Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial.

BACKGROUND AND OBJECTIVES: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID. METHODS: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated. RESULTS: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms. DISCUSSION: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.

Cryptococcal meningitis in a patient with multiple sclerosis on dimethyl fumarate treatment: A case report.

INTRODUCTION: We present a case of meningitis caused by Cryptococcus neoformans var. grubii in a 46-year old non-HIV-infected patient with multiple sclerosis, treated with dimethyl fumarate monotherapy. We identified no other risk factors for developing cryptococcal meningitis. The patient presented with a slowly progressive headache during preceding weeks and acute onset of confusion, nausea and vomiting. Clinical examination revealed intermittent disorientation without focal neurological symptoms. A lumbar puncture showed an opening pressure of > 50cmH2O. Diagnosis of cryptococcal meningitis was made after culture of Cryptococcus neoformans var. grubii of cerebrospinal fluid. CONCLUSION: This case emphasizes clinicians should bear in mind the possibility of cryptococcal meningitis in patients treated with dimethyl fumarate.