Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis.

Zhu, Chao Zhou, Zhen Roos, Izanne Merlo, Daniel Kalincik, Tomas Ozakbas, Serkan Skibina, Olga Kuhle, Jens Hodgkinson, Suzanne Boz, Cavit Alroughani, Raed Lechner-Scott, Jeannette Barnett, Michael Izquierdo, Guillermo Prat, Alexandre Horakova, Dana Kubala Havrdova, Eva Macdonell, Richard Patti, Francesco Khoury, Samia Joseph Slee, Mark Karabudak, Rana Onofrj, Marco Van Pesch, Vincent [UCL] Prevost, Julie Monif, Mastura Jokubaitis, Vilija van der Walt, Anneke Butzkueven, Helmut MSBase Study Group et al.[show all]

(eng) BACKGROUND: To compare the effectiveness and treatment persistence of ocrelizumab, cladribine and natalizumab in patients with relapsing-remitting multiple sclerosis switching from fingolimod. METHODS: Using data from MSBase registry, this multicentre cohort study included subjects who had used fingolimod for ≥6 months and then switched to ocrelizumab, cladribine or natalizumab within 3 months after fingolimod discontinuation. We analysed relapse and disability outcomes after balancing covariates using an inverse-probability-treatment-weighting method. Propensity scores for the three treatments were obtained using multinomial-logistic regression. Due to the smaller number of cladribine users, comparisons of disability outcomes were limited to natalizumab and ocrelizumab. RESULTS: Overall, 1045 patients switched to ocrelizumab (n=445), cladribine (n=76) or natalizumab (n=524) after fingolimod. The annualised relapse rate (ARR) for ocrelizumab was 0.07, natalizumab 0.11 and cladribine 0.25. Compared with natalizumab, the ARR ratio (95% confidence interval [CI]) was 0.67 (0.47 to 0.96) for ocrelizumab and 2.31 (1.30 to 4.10) for cladribine; the hazard ratio (95% CI) for time to first relapse was 0.57 (0.40 to 0.83) for ocrelizumab and 1.18 (0.47 to 2.93) for cladribine. Ocrelizumab users had an 89% lower discontinuation rate (95% CI, 0.07 to 0.20) than natalizumab, but also a 51% lower probability of confirmed disability improvement (95% CI, 0.32 to 0.73). There was no difference in disability accumulation. CONCLUSION: After fingolimod cessation, ocrelizumab and natalizumab were more effective in reducing relapses than cladribine. Due to the low ARRs in all three treatment groups, additional observation time is required to determine if statistical difference in ARRs results in long-term disability differences.