To describe meningitis associated with ocrelizumab therapy

Ocrelizumab has received widespread use for both relapsing-remitting (RRMS) and primary-progressive MS (PPMS) after recent US market introduction in 2017. Unanticipated morbidities associated with ocrelizumab in "real world" populations outside clinical trials may further inform shared decision-making discussions with patients considering MS disease-modifying therapies.

Case report

Case 1: 70 year old female with PPMS, estimated EDSS 6.0, diagnosed 9 years prior who had received fingolimod for 3 months in 2014 as part of a clinical trial. Ocrelizumab had been initiated due to clinical progression 11 months prior to presentation with 24hrs of encephalopathy and fever. CSF protein was 282mg/dl, had 179 nucleated cells (83% lymphocytes) and remaining laboratory testing was negative. Brain MRI was unchanged from previous. Aseptic meningitis was diagnosed and recovery proceeded with conservative treatment. Case 2: 54 year old male with stable RRMS diagnosed 17 years prior, estimated EDSS 1.0, had previously received glatiramer acetate, then fingolimod in 2011 due to injection fatigue, and switched to ocrelizumab in 2017 due to safety concerns with fingolimod. He had received ocrelizumab for 12 months at the time of presentation of 1 week of headache, meningismus, and fever. CSF protein was 323 mg/dl and had 123 nucleated cells (66% lymphocytes). Lyme CSF IgG was reactive, but index was negative. Serum Lyme Ab was positive, but western blot negative. Additional infectious evaluation was negative. Aseptic meningitis was considered, but treatment for atypical Lyme meningitis presumed secondary to anti-CD20 therapy was pursued. Recovery proceeded after treatment with ceftriaxone.

We describe two cases of meningitis associated with ocrelizumab therapy in MS patients with very different phenotypes. Meningitis has been described in association with anti-CD20 therapies, but to our knowledge, these may be the first cases described in association with ocrelizumab.