Therapeutic efficacy of natalizumab (Tysabri) in MS patients with high disease activity: a Danish nationwide study Annette Oturai1, Thor Petersen2, Nils Koch-Henriksen3, Poul Erik Hyldgaard Jensen1, Finn Sellebjerg1, Per Soelberg Sorensen1 1 The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark; 2Department of Neurology, Aarhus University Hospital, Aahus, Denmark; 3Department of Neurology, University Hospital in Aalborg, Aalborg, Denmark
Background: Previous studies on the effect of Tysabri in multiple sclerosis (MS) patients have included patients with moderate disease activity. According to Danish regulatory provisions, Tysabri can only be administered to patients with two or more relapses on disease-modifying therapy (DMT) in the previous year. The effect of Tysabri in a patient population with high disease activity has not previously been reported.
Objective: To evaluate the therapeutic effect of Tysabri in MS patients with high disease activity. Methods: Since 1996 the Danish MS Treatment Register has prospectively collected clinical data on all patients on DMT. We analyzed data from the first 173 consecutive Tysabri-treated patients, observed for at least 24 weeks. We measured Tysabri-binding antibodies at month 3, 6 and 12.
Results: Baseline data at onset for the 173 Tysabri treated patients were female:male ratio 2.15:1, median age 40 (range 18–64) years, disease duration 8.0 (0–36) years, and Expanded Disability Statuas Scale score 4.5 (0–8). A total of 167 patients (96.5%) had previously received DMT, of whom 35 (21%) had been treated with mitoxantrone. An interim analysis after a mean observation time of 6.2 months (range 2.1 - 14.6) showed an annualized relapse rate of 0.76 compared to a rate of 2.4 (p < 0.0001) in the 12 months preceding Tysabri treatment. We did not observe any opportunistic infections. Four allergic reactions were reported, but there were no severe reactions. Of 110patients 9 (8%) were tested positive for Tysabri-binding antibodies at week 12.
Conclusions: Tysabri appears to be effective in MS patients with high disease activity as the annual relapse rate dropped from 2.40 to 0.76, but the relapse rate was higher than the 0.26 reported in the AFFIRM study after the first treatment year. This is likely to reflect differences in disease activity before the initiation of Tysabri treatment.