Regulation-Driven Variation in Utilization and Cost of B-Cell Depleting Therapies for Multiple Sclerosis: A Cross-National Study

Background: Rituximab and ocrelizumab target the same CD20 receptor. Rituximab is off-patent and prescribed off-label; ocrelizumab is licensed and patent-protected. Whether the resulting differences in utilization and cost reflect clinical value or regulatory structure has not been examined. Objective: To determine whether utilization and cost of B-cell depleting therapy across six health systems track regulatory approval status more closely than comparative effectiveness. Methods: We examined rituximab and ocrelizumab utilization and cost in Sweden, France, Germany, the United Kingdom, Italy and the United States (2016-2024). Costs were drawn from published national sources on a consistent ex-factory basis. Utilization was registry-measured for Sweden, France and Germany, measured from national claims for the United States, and estimated from indirect data for the United Kingdom and Italy. Weighted annual costs per patient on B-cell depleting therapy were modeled by Monte Carlo simulation (10,000 iterations). Results: Rituximab constituted the near-totality of B-cell depleting therapy in Sweden but 2.3% to 18.7% of use in the other five systems. Mean annual cost per patient ranged from $3,014 (Sweden) to $52,506 (United States), a 17-fold difference, with the four other European systems between $18,140 and $26,262. Adopting Sweden's utilization pattern was associated with modeled five-year per-patient differences in drug acquisition cost of $76,000 to $248,000. Conclusion: Utilization and cost align more closely with regulatory approval status than with available effectiveness data. International reference pricing acts on the price of the licensed agent but leaves intact the regulatory asymmetry that determines which agent is prescribed.