Single- versus dual-infusion of B-cell-depleting antibody ocrelizumab in rheumatoid arthritis: results from the Phase III FEATURE trial

Huffstutter, J. Eugene; Taylor, James C.; Schechtman, Joy; Leszczyński, Piotr; Brzosko, Marek; Sedarati, Farhad; Moawad, Dalia; Kapp, Amy V.; Sudlow, Rebecca; Dummer, Wolfgang

doi:10.2217/ijr.11.55

Cited by 5 publications

(9 citation statements)

References 7 publications

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“…OCR500+MTX demonstrated clinical benefit by improving signs and symptoms of RA and radiographic outcomes [10]–[13]; however this dose was associated with an increased incidence of SIEs. OCR200+MTX did not show superior efficacy compared with existing therapies, but was safe and well-tolerated.…”

Section: Discussionmentioning

confidence: 99%

“…The study designs and numbers of patients randomized were reported previously [10]–[13] and are summarized in Table 1. During the DBPC period of STAGE, SCRIPT and FILM, patients received treatment on Days 1 and 15 followed by a retreatment course at Weeks 24 and 26 (patients in FILM were eligible for 2 additional retreatment courses at Weeks 52 and 54, and Weeks 76 and 78).…”

Section: Methodsmentioning

confidence: 99%

“…Patients included in the analyses were participants in 1 of 4 OCR phase III trials [10] – [13] . The analysis population represented a broad spectrum of patients, ranging from patients with early RA who were MTX-naive (FILM [12] , registration no.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro characterization of OCR demonstrated enhanced antibody-dependent cell-mediated cytotoxicity and reduced complement-dependent cytotoxicity compared with rituximab (unpublished data), although the clinical implications of these differences remain unclear. The efficacy and safety of OCR in RA has been evaluated in a robust phase III clinical trial program in a broad spectrum of patients [10] – [13] . In May 2010, OCR development in RA was terminated as a result of the overall risk-benefit assessment from the 2 pivotal phase III studies STAGE and SCRIPT.…”

Section: Introductionmentioning

confidence: 99%

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Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

Emery

Rigby²,

Tak

et al. 2014

PLoS ONE

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ObjectiveThe objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA).MethodsThis 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.ResultsOverall, 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.ConclusionsIn 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 RegistrationSTAGE Clinical Trials.gov NCT00406419 SCRIPT Clinical Trials.gov NCT00476996 FILM Clinical Trials.gov NCT00485589 FEATURE Clinical Trials.gov NCT00673920

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

Emery

Rigby²,

Tak

et al. 2014

PLoS ONE

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“…The use of intravenous (IV) ocrelizumab for the treatment of RA was studied in four phase III, international, randomized, double-blind, placebo-controlled trials: SCRIPT, STAGE, FILM, and FEATURE. STAGE [ 9 ], FILM [ 10 ], and FEATURE [ 11 ] studied ocrelizumab in RA patients on stable MTX who had inadequate responses to MTX, while SCRIPT [ 12 ] studied ocrelizumab in RA patients taking MTX or leflunomide who had inadequate responses to at least one TNF antagonist. Patients in the STAGE, FILM, and SCRIPT studies continued taking their stable doses of MTX or leflunomide and were assigned to receive ocrelizumab at 200 mg × 2, 500 mg × 2, or placebo × 2 at baseline and at week 24.…”

Section: Anti-cd20 Mabs In Rheumatoid Arthritismentioning

confidence: 99%

Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment

Mills

Mao-Draayer

2017

Autoimmun Highlights

156

119

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The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine–human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab. We conducted a literature search of relevant randomized clinical trials in the PubMed database and ongoing trials in Clinicaltrials.gov. Most of these trials have evaluated intravenous ocrelizumab or subcutaneous ofatumumab in rheumatoid arthritis, multiple sclerosis, or systemic lupus erythematosus. Understanding how newer anti-CD20 mAbs compare with rituximab in terms of efficacy, safety, convenience, and cost is important for guiding future management of anti-CD20 mAb therapy in autoimmune diseases.

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Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis

Abushouk

Ahmed

Ismail³

et al. 2017

Rheumatol Int

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We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.

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Single- versus dual-infusion of B-cell-depleting antibody ocrelizumab in rheumatoid arthritis: results from the Phase III FEATURE trial

Cited by 5 publications

References 7 publications

Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment

Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis

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