CADTH undertook reanalyses of the sponsor’s economic models for satralizumab administered as monotherapy and in combination with immunosuppressive therapies (IST) to address some of the identified limitations. In both models, CADTH’s base-case reanalysis included a definition of relapse that is more reflective of clinical practice and removed caregiver disutilities. In addition, in the economic model for satralizumab plus IST compared with IST alone, CADTH further assumed no differences in the frequency of adverse events between groups. CADTH’s findings remained aligned with the sponsor, such that satralizumab is not cost-effective at a $50,000 per quality-adjusted life-year (QALY) willingness-to-pay (WTP) threshold as monotherapy or in combination with IST. The incremental cost-effectiveness ratio (ICER) for satralizumab monotherapy versus no treatment was $337,535 per QALY gained, and the ICER for satralizumab plus IST versus IST alone was $752,179 per QALY gained. Price-reduction analyses suggest that, for satralizumab to achieve an ICER below $50,000 per QALY gained, reductions in the price by 80% when administered as monotherapy, and 89% when administered in combination with IST, would be required. Relapse was incorporated into the model as the main treatment-effectiveness measure to define progression and movement within the sponsor’s economic model. As such, the model results were primarily driven by the definition of relapse. The incremental benefit ofsatralizumab as monotherapy or as an add-on therapy to IST was minimal over the trial’s observed period, while the majority (approximately 98%) of the incremental benefits were achieved over the remainder of the extrapolated time horizon under the assumption of persistent treatment effects over time. CADTH was further unable to address the inherent limitations with the conceptualization of the economic model and the uncertainties resulting from the overestimation of life-years. Given the lack of comparative clinical information, the cost-effectiveness of satralizumab compared with IST, and compared with eculizumab, is unknown.