Cladribine versus fingolimod,natalizumab and interferon β for multiple sclerosis

Abstract

Objective:

This propensity score–matched analysis from MSBase compared the effectiveness of cladribine with interferon β, fingolimod or natalizumab.

Methods:

We identified all patients with relapse-onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase. Three pairwise propensity score–matched analyses compared treatment outcomes over 1 year. The outcomes were hazards of first relapse, disability accumulation and disability improvement events. Sensitivity analyses were completed.

Results:

The cohorts consisted of 37 (cladribine), 1940 (interferon), 1892 (fingolimod) and 1410 patients (natalizumab). The probability of experiencing a relapse on cladribine was lower than on interferon (p = 0.05), similar to fingolimod (p = 0.31) and higher than on natalizumab (p = 0.042). The probability of disability accumulation on cladribine was similar to interferon (p = 0.37) and fingolimod (p = 0.089) but greater than natalizumab (p = 0.021). The probability of disability improvement was higher on cladribine than interferon (p = 0.00017), fingolimod (p = 0.0025) or natalizumab (p = 0.00099). Sensitivity analyses largely confirmed the above results.

Conclusion:

Cladribine is an effective therapy for relapse-onset multiple sclerosis. Its effect on relapses is comparable to fingolimod and its effect on disability accrual is comparable to interferon β and fingolimod. Cladribine may potentially associate with superior recovery from disability relative to interferon, fingolimod and natalizumab.

Keywords

Cladribine interferon fingolimod natalizumab relapses disability

Get full access to this article

View all access options for this article.

References

Beutler

Cladribine (2-chlorodeoxyadenosine). Lancet 1992; 340: 952–956.

Juliusson

Lenkei

Liliemark

Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: Phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine. Blood 1994; 83: 3672–3681.

Rice

Filippi

Comi

Cladribine and progressive MS: Clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI study group. Neurology 2000; 54: 1145–1155.

Giovannoni

Comi

Cook

et al . A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 2010; 362: 416–426.

Kalincik

Lizak

Jokubaitis

et al . Australian cladribine experience. In: Proceedings of the 32nd conference of the European Committee for Treatment and Research in Multiple Sclerosis, London, 14–17 September 2016.

Kalincik

Horakova

Spelman

et al . Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol 2015; 77: 425–435.

Kalincik

Brown

JWL

Robertson

et al . Comparison of alemtuzumab with natalizumab, fingolimod, and interferon beta for multiple sclerosis: A longitudinal study. Lancet Neurol 2017; 16: 271–281.

Butzkueven

Chapman

Cristiano

et al . MSBase: An international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler 2006; 12: 769–774.

Polman

Reingold

Edan

et al . Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald criteria’. Ann Neurol 2005; 58: 840–846.

10.

Polman

Reingold

Banwell

et al . Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.

11.

Kalincik

Kuhle

Pucci

et al . Data quality evaluation for observational multiple sclerosis registries. Mult Scler 2017; 23: 647–655.

12.

Kalincik

Cutter

Spelman

et al . Defining reliable disability outcomes in multiple sclerosis. Brain 2015; 138: 3287–3298.

13.

R Development Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2011.

14.

Rosenbaum

Rubin

DB.

Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc 1984; 79: 516–524.

15.

Kalincik

Butzkueven

Observational data: Understanding the real MS world. Mult Scler 2016; 22: 1642–1648.

16.

Rosenbaum

PR.

Observational studies. 2nd ed. New York: Springer, 2002.

17.

Giovannoni

Cook

Rammohan

et al . Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: A post-hoc and subgroup analysis. Lancet Neurol 2011; 10: 329–337.

18.

Giovannoni

Comi

Cook

et al . Clinical efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis (RRMS): Final results from the 120-week phase IIIb extension trial to the CLARITY study (P3.028). Neurology 2016; 86: P3028.

19.

Montalban

Cohen

Leist

et al . Efficacy of cladribine tablets as add-on to IFN-beta therapy in patients with active relapsing MS: Final results from the phase II ONWARD study. Neurology 2016; 86: P3029.

20.

Leist

Comi

Cree

et al . Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): A phase 3 randomised trial. Lancet Neurol 2014; 13: 257–267.

21.

Belachew

Phan Ba

Bartholome

et al . Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Eur J Neurol 2011; 18: 240–245.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.17 MB

0.23 MB