The objective of a study was to determine the safety of Ocrelizumab in patients with rheumatoid arthritis.
An analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 Ocrelizumab phase III trials in rheumatoid arthritis ( SCRIPT, STAGE, FILM and FEATURE ) was performed.
Overall, 868 patients received placebo, 1064 patients Ocrelizumab 200 mg×2 ( or 400 mg×1 ) ( OCR200 ), and 827 patients Ocrelizumab 500 mg×2 ( OCR500 ) plus background Methotrexate 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 Ocrelizumab plus Methotrexate and placebo plus Methotrexate groups.
Infusion-related reactions were more common with Ocrelizumab plus Methotrexate and decreased in frequency with subsequent infusions.
Serious infusion-related reactions were rare ( 0.1% ). Serious infections occurred more frequently with Ocrelizumab plus Methotrexate.
In the meta-analysis, a statistically significant difference from placebo plus Methotrexate in incidence of serious infectious events per 100 patient-years of 2.4 ( 95% CI, 0.3-4.5 ) was observed with Ocrelizumab plus Methotrexate, but not with OCR200 plus Methotrexate ( 0.6; 95% CI, -1.3 to 2.4 ).
Patients recruited in Asia exhibited a higher risk of serious infections ( hazard ratio, HR=1.78; 95% CI, 1.03-3.06 ).
The incidence of human anti-human antibodies was less than 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 Ocrelizumab dose groups.
In conclusion, in placebo-controlled clinical trials of rheumatoid arthritis, OCR500 plus Methotrexate was associated with a higher risk of serious infections compared with placebo plus Methotrexate.
The safety profile of OCR200 plus Methotrexate was comparable with placebo plus Methotrexate. ( Xagena )
Emery P et al, PLoS One 2014;9:e87379