Highlights
- •Cladribine (2-chloro-2′-deoxyadenosine) is an adenosine deaminase-resistant purine nucleoside analog with preferential lymphocyte reducing properties acting through the mode of pulsed immune reconstitution.
- •We focused on the effect of cladribine on oligoclonal bands (OCB) expression in the CSF in relapsing-remitting MS (RRMS) patients observed over 10 years.
- •Isoelectric focusing revealed that 55% of patients did not have OCB in CSF after cladribine treatment as compared to baseline testing when 100% of patients were positive for OCB.
- •At the last follow-up (Year 10), OCB-negative patients had lower disability compared to OCB-positive patients.
- •Cladribine-induced immune reconstitution leads to long lasting suppression of intrathecal humoral response, which might be an additional mechanism that enhances the therapeutic effect on disease progression in RRMS patients.
Abstract
Background
There has been long-term interest in cladribine as a drug for the treatment of MS.
The current study focused on the effect of cladribine on oligoclonal bands (OCB) expression
in the CSF in relapsing-remitting MS (RRMS) patients observed over 10 years.
Methods
29 treatment-naive subjects with RRMS were prospectively enrolled and received induction
therapy with subcutaneous parenteral cladribine (at a cumulative dose of 1.8 mg/kg;
divided into 6 courses every 5 weeks given for 4–6 days, depending on patients’ body
weight). Selected patients received maintenance doses in the follow-up period.
Results
Isoelectric focusing revealed that 55% of patients did not have OCB in CSF after cladribine
treatment as compared to baseline testing when 100% of patients were positive for
OCB. There were no significant differences in Expanded Disability Status Scale scores
at baseline and at the end of treatment cycle between OCB-positive vs. OCB-negative
subgroups. At the last follow-up, OCB-negative patients had lower disability compared
to OCB-positive patients (p = 0.03).
Conclusion
Cladribine-induced immune reconstitution leads to long lasting suppression of intrathecal
humoral response, which might be an additional mechanism that enhances the therapeutic
effect on disease progression in RRMS patients.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta.J. Neurol. Sci. 2006; 244: 97-102
- The treatment of chronic progressive multiple sclerosis with cladribine.Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 1716-1720
- Progression and CSF inflammation after eradication of oligoclonal bands in an MS patient treated with allogeneic hematopoietic cell transplantation for follicular lymphoma.Case. Rep. Neurol. 2012; 4: 101-106
- Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement.Arch. Neurol. 2005; 62: 865-870
- A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis.N. Engl. J. Med. 2010; 362: 416-426
- 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
- Cladribine to treat relapsing forms of multiple sclerosis.Neurotherapeutics. 2017; 14: 874-887
- 2-Chloro-2-deoxyadenosine–a novel immunosuppressive agent.Transplantation. 1993; 56: 1253-1257
- Effect of repeated treatments with cladribine (2-chlorodeoxyadenosine) on blood counts in multiple sclerosis patients.Arch. Immunol. Ther. Exp. (Warsz). 1995; 43: 323-327
- Cladribine treatment of multiple sclerosis.Lancet. 1994; 344: 537-538
- IgG production within the central nervous system: a critical review of proposed formulae.Ann. Neurol. 1985; 17: 13-20
- On the bioavailability of oral and subcutaneous 2-chloro-2′-deoxyadenosine in humans: alternative routes of administration.J Clin. Oncol. 1992; 10: 1514-1518
- Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness.J. Neuroimmunol. 2006; 180: 17-28
- Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: a longitudinal study.Mult. Scler. 2014; 20: 1900-1903
- Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis.Ann. Neurol. 2001; 50: 121-127
- Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.J. Neurol. Sci. 2013; 332: 35-40
- Intrathecal oligoclonal IgG synthesis in multiple sclerosis.J. Neuroimmunol. 2013; 262: 1-10
- Cladribine in treatment of chronic progressive multiple sclerosis.Lancet. 1994; 344: 9-13
- Effect of parenteral cladribine on relapse rates in patients with relapsing forms of multiple sclerosis: results of a 2-year, double-blind, placebo-controlled, crossover study.Mult. Scler. 2009; 15: 767-770
- A pilot trial of cladribine (2-chlorodeoxyadenosine) in remitting-elapsing multiple sclerosis.Med. Sci. Monit. 1998; 4: 4-8
- Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients.Mult. Scler. 2012; 18: 1038-1041
- Cladribine - an old newcomer for pulsed immune reconstitution in MS.Nat. Rev. Neurol. 2017; 13: 573-574
- A study of oligoclonal band negative multiple sclerosis.J. Neurol. Neurosurg. Psychiatry. 1996; 60: 27-30
Article info
Publication history
Published online: October 10, 2018
Accepted:
October 9,
2018
Received:
September 16,
2018
Identification
Copyright
© 2018 Published by Elsevier B.V.