We aimed to assess the difference in the efficacy and safety of the extended interval dosing (EID) regimen compared with the standard interval regimen (SID) of natalizumab for patients with multiple sclerosis (MS).

MS is an immune-mediated, chronic inflammatory disease of the central nervous system. Natalizumab is an approved monoclonal antibody against the a4ß1 integrin receptor for MS. The SID is once every four weeks as a 300 mg intravenous infusion. Extending the interval dosing of natalizumab beyond four weeks has been suggested for potential superiority in safety with preserved efficacy.

We searched PubMed, Scopus, WOS, Embase, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library for clinical trials published in English comparing EID with SID. We assessed the quality of the included studies using the Cochrane, National Institutes of Health (NIH), or Newcastle-Ottawa Scale (NOS) according to their study design. Our assessed outcomes were clinical relapse, MRI activity, expanded disability status scale (EDSS), annualized relapse rate (ARR), and progressive multifocal leukoencephalopathy (PML). The statistical analysis was conducted using Review manager software.

We included 13 studies; two RCTs, one switched single-arm trial, and the rest ten studies were observational. EID for 5-8 weeks was associated with a lower risk of newly enlarging T2 hyperintense lesions than SID (RR= 0.55, 95% CI [0.33, 0.94], p=0.03) and clinical relapse (RR=0.86, 95% CI [0.74, 0.99], p=0.04). However, no difference was detected between EID and SID in Gadolinium-enhancing lesions, ARR, PML, and EDSS.

Extending dosing intervals up to eight weeks did not diminish the effectiveness of natalizumab therapy, with a lower risk of clinical relapse and developing newly enlarging T2 hyperintense lesions. Well-conducted, longer studies, especially RCTs, are needed to produce more valid results.