Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis

• Published in: Multiple sclerosis 2024-08, Vol.30 (9), p.1163-1175
• Main Authors: Roos, Izanne, Sharmin, Sifat, Malpas, Charles, Ozakbas, Serkan, Lechner-Scott, Jeannette, Hodgkinson, Suzanne, Alroughani, Raed, Eichau Madueño, Sara, Boz, Cavit, van der Walt, Anneke, Butzkueven, Helmut, Buzzard, Katherine, Skibina, Olga, Foschi, Matteo, Grand’Maison, Francois, John, Nevin, Grammond, Pierre, Terzi, Murat, Prévost, Julie, Barnett, Michael, Laureys, Guy, Van Hijfte, Liesbeth, Luis Sanchez-Menoyo, Jose, Blanco, Yolanda, Oh, Jiwon, McCombe, Pamela, Ramo Tello, Cristina, Soysal, Aysun, Prat, Alexandre, Duquette, Pierre, Yamout, Bassem I, Khoury, Samia, van Pesch, Vincent, Macdonell, Richard, José Sá, Maria, Slee, Mark, Kuhle, Jens, Maimone, Davide, Spitaleri, Daniele LA, Willekens, Barbara, Asmi, Abdallah Al, Tallantyre, Emma, Robertson, Neil P, Coles, Alasdair, L Brown, J William, Kalincik, Tomas
• Format: Article
• Language: English
• Subjects: Adult; Alemtuzumab - adverse effects; Alemtuzumab - therapeutic use; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Cladribine; Cladribine - adverse effects; Cladribine - therapeutic use; Female; Fingolimod Hydrochloride - adverse effects; Fingolimod Hydrochloride - therapeutic use; Humans; Immunologic Factors - adverse effects; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Immunotherapy; Male; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab - adverse effects; Natalizumab - therapeutic use; Treatment Outcome
• ISSN: 1352-4585; 1477-0970; 1477-0970
• DOI: 10.1177/13524585241267211

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.