Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.
OBJECTIVE
The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).


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.


BACKGROUND
STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom ; NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
Paul
P
Emery
The Geisel School of Medicine at Darthmouth, Lebanon, New Hampshire, United States of America.
William
W
Rigby
Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Paul P
PP
Tak
Charité University Hospitals and DRFZ, Berlin, Germany.
Thomas
T
Dörner
University of Nevada School of Medicine, Las Vegas, Nevada, United States of America.
Ewa
E
Olech
Roche Products, Ltd, Welwyn Garden City, United Kingdom.
Carmen
C
Martin
Roche Products, Ltd, Welwyn Garden City, United Kingdom.
Laurie
L
Millar
Roche Products, Ltd, Welwyn Garden City, United Kingdom.
Helen
H
Travers
Roche Products, Ltd, Welwyn Garden City, United Kingdom.
Elena
E
Fisheleva
D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007239:Infections / Q000139:chemically induced; D008297:Male; D015201:Meta-Analysis as Topic; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C533411:ocrelizumab; D008727:Methotrexate