Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial.

Details

Serval ID
serval:BIB_B8BE85797CFA
Type
Article: article from journal or magazin.
Collection
Publications
Title
Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial.
Journal
Annals of the Rheumatic Diseases
Author(s)
Stohl W., Gomez-Reino J., Olech E., Dudler J., Fleischmann R.M., Zerbini C.A., Ashrafzadeh A., Grzeschik S., Bieraugel R., Green J., Francom S., Dummer W.
ISSN
1468-2060 (Electronic)
ISSN-L
0003-4967
Publication state
Published
Issued date
2012
Volume
71
Number
8
Pages
1289-1296
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. PDF type: Extended report
Abstract
OBJECTIVE: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients.
METHODS: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (ΔmTSS) at week 104). Analyses are reported for week 52 outcomes.
RESULTS: At week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in ΔmTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)).
CONCLUSIONS: OCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections.
Keywords
Antibodies, Monoclonal, Humanized/adverse effects, Antibodies, Monoclonal, Humanized/therapeutic use, Antirheumatic Agents/adverse effects, Antirheumatic Agents/therapeutic use, Arthritis, Rheumatoid/drug therapy, Arthritis, Rheumatoid/pathology, Disease Progression, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Immunocompromised Host, Infection/epidemiology, Infection/etiology, Infusions, Intravenous, Joints/drug effects, Joints/pathology, Male, Methotrexate/adverse effects, Methotrexate/therapeutic use, Middle Aged, Severity of Illness Index, Treatment Outcome
Pubmed
Web of science
Open Access
Yes
Create date
26/04/2013 9:28
Last modification date
20/08/2019 15:26
Usage data