Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.
<h4>Objective</h4>The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).<h4>Methods</h4>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, ST...
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oai:doaj.org-article:49652c7e07ca420993dde7e84ab236dd2021-11-18T08:34:17ZSafety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.1932-620310.1371/journal.pone.0087379https://doaj.org/article/49652c7e07ca420993dde7e84ab236dd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498318/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920.Paul EmeryWilliam RigbyPaul P TakThomas DörnerEwa OlechCarmen MartinLaurie MillarHelen TraversElena FishelevaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87379 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Paul Emery William Rigby Paul P Tak Thomas Dörner Ewa Olech Carmen Martin Laurie Millar Helen Travers Elena Fisheleva Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| description |
<h4>Objective</h4>The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920. |
| format |
article |
| author |
Paul Emery William Rigby Paul P Tak Thomas Dörner Ewa Olech Carmen Martin Laurie Millar Helen Travers Elena Fisheleva |
| author_facet |
Paul Emery William Rigby Paul P Tak Thomas Dörner Ewa Olech Carmen Martin Laurie Millar Helen Travers Elena Fisheleva |
| author_sort |
Paul Emery |
| title |
Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| title_short |
Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| title_full |
Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| title_fullStr |
Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| title_full_unstemmed |
Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. |
| title_sort |
safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase iii program. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/49652c7e07ca420993dde7e84ab236dd |
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