Rachael McCool1, Katy Wilson1, Mick Arber1, Kelly Fleetwood2, Sydney Toupin2, Howard Thom3, Iain Bennett4, Susan Edwards5. 1. York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York YO10 5NQ, UK. 2. Quantics Biostatistics, West End House, 28 Drumsheugh Gardens, Edinburgh EH3 7RN, UK. 3. Bristol Medical School: Population Health Sciences, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK. 4. Health Economics and Evidence Synthesis, Global Access Center of Excellence, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, CH-4070, Switzerland. 5. Health Economics and Evidence Synthesis, Global Access Center of Excellence, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, CH-4070, Switzerland. Electronic address: susan.edwards.se1@roche.com.
Abstract
BACKGROUND: Ocrelizumab was approved for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) by the US Food and Drug Administration in March 2017 and by the European Medicines Agency in January 2018. These approvals were based on two pivotal randomized controlled trials (RCTs), OPERA I and OPERA II, comparing ocrelizumab 600 mg with an active comparator, interferon β-1a 44 μg (Rebif), and the first trial with positive results in patients with PPMS, which compared ocrelizumab with placebo. However, direct evidence of the efficacy and safety of ocrelizumab in RMS compared with other disease-modifying therapies (DMTs) approved for RMS is not available from RCTs. In the absence of such RCTs, network meta-analyses (NMAs) were conducted to compare indirectly the relative efficacy and safety of ocrelizumab with all other approved DMTs for the treatment of RMS. METHODS: Systematic literature searches were conducted in MEDLINE, Embase, the Cochrane Library, trial registers, relevant conference websites and health technology assessment agency websites. Eligible RCTs evaluated approved treatments for multiple sclerosis (MS) in which more than 75% of patients had a relapsing form of MS. NMAs were conducted for four efficacy and three safety outcomes, and treatment hierarchies were generated for each outcome using surface under the cumulative ranking curve (SUCRA) values. RESULTS: Results suggest that ocrelizumab has superior efficacy to 10 of the 17 treatments in the 12-week confirmed disability progression network and 12 of the 17 treatments in the annualized relapse rate network (both including placebo). The efficacy of ocrelizumab was comparable with the other treatments in both networks. In the serious adverse events and discontinuation due to adverse events networks, ocrelizumab demonstrated a safety profile comparable with all other treatments (including placebo). SUCRA values consistently ranked ocrelizumab among the most effective or tolerable treatments across all outcomes. CONCLUSIONS: Results suggest that ocrelizumab has an efficacy superior to or comparable with all other currently approved DMTs across all endpoints analyzed, and a similar safety profile, indicating it offers a valuable package for the treatment of patients with RMS.
BACKGROUND:Ocrelizumab was approved for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) by the US Food and Drug Administration in March 2017 and by the European Medicines Agency in January 2018. These approvals were based on two pivotal randomized controlled trials (RCTs), OPERA I and OPERA II, comparing ocrelizumab 600 mg with an active comparator, interferon β-1a 44 μg (Rebif), and the first trial with positive results in patients with PPMS, which compared ocrelizumab with placebo. However, direct evidence of the efficacy and safety of ocrelizumab in RMS compared with other disease-modifying therapies (DMTs) approved for RMS is not available from RCTs. In the absence of such RCTs, network meta-analyses (NMAs) were conducted to compare indirectly the relative efficacy and safety of ocrelizumab with all other approved DMTs for the treatment of RMS. METHODS: Systematic literature searches were conducted in MEDLINE, Embase, the Cochrane Library, trial registers, relevant conference websites and health technology assessment agency websites. Eligible RCTs evaluated approved treatments for multiple sclerosis (MS) in which more than 75% of patients had a relapsing form of MS. NMAs were conducted for four efficacy and three safety outcomes, and treatment hierarchies were generated for each outcome using surface under the cumulative ranking curve (SUCRA) values. RESULTS: Results suggest that ocrelizumab has superior efficacy to 10 of the 17 treatments in the 12-week confirmed disability progression network and 12 of the 17 treatments in the annualized relapse rate network (both including placebo). The efficacy of ocrelizumab was comparable with the other treatments in both networks. In the serious adverse events and discontinuation due to adverse events networks, ocrelizumab demonstrated a safety profile comparable with all other treatments (including placebo). SUCRA values consistently ranked ocrelizumab among the most effective or tolerable treatments across all outcomes. CONCLUSIONS: Results suggest that ocrelizumab has an efficacy superior to or comparable with all other currently approved DMTs across all endpoints analyzed, and a similar safety profile, indicating it offers a valuable package for the treatment of patients with RMS.
Authors: Caitlin H Daly; Lawrence Mbuagbaw; Lehana Thabane; Sharon E Straus; Jemila S Hamid Journal: BMC Med Res Methodol Date: 2020-10-28 Impact factor: 4.615