A new narrative review published in Neurology: Neuroimmunology & Neuroinflammation combines mechanistic and real-world evidence to guide health care professionals through common scenarios that prompt a treatment switch in multiple sclerosis (MS) patients. The review focuses on switching disease-modifying therapies (DMTs) in the “hit-hard-and-early” treatment era.
Sequencing After Sequestration Therapies
Natalizumab (Tysabri; Biogen) and the sphingosine-1-phosphate receptor modulators (S1PRMs) work by trapping lymphocytes outside the central nervous system. The authors found that switching to an anti-CD20 monoclonal antibody after either agent produced better control of relapses and MRI activity than switching to another S1PRM.
Keeping the transition interval under 30 days was associated with the lowest rates of breakthrough disease. Waits of 30 days or longer were linked to relapse rates as high as 16%.
Cladribine (Mavenclad; EMD Serono) emerged as a reasonable option after an S1PRM, particularly for patients prioritizing a favorable pregnancy-planning profile. However, the authors caution that delaying cladribine to await lymphocyte recovery may do more harm than good.
Related: User Account Blocked by Social Media Platform
Anti-CD20 and Cladribine as Exit Strategies
For patients well controlled on anti-CD20 therapy but developing hypogammaglobulinemia or recurrent infections, the review points to cladribine as a promising off-ramp. Cladribine may normalize immunoglobulin levels and lymphocyte counts, offering an alternative to simply extending dosing intervals.
Conversely, patients who experience breakthrough activity within a cladribine treatment cycle are generally better served by escalating to a monoclonal antibody instead of repeating cladribine. Recurrence within the 4-year cycle suggests the immune reconstitution approach has not achieved its goal.
BTK Inhibitors
The review looks forward to Bruton tyrosine kinase inhibitors (BTKis), an emerging class with distinct efficacy profiles. Because BTKis lack the immune-depleting properties needed to counter rebound activity, the authors suggest they are unlikely to work well as a direct switch from sequestration agents.
Instead, current evidence points toward BTKis functioning as maintenance therapy layered on after an initial depleting agent, targeting the smoldering, compartmentalized inflammation that drives disability progression independent of relapse.
Related: Users Blocked by Website Security Filter
The review’s emphasis on transition timing, immune monitoring, and individualized risk-benefit tradeoffs lands squarely in pharmacists’ scope of practice. Neurology and specialty pharmacists are frequently the team members tracking infusion schedules, lymphocyte and immunoglobulin trends, and John Cunningham virus antibody index results.
They are also positioned to counsel patients through the anxiety that can accompany a therapy switch, particularly around infection risk during washout periods and family-planning timelines that intersect with teratogenicity windows for certain agents.
As MS treatment increasingly relies on sequencing strategies that anticipate future switches from the outset, pharmacists’ ongoing relationships with patients—paired with their expertise in pharmacokinetics, monitoring parameters, and drug interactions—make them essential partners in translating evidence into individualized care plans.
