Review of Guidelines on Second-Line Therapy for Patients With Relapsing-Remitting Multiple Sclerosis: A 2024 Update

What Is the Issue? Multiple sclerosis is a chronic autoimmune disorder that causes damage to central nervous system cells. Relapsing-remitting multiple sclerosis is characterized by relapses (episodes of new or worsening symptoms) followed by periods of partial or complete recovery (remission). First-line therapies for multiple sclerosis include interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. Second-line therapies include natalizumab, alemtuzumab, and fingolimod. The considerations for switching from a first-line to a second-line therapy for patients with relapsing-remitting multiple sclerosis are unclear. What Did We Do? To inform decisions around switching patients with relapsing-remitting multiple sclerosis from a first-line to a second-line therapy, we sought to identify and summarize recommendations from evidence-based guidelines. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included guidelines, and narratively summarized the findings. What Did We Find? We identified 2 evidence-based guidelines that included recommendations around switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis. One guideline from Spain classified therapies as moderate-efficacy (interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide) and high-efficacy (fingolimod, cladribine, ocrelizumab, natalizumab, and alemtuzumab). The guideline recommends that patients switch from a moderate-efficacy disease-modifying therapy to a high-efficacy disease-modifying therapy for a variety of reasons including suboptimal response, adverse events, comorbidities, pregnancy plans, confirmed progression of disability, and tolerability issues. The guideline also included several recommendations specific to switching to natalizumab as well as washout periods when switching from a moderate-efficacy therapy. One guideline from France included recommendations regarding washout periods for switching from a first-line therapy. The guideline recommends that when switching from a first-line therapy, a second-line therapy or an induction therapy could be started without a washout period if the patient has normal biological results. The guideline also recommends validating the indication, timing, and washout period of a switch to a second-line therapy or induction therapy with a multiple sclerosis expert centre or in a multidisciplinary consensus meeting. The guideline also included specific considerations for washout periods for dimethyl fumarate and teriflunomide. What Does It Mean? The considerations for switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis — including the timing of a switch, choice of second-line therapy, and washout periods — depend on treatment response, individual patient characteristics, and the specific first-line therapy being used. Additional evidence-based guidelines that use comprehensive methods for identifying evidence and include clear links between identified evidence and recommendations will help to reduce uncertainty around considerations for switching from first-line to second-line therapies in patients with relapsing-remitting multiple sclerosis.