Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis
Izanne Roos, Sifat Sharmin, Charles B. Malpas, Serkan Özakbaş, Jeannette Lechner‐Scott, Suzanne Hodgkinson, Raed Alroughani, Sara Eichau, Cavit Boz, Anneke van der Walt, Helmut Butzkueven, Katherine Buzzard, Olga Skibina, Matteo Foschi, François Grand’Maison, Nevin John, Pierre Grammond, Murat Terzi, Julie Prévost, Michael Barnett, Guy Laureys, Liesbeth Van Hijfte, José Luis Sánchez-Menoyo, Yolanda Blanco, Jiwon Oh, Pamela McCombe, Cristina Ramo‐Tello, Aysun Soysal, Alexandre Prat, Pierre Duquette, Bassem Yamout, Samia J. Khoury, Vincent Van Pesch, Richard Macdonell, María José Sá, Mark Slee, Jens Kühle, Davide Maimone, Daniele Spitaleri, Barbara Willekens, Abdallah Al Asmi, Emma Tallantyre, Neil P. Robertson, Alasdair Coles, J William L Brown, Tomáš Kalinčík
Abstract
Background: Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking. Objectives: To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS. Methods: Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab were identified in the global MSBase cohort and two additional UK centres. Patients were followed for ⩾6/12 and had ⩾3 in-person disability assessments. Patients were matched using propensity score. Four pairwise analyses compared annualised relapse rates (ARRs) and disability outcomes. Results: The eligible cohorts consisted of 853 (fingolimod), 464 (natalizumab), 1131 (ocrelizumab), 123 (alemtuzumab) or 493 (cladribine) patients. Cladribine was associated with a lower ARR than fingolimod (0.07 vs. 0.12, p = 0.006) and a higher ARR than natalizumab (0.10 vs. 0.06, p = 0.03), ocrelizumab (0.09 vs. 0.05, p = 0.008) and alemtuzumab (0.17 vs. 0.04, p < 0.001). Compared to cladribine, the risk of disability worsening did not differ in patients treated with fingolimod (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.47–2.47) or alemtuzumab (HR 0.73, 95% CI 0.26–2.07), but was lower for patients treated with natalizumab (HR 0.35, 95% CI 0.13–0.94) and ocrelizumab (HR 0.45, 95% CI 0.26–0.78). There was no evidence for a difference in disability improvement. Conclusion: Cladribine is an effective therapy that can be viewed as a step up in effectiveness from fingolimod, but is less effective than the most potent intravenous MS therapies.