International Expert Opinion on Optimal Switching to Cladribine Tablets from Other High-Efficacy Disease-Modifying Therapies for Relapsing–Remitting Multiple Sclerosis: Opportunities and Challenges

Relapsing multiple sclerosis (RMS) is a chronic inflammatory disease usually diagnosed at a young age. Most patients receive several disease-modifying therapies (DMTs) over time, but evidence-based guidelines to support treatment sequencing are limited, particularly for switches between high-efficacy DMTs. An international group of experts in the care of RMS reviewed the current evidence and their clinical practice in order to provide recommendations on the optimal therapeutic use of cladribine tablets (CladT, an immune reconstitution therapy for RMS) in patients previously managed on anti-trafficking agents (S1P modulators, natalizumab) or an anti-CD20 agent. Recommendations relate to switching due to breakthrough RMS disease activity or safety/tolerability issues, to reduce the risk of safety concerns, including de-risking in older people with stable RMS, and to facilitate family planning. We propose that CladT is a rational option for people with RMS presenting with intractable safety/tolerability issues during treatment with a high-efficacy DMT, for older patients with stable RMS who have received long-term DMT, or for patients with breakthrough RMS disease activity despite treatment with an S1P modulator. In selected cases, CladT may be considered for patients with breakthrough RMS disease activity on anti-CD20 treatment. It is important to keep the interval between withdrawal of a previous anti-trafficking DMT (especially S1P modulators) and initiation of CladT as short as possible if the switch is intended to address breakthrough RMS disease activity, especially with regard to the prevention of rebound RMS disease activity. Immune reconstitution therapy with CladT may also provide an opportunity to plan for pregnancy in the absence of continuous DMT.