Personalized extended interval dosing of natalizumab in MS- a prospective multicenter trial.

Objective: We aimed to determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in relapsing remitting MS patients. Methods: This was a prospective multicenter single-arm trial with one year follow-up and a one year extension phase. Participants were adult persons with MS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received three monthly MRI scans, relapse assessments and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI, relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase. Results: Sixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5-7-week interval. No patient developed gadolinium enhancing lesions (95% CI 0 – 7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0 – 7.4%) or relapses (95% CI 0 – 7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, IQR 2.0-5.0) and after follow-up (3.0, IQR 2.0-5.0). Conclusion: Personalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable MS patients receiving personalized extended interval dosing based on individual natalizumab concentrations. Classification of evidence: This study provides class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable RRMS patients.