Early Natalizumab Treatment for Multiple Sclerosis May Have Greater Benefit

Late initiation of natalizumab in patients with MS is associated worse disease progression compared with patients who started treatment earlier.

Earlier initiation of natalizumab in patients with multiple sclerosis (MS) is associated with superior functional and brain-related outcomes, according to study findings published in Multiple Sclerosis and Related Disorders.

Many disease-modifying therapies (DMTs) for MS have been developed over the past 25 years. Although there are numerous options for patients, which DMT is most effective for each patient, the timing of DMT initiation, and the sequence of DMTs remain open areas of research.

For this study, researchers sourced data from Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) and Tysabri Outreach: Unified Commitment to Health Prescribing Program (TOUCH) to evaluate the effect of earlier or later start of natalizumab among patients with MS. Data were collected for this study at 10 sites in the United States, Germany, and Spain. Outcomes were measured using magnetic resonance imaging (MRI), Patient-Derived Disease Steps (PDDS), Processing Speed Test (PST), Walking Speed Test (WST), and Manual Dexterity Test (MDT).

A total of 661 patients received natalizumab. The patients were median aged 32 (range, 14-59) years at diagnosis, 74.1% were women or girls, 76.7% were White, and patients received their first infusion at age 38.2 (range, 18.1-70.3) years.

This suggests that there is a window of opportunity to prevent disability accumulation, after which future disability is already determined.

Stratified by quintile of time of natalizumab initiation, 133 started treatment 0.1-1.3 years after diagnosis, 132 started treatment at 1.3-3.1 years, 132 started treatment at 6.3-10.0 years, and 132 started treatment at 10.0-19.8 years.

Starting natalizumab treatment later associated with decreased walking speed (P <.001), longer processing speed (P <.001), poorer manual dexterity (P <.001), more brain atrophy (P =.001), and greater T2 lesion volumes (P =.020).

Among only the subset of patients diagnosed in 2006 or after (n=424), later natalizumab treatment start assoicated with decreased walking speed (P =.037), longer processing speed (P <.001), and poorer manual dexterity (P <.001). No significant differences in brain atrophy or T2 lesion volumes were observed in this cohort on the basis of natalizumab timing.

The major limitation of this study was that it was not possible to match disease characteristics with the timing of natalizumab initiation.

The researchers concluded that a later initiation of high-efficacy DMTs for MS is associated with worse long-term outcomes, and rather, high-efficacy DMTs may provide a greater benefit when initiated earlier. “This suggests that there is a window of opportunity to prevent disability accumulation, after which future disability is already determined,” they wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Ontaneda D, Mowry EM, Newsome SD, et al. Benefits of early treatment with natalizumab: a real-world study. Mult Scler Relat Disord. Published online October 3, 2022. doi:10.1016/j.msard.2022.104216