The multiple sclerosis (MS) treatment landscape has expanded over time, becoming increasingly complex with the availability of more advanced high-efficacy therapies (HETs). In this evolving context, shared decision-making (SDM) between healthcare providers (HCPs) and patients is crucial for optimizing treatment and ensuring personalized care. Cladribine tablets (CladT), a highly effective therapy with a well-established safety profile, are approved in the USA for treating adults with relapsing MS, including those aged ≥ 50 years. Globally, more than 89,000 patients have received CladT. HCPs have considered transitioning patients from HETs, such as anti-CD20 monoclonal antibodies, to CladT. Further research is needed to understand factors influencing the decision to switch from an anti-CD20 therapy to CladT. This podcast explores real-world insights and challenges from USA-based advanced practice providers who have switched patients with MS from anti-CD20 therapies to CladT. The discussion builds on the results from a real-world retrospective survey of 100 HCPs aimed at understanding their rationale for transitioning patients from anti-CD20 therapies (e.g., ocrelizumab, ofatumumab, rituximab, ublituximab) to CladT. The survey also assessed differences in rationale for discontinuing anti-CD20 therapies and switching from anti-CD20 therapies to CladT between patients aged < 50 and ≥ 50 years. Findings revealed that the most common reasons for transitioning from anti-CD20 therapy to CladT included perception of increased efficacy on relapses (55%) and disability progression (54%), while common reasons for discontinuing anti-CD20 therapy included relapses (41%) and continued clinical activity (26%). In patients aged > 50 years, desire to avoid long-term immunosuppression (45%) was a key factor in choosing CladT after anti-CD20 therapy. Notably, AEs suggestive of immunosuppression or opportunistic infections were not reported in patients who transitioned to CladT, and no new safety signals, infections, or immunoglobulin reductions were observed. This podcast also highlights the economic benefits of CladT, the role of SDM, and recommendations based on clinical experiences. Podcast Transcript (MP4 217843 kb).