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.

Précis

Rituximab’s share of anti-CD20 use in multiple sclerosis, and its cost, track national off-label reimbursement rules rather than comparative effectiveness, across six high-income health systems.

Highlights

What is already known. Rituximab and ocrelizumab deplete the same B-cell population, and a phase 3 randomized trial has now reported rituximab non-inferior to ocrelizumab on the primary radiological endpoint. Rituximab is off-patent and prescribed off-label; ocrelizumab is licensed and patent-protected. Whether the large international differences in which agent is used, and at what cost, reflect clinical value or regulatory structure had not been examined.

What this study adds. Across Sweden, France, Germany, the United Kingdom, Italy and the United States, rituximab’s share of anti-CD20 use ranged from 96% to 2.3% and mean annual cost per treated patient from $3,014 to $52,506. Because United States and Swedish ex-factory prices differ by the same 2.80-fold for both drugs, the cost gap separates exactly into a price component and a utilization component.

What it means for decision making. Utilization tracked national off-label reimbursement rules rather than comparative effectiveness or price. Adopting Sweden’s utilization pattern corresponds to modeled five-year drug-acquisition differences of $76,000 to $248,000 per patient. International reference pricing acts on the price of the licensed agent and leaves the regulatory asymmetry intact, so measures that change which agent may be reimbursed, such as treatment compendia and off-label outcome tracking, are the operative levers.