TY - JOUR
T1 - Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis
AU - Zhu, Chao
AU - Zhou, Zhen
AU - Roos, Izanne
AU - Merlo, Daniel
AU - Kalincik, Tomas
AU - Ozakbas, Serkan
AU - Skibina, Olga
AU - Kuhle, Jens
AU - Hodgkinson, Suzanne
AU - Boz, Cavit
AU - Alroughani, Raed
AU - Lechner-Scott, Jeannette
AU - Barnett, Michael
AU - Izquierdo, Guillermo
AU - Prat, Alexandre
AU - Horakova, Dana
AU - Kubala Havrdova, Eva
AU - Macdonell, Richard
AU - Patti, Francesco
AU - Khoury, Samia Joseph
AU - Slee, Mark
AU - Karabudak, Rana
AU - Onofrj, Marco
AU - Van Pesch, Vincent
AU - Prevost, Julie
AU - Monif, Mastura
AU - Jokubaitis, Vilija
AU - Van Der Walt, Anneke
AU - Butzkueven, Helmut
AU - MSBase Study Group
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - multiple sclerosis
KW - neuroimmunology
UR - http://www.scopus.com/inward/record.url?scp=85141936081&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2022-330104
DO - 10.1136/jnnp-2022-330104
M3 - Article
C2 - 36261289
AN - SCOPUS:85141936081
SN - 0022-3050
VL - 93
SP - 1330
EP - 1337
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 12
ER -