Abstract | OBJECTIVE: METHODS: This was an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE). Safety data per study and the results of a meta-analysis of serious infectious events (SIEs) are presented. RESULTS: Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1) (OCR200), and 827 patients OCR 500 mg×2 (OCR500) plus background methotrexate (MTX) at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse events and serious adverse events was comparable between the OCR+MTX and placebo +MTX groups. Infusion-related reactions were more common with OCR+MTX and decreased in frequency with subsequent infusions. Serious infusion-related reactions were rare (0.1%). Serious infections occurred more frequently with OCR500+MTX. In the meta-analysis, a statistically significant difference from placebo +MTX in incidence of SIEs per 100 patient-years of 2.4 (95% CI, 0.3-4.5) was observed with OCR500+MTX, but not with OCR200+MTX (0.6; 95% CI, -1.3 to 2.4). Patients recruited in Asia exhibited a higher risk of serious infections (hazard ratio, 1.78; 95% CI, 1.03-3.06). The incidence of human anti-human antibodies was <5%. Long-term follow-up indicated no differences in malignancy rates between the treatment groups. There was no apparent difference in time to B-cell repletion between the OCR dose groups. CONCLUSIONS: In placebo-controlled clinical trials of RA, OCR500+MTX was associated with a higher risk of serious infections compared with placebo +MTX. The safety profile of OCR 200+MTX was comparable with placebo+MTX. TRIAL REGISTRATION: STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920.
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Authors | Paul Emery, William Rigby, Paul P Tak, Thomas Dörner, Ewa Olech, Carmen Martin, Laurie Millar, Helen Travers, Elena Fisheleva |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 2
Pg. e87379
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24498318
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Antirheumatic Agents
- ocrelizumab
- Methotrexate
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Topics |
- Antibodies, Monoclonal, Humanized
(adverse effects, therapeutic use)
- Antirheumatic Agents
(adverse effects, therapeutic use)
- Arthritis, Rheumatoid
(drug therapy)
- Clinical Trials, Phase III as Topic
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Humans
- Infections
(chemically induced)
- Male
- Meta-Analysis as Topic
- Methotrexate
(adverse effects, therapeutic use)
- Middle Aged
- Multicenter Studies as Topic
- Neoplasms
(chemically induced)
- Randomized Controlled Trials as Topic
- Treatment Outcome
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