Serum sickness (SS) is a rare hypersensitivity reaction that can occur with monoclonal antibodies, and only 1 case of SS has been reported with ocrelizumab. We describe 2 patients with multiple sclerosis (MS) who developed SS/SS-like reactions (SSLRs) following ocrelizumab infusions. A man, aged 45 years, and a woman, aged 59 years, both with primary progressive MS, developed generalized weakness and arthralgias following their ocrelizumab infusions. Brain and spinal cord MRIs revealed no new or enhancing demyelinating lesions in both cases. They both had elevated inflammatory markers and negative infectious workups. They were subsequently treated for presumed SS with a steroid taper (and with potent anti-inflammatories in the second case), and symptoms improved dramatically after a few days. These cases suggest that SS/SSLRs should be suspected in a patient with new-onset arthralgia following ocrelizumab infusion who has an otherwise negative workup and rapid response to steroids.

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