Tags

Type your tag names separated by a space and hit enter

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 Sep; 54(9):2793-806.AR

Abstract

OBJECTIVE

To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population.

METHODS

We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks.

RESULTS

Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab-treated patients, who also had clinically meaningful improvements in fatigue, disability, and health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity. The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group.

CONCLUSION

At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.

Authors+Show Affiliations

Radiant Research, Dallas, Texas 75235, USA. stanleycohen@radiantresearch.comNo 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 availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16947627

Citation

Cohen, Stanley B., et al. "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 and Rheumatism, vol. 54, no. 9, 2006, pp. 2793-806.
Cohen SB, Emery P, Greenwald MW, et al. 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.
Cohen, S. B., Emery, P., Greenwald, M. W., Dougados, M., Furie, R. A., Genovese, M. C., Keystone, E. C., Loveless, J. E., Burmester, G. R., Cravets, M. W., Hessey, E. W., Shaw, T., & Totoritis, M. C. (2006). 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 and Rheumatism, 54(9), 2793-806.
Cohen SB, et al. 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. PubMed PMID: 16947627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Cohen,Stanley B, AU - Emery,Paul, AU - Greenwald,Maria W, AU - Dougados,Maxime, AU - Furie,Richard A, AU - Genovese,Mark C, AU - Keystone,Edward C, AU - Loveless,James E, AU - Burmester,Gerd-Rüdiger, AU - Cravets,Matthew W, AU - Hessey,Eva W, AU - Shaw,Timothy, AU - Totoritis,Mark C, AU - ,, PY - 2006/9/2/pubmed PY - 2006/11/10/medline PY - 2006/9/2/entrez SP - 2793 EP - 806 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 54 IS - 9 N2 - OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab-treated patients, who also had clinically meaningful improvements in fatigue, disability, and health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity. The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group. CONCLUSION: At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16947627/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_ L2 - https://doi.org/10.1002/art.22025 DB - PRIME DP - Unbound Medicine ER -