract

OBJECTIVE

To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents.

METHODS

A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted.

RESULTS

Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo.

CONCLUSION

Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.

Authors+Show Affiliations

Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Leeds, UK. p.emery@leeds.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16649186

Citation

Emery, Paul, et al. "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 and Rheumatism, vol. 54, no. 5, 2006, pp. 1390-400.
Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. 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. 2006;54(5):1390-400.
Emery, P., Fleischmann, R., Filipowicz-Sosnowska, A., Schechtman, J., Szczepanski, L., Kavanaugh, A., Racewicz, A. J., van Vollenhoven, R. F., Li, N. F., Agarwal, S., Hessey, E. W., & Shaw, T. M. (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 and Rheumatism, 54(5), 1390-400.
Emery P, et al. 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. 2006;54(5):1390-400. PubMed PMID: 16649186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Emery,Paul, AU - Fleischmann,Roy, AU - Filipowicz-Sosnowska,Anna, AU - Schechtman,Joy, AU - Szczepanski,Leszek, AU - Kavanaugh,Arthur, AU - Racewicz,Artur J, AU - van Vollenhoven,Ronald F, AU - Li,Nicole F, AU - Agarwal,Sunil, AU - Hessey,Eva W, AU - Shaw,Timothy M, AU - ,, PY - 2006/5/2/pubmed PY - 2006/8/5/medline PY - 2006/5/2/entrez SP - 1390 EP - 400 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 54 IS - 5 N2 - OBJECTIVE: To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents. METHODS: A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted. RESULTS: Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo. CONCLUSION: Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16649186/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_ L2 - https://doi.org/10.1002/art.21778 DB - PRIME DP - Unbound Medicine ER -