Prospective, Longitudinal Study of Natalizumab Treatment in MS Patients

Background: The efficacy of natalizumab, a selective alpha-4 integrin antagonist that prevents leukocyte migration into the central nervous system and subsequent inflammatory activity, was demonstrated in relapsing-remitting MS (RRMS) patients in the 2-year randomized, controlled AFFIRM trial. Real-world data are needed to confirm the efficacy and safety of natalizumab in a clinical setting and beyond 2 years of treatment.

Objectives: To evaluate the efficacy of long-term natalizumab treatment in MS patients in a clinical setting.

Methods: Patients (N=133) were enrolled consecutively into this open-label, single-center, prospective, observational study. Efficacy parameters included relapse rate, MRI results, and Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) scores. Data on laboratory results, adverse events, 9-hole peg test, cognitive function, and fatigue were also collected.

Results: At the time of these preliminary analyses, patients had received a median of 23 cumulative natalizumab doses. Most patients were female (77%); the average age was 44.3 years. Most patients (82%) had RRMS (smaller proportions had other MS forms); 23% had a history of prior immunosuppression or chemotherapy. More than a third (39.4%) of patients had a history of at least 1 relapse in the year prior to natalizumab treatment initiation; nearly half (48.2%) had a history of new gadolinium-enhancing (Gd+) lesions within 18 months prior to natalizumab treatment. After a median of 23 cumulative doses of natalizumab, clinical relapse was experienced by 4 patients; 3 of the 4 were positive for anti-natalizumab antibodies. The overall percentage of patients with new Gd+ lesions during the study was 3%. The mean EDSS score decreased significantly over time (3.6 at baseline vs 3.0 on treatment; P=0.0094). Results for T25FW also decreased significantly over time (8.1 seconds at baseline vs 7.6 seconds on treatment; P=0.0005).

Conclusions: In this cohort of MS patients with active disease at baseline, as evidenced by prior treatments, relapses, and MRI lesions, natalizumab treatment was associated with substantial improvement in clinical and radiological parameters. Additional and finalized efficacy and safety data on patients treated with natalizumab for up to 6 years will be presented. This analysis will provide useful information on the long-term efficacy and safety of natalizumab treatment in a real-world clinical setting.