Transitioning from sphingosine-1-phosphate modulators, such as fingolimod, to anti-CD20 therapies is common in patients with multiple sclerosis due to suboptimal disease control, progression, or family planning. However, the optimal washout period remains unclear, and cases of disease activity rebound following discontinuation of fingolimod have been documented. We present the case of a 43-year-old woman who developed severe rebound disease activity after transitioning from fingolimod to ofatumumab, despite a washout period of 28 days. The patient experienced a new lesion and neuropsychological impairment, which improved after treatment with high-dose methylprednisolone. Literature review highlights the complexity of factors influencing rebound, including washout duration, lymphocyte count, and disease control during fingolimod therapy. Evidence suggests that initiating ofatumumab treatment without a prolonged washout period may mitigate rebound risk
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