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.