Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).

BACKGROUND: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals. METHODS: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID). RESULTS: Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI -4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy. CONCLUSIONS: MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks. TRIAL REGISTRATION NUMBER: NCT04225312.

Meralgia paresthetica: Nerve stimulator-guided injection with methylprednisolone/lidocaine, a double-blind randomized placebo-controlled study.

BACKGROUND: Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous nerve. A common therapy is injection with corticosteroids. The goal of this study was to analyze the effect of injection with methylprednisolone/lidocaine vs placebo. METHODS: After randomization, 10 patients received a nerve stimulator-guided injection with methylprednisolone/lidocaine, and 10 patients received saline. The primary outcome measure was pain (visual analogue scale, VAS). RESULTS: In the placebo group, there was a significant pain reduction (baseline VAS, 6.8; VAS week 12, 4.3; P = .014). The VAS score in the methylprednisolone group did not show a significant reduction (baseline VAS, 7.4; VAS week 12, 4.8; P = .053). There was no significant difference in pain reduction between the groups. CONCLUSIONS: We found no objective evidence for benefit from nerve stimulator-guided injection with corticosteroids in meralgia paresthetica, although this study is limited by a small sample size. Future placebo-controlled studies using ultrasound-guided injection are warranted.