| Summary: | The CADTH reanalysis, which based annualized relapse rates (ARRs) on multiple sclerosis (MS) disease duration rather than Expanded Disability Status Scale (EDSS) scores, applied a treatment-waning effect; considered all first, second, and third lines of therapies; removed EDSS improvement; and based effect estimates on predefined confirmed disease progression (CDP) definitions, found that ofatumumab was not cost-effective as a first-line therapy. The analysis found that ofatumumab was extendedly dominated by ocrelizumab and glatiramer acetate; that is, more QALYs would be generated at lower costs by a mix of ocrelizumab and glatiramer use. When considering ofatumumab as a second- or third-line therapy, it was not cost-effective as it produced fewer QALYs at a high cost, and was therefore dominated by alemtuzumab and cladribine. These findings were driven largely by a sponsor-submitted network meta-analysis (NMA) that showed wide confidence intervals concerning the relative efficacy of ofatumumab versus other disease-modifying therapies (DMTs). Although point estimates showed ofatumumab was inferior or superior to some DMTs, these conclusions were highly uncertain. At minimum, ofatumumab should be priced no higher than the lowest-cost DMT with similar efficacy. Where it was found that ofatumumab was not as clinically effective as other DMTs, a price reduction of 45.2% would be required to ensure cost-effectiveness at a threshold of $50,000 per QALY when considering only first-line therapies. If second- and third-line therapies are considered relevant comparators, a 45.4% price reduction would be required
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