Rheumatoid Arthritis: Greenwald M

Keystone E, Emery P, Peterfy CG, Tak PP, Cohen S, Genovese MC, Dougados M, Burmester GR, Greenwald M, Kvien TK, Williams S, Hagerty D, Cravets MW, Shaw T. · Division of Rheumatology, University of Toronto, Toronto, Canada. · Ann Rheum Dis. · Pubmed #18388156 No free full text.

Abstract: OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.

Furst DE, Kolba KS, Fleischmann R, Silverfield J, Greenwald M, Roth S, Hall DB, Roszko PJ, Anonymous00033. · Virginia Mason Research Center Seattle, Washington 98101, USA. · J Rheumatol. · Pubmed #11908554 No free full text.

Abstract: OBJECTIVE: This Phase III, placebo and active controlled, multicenter trial evaluated the efficacy and safety of meloxicam 7.5, 15, and 22.5 mg daily for the treatment of rheumatoid arthritis (RA). METHODS: A 12 week, randomized, double blind, double dummy, parallel group trial compared daily oral meloxicam 7.5, 15, and 22.5 mg to placebo (negative control) and diclofenac 75 mg BID (positive control). A total of 894 patients (18 years of age with confirmed RA who flared following an NSAID-free period) were randomized to be treated. Baseline scores for all endpoints were similar among the treatment groups. Patient assessments were at 0, 2, 4, 8, and 12 weeks or early termination. RESULTS: All treatment groups demonstrated significant improvement from baseline (p < 0.001). Meloxicam 7.5 and 22.5 mg was significantly superior to placebo in all 5 primary efficacy endpoints (swollen joint count, tender joint count, patient pain, patient and physician global; all p < 0.05). Diclofenac 150 mg was superior to placebo for 4 of 5 primary efficacy measures (all but swollen joint count; p < 0.05) and meloxicam 15 mg was superior for 3 of 5 primary endpoints (patient pain and patient and physician global). AUC of patient global, patient pain, and modified Health Assessment Questionnaire demonstrated dose-response (p < 0.04), while AUC ACR20 showed a qualitative trend in the same direction. The rate of gastrointestinal (GI) events during the 12 week trial for all doses of meloxicam and diclofenac did not differ significantly from placebo (23.2-32.0%). GI withdrawals were comparable and not significantly different across all treatment groups (4.3-5.7%). CONCLUSION: This trial demonstrated a dose response relationship for meloxicam 7.5, 15, and 22.5 mg using AUC measurement of response for the treatment of RA. All 3 doses of meloxicam. and positive control, were effective in the treatment of RA. The overall incidence rate of GI events did not differ significantly from placebo in either the meloxicam treatment groups or the positive control.

Mease PJ, Revicki DA, Szechinski J, Greenwald M, Kivitz A, Barile-Fabris L, Kalsi J, Eames J, Leirisalo-Repo M. · Seattle Rheumatology Associates, Seattle, WA 98104, USA. · J Rheumatol. · Pubmed #18050385 No free full text.

Abstract: OBJECTIVE: To evaluate the effect of rituximab treatment on health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA), who have had an inadequate response to disease-modifying antirheumatic drugs, including biologic agents. METHODS: A randomized, multicenter, double-blind, placebo-controlled clinical trial involving 367 rheumatoid factor-positive patients was conducted. Patients received 2 infusions 2 weeks apart of placebo (n = 122), rituximab 500 mg (n = 123), or rituximab 1000 mg (n = 122), with or without glucocorticoids. All patients received stable doses of methotrexate (10 25 mg/wk). Measures included SF-36, assessed at baseline and at 24 weeks, as well as the HAQ and FACIT-Fatigue scale assessed at baseline and monthly for 24 weeks. Patients exceeding prespecified minimal clinically important differences (MCID) were examined. Clinical efficacy measurements (ACR20/50/70 and EULAR responses) were compared with HRQOL outcomes. RESULTS: At 24 weeks, the rituximab 500 mg and 1000 mg groups both reported statistically significantly greater improvements on the SF-36 physical component summary (4.37 and 4.89 points higher, respectively, vs placebo; p < 0.001). SF-36 physical function, bodily pain, vitality, social function, and role-physical subscale scores also statistically significantly improved vs placebo. At 24 weeks, 62.6% and 67.2% of the rituximab 500 mg and 1000 mg groups, respectively, exceeded the MCID of 0.22 in HAQ (p < 0.001). For FACIT-Fatigue, 55.3% and 65.6% of patients exceeded the MCID of 3.5 points compared with 35.2% of placebo over 24 weeks (p < 0.001). ACR20/50/70 and EULAR responders demonstrated greater improvements in mean baseline to 24 week changes in SF-36 and FACIT-Fatigue scores compared with nonresponders (p < 0.05). CONCLUSION: Both rituximab doses in combination with methotrexate were effective in improving all HRQOL outcomes in patients with active RA consistent with clinical efficacy.