Natalizumab induced freedom from disease activity after failure to previous therapy in relapsing remitting multiple sclerosis.

Objectives: To analyze the efficacy of natalizumab after switching relapsing-remitting multiple sclerosis (RRMS) patients from other disease modifying treaments (DMTs).
Background: Natalizumab (Tysabri) is a monoclonal antibody directed against VLA4 that was recently approved for the treatment of RRMS. Due to safety concerns, the use should be restricted to highly active patients and/or patients with insufficient response to other DMTs. The pivotal trials were not designed to examine the effect of natalizumab as an escalation monotherapy.
Methods: Prospective, open label, observational study. All patients initiating natalizumab had experienced at least 1 relapse in the previous year under DMTs and had at least 1 Gd-enhancing lesion on their brain MRI. Previous treatment with interferon-beta (IFN-beta) or glatiramer acetate (GA) were stopped at least one week and azathioprine or mitoxantrone at least 3 months before switching. The minimum therapy duration with natalizumab was 6 months for all patients. 21 RRMS patients were included in this analysis. The mean age of the patients was 25,5 yo with mean disease duration of 6,8 years. All patients were under IFN-beta (17) or GA (4) during at least the previous year before starting natalizumab therapy. Four patients had also received azathioprine and 1 patient mitoxantrone.
Results: The mean relapse rate in the previous year was 2.15 (1-4), the mean EDSS at baseline was 3.3 (1,0-6.0), the mean number of Gd+ lesions at baseline 2,58 (1-6). Under tysabri treatment the annualized relapse rate dropped to 0,20. Eleven patients improved their EDSS (0,5 to 1,5 steps down), others remained stable at 6 months. The mean number of Gd+ T1 lesions dropped to 0,23 and the mean number of new T2 lesions was 0.25 on the control MRI at 6 months. 55% of patients were free from disease activity, i.e. had no relapses, no EDSS progression, no new T2 lesion and no Gd+ T1 lesions after 6 months of Tysabri. 5 patients experienced minor adverse events (1 zona, 2 flu-like symptoms, 1 gastroenteritis, 1 allergic reaction).
Conclusion: Natalizumab was well tolerated and safe as escalation therapy when previous DMTs had failed to control disease progression in this group of highly active RRMS patients. These results suggest comparable efficacy to the phase III AFFIRM trial of natalizumab when the drug is used in a context of breakthrough disease. Although data from preliminary analyses are promising, long term investigations are warranted.