8. Natalizumab de-escalation to interferon beta-1b in multiple sclerosis patients

Abstract

Background Natalizumab (NAT) discontinuation leads to multiple sclerosis reactivation. Objective To explore the concept of natalizumab de-escalation to interferon beta-1b (IFNB-1b) compared to continued treatment with NAT. Methods One year, randomized, rater-blinded, parallel-group, pilot study. RRMS patients on NAT for >12 months and clinically stable (free from relapses and disability progression for >6 months, without enhancing lesions [CEL] at baseline MRI) were randomized to NAT or IFNB-1b. Primary endpoint was time to first on-study relapse. Secondary endpoints were frequency of relapse free patients, number of relapses per patient, number of new/enlarging T2 (NT2) lesions and CEL at months 3, 6, 9 and 12 vs baseline (BL). Analyses are based on the intention to treat population. Results Nineteen patients were included (NAT n = 10; IFNB-1b n = 9) having comparable baseline characteristics. Time to first on study relapse showed a trend favouring NAT without reaching significance (p = 0.125, log-rank test). Among secondary clinical and radiological outcomes, the majority showed a trend favouring NAT without reaching significance except for number of NT2 lesions at month 6 being significantly higher in the IFNB-1b group (p = 0.043, U-Mann Whitney). Adverse events were within the expected range. Conclusions Our results suggest no pronounced inflammatory activity after de-escalation of NAT to IFNB-1b and indicate that the concept should be evaluated further.