Recommendations for the use of off-label rituximab for the treatment of multiple sclerosis in low-resource settings

Background: Rituximab is a commonly used off-label disease-modifying treatment (DMT) for multiple sclerosis (MS). The MS International Federation (MSIF) articulated the need for evidence-based recommendations on the use of the medicine in 2021, with an assessment focused on low-resource settings where licensed alternatives may not be accessible. Objective: To provide recommendations intended to support people with MS (pwMS), clinicians, policymakers and other stakeholders to make decisions about the use and reimbursement of rituximab as a disease-modifying therapy for people with relapsing or progressive forms of MS and to improve health equity for pwMS. Methods: An international multidisciplinary guideline development panel, appointed by MSIF, developed evidence-based recommendations through the GRADE Evidence-to-Decision (EtD) Framework. Results: The panel developed seven conditional recommendations for use of rituximab in low-resource settings. Recommendations favoured the use of rituximab for people with relapsing forms of MS and with active progressive forms of MS, compared to no treatment and to several on-label DMTs. Recommendations were based on very low certainty of the evidence. Conclusions: The available evidence, contextualised through the EtD Framework, provides a robust, transparent and viable case for health systems to provide and reimburse rituximab as a treatment for MS, particularly in low-resource settings.