Efficacy and Safety of Intravenous Cladribine in Patients with Rapidly Evolving or Early Secondary Progressive Multiple Sclerosis.

Foziah Alshamrani,Mohammed F Almuaigel,Hind Alnajashi

doi:10.7759/cureus.6995

Abstract

BackgroundMultiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). The etiology of the disease remains unknown. Multiple theories highlight genetic, environmental, and infectious factors that may a role. MS is considered as the main cause of disability in young people. Cladribine, known chemically as (2-Chloro-2′-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas. The goal of this study was to evaluate the safety and efficacy of cladribine in patients with rapidly evolving or early secondary progressive MS.MethodsThis observational, single-center, retrospective chart review at the MS Clinic in the Ottawa General Hospital, Ottawa, Canada. A total of 24 patients (median Expanded Disability Status Scale (EDSS) of 4.5) received cladribine (0.07 mg/kg/day) for four consecutive days every six months for ≥ 2 cycles with further cycles depending on lymphocyte recovery or disease activity to a maximum of eight cycles from 2005 until 2016 were included. Four patients who were already diagnosed with rapidly evolving or early secondary progressive multiple sclerosis (SPMS) were induced with cladribine. We evaluated relapse, EDSS, and magnetic resonance imaging (MRI) results.ResultsOut of 24 patients (ages ranging from 30 - 60), 80% were female. Median follow-up time was seven years. The mean relapse rate in the two years before patients were given cladribine was 1.25. Twenty patients had previously received multiple disease-modifying therapies (DMTs) (≥ 2) prior to receiving cladribine. Following cladribine, eight patients suffered 10 relapses (33.3% of the cohort). Annualized relapse rates (ARRs) were reduced from 1.25 to 0.42, which was statistically significant (p-value = 0.002). There was no mean difference in EDSS (p-value = 0.06): 16% deteriorated, 62% did not change, and 12.5% improved. New MRI activity (new T2 or Gad+ lesions) was noted in only seven of 24 patients. ConclusionParenteral cladribine reduced the relapse rate from 1.25 to 0.42, which was statistically significant (p-value = 0.002). MRI activity in patients with rapidly evolving or early secondary progressive multiple sclerosis had a reasonable safety profile.

Highlights

Cladribine is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas known chemically as (2-Chloro-2′-deoxyadenosine) [1]
Cladribine was generally well-tolerated by secondary progressive multiple sclerosis (SPMS) patients and may be a suitable substitute for other chemotherapeutic agents, such as mitoxantrone, due to its superior safety profile, which is consistent with what has been reported in the clinical trial data
Yildiz et al found that cladribine may be an effective treatment option for individuals with nonrelapsing deteriorating progressive multiple sclerosis as determined by the reduction of disease activity [14]. This retrospective observational study with low patient numbers provides some evidence about the realworld tolerability of cladribine

Summary

Introduction

Cladribine is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas known chemically as (2-Chloro-2′-deoxyadenosine) [1]. Cladribine causes prolonged profound lymphopenia affecting both T-cells (CD4+, CD8+) and B-cells (CD19+) [3]. Parenteral cladribine has been approved for the treatment of malignancies, such as hairy-cell leukemia [1]. Cladribine has been used clinically for more than three decades in oncology populations [4]. It has been investigated as a treatment for several autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and glomerulonephritis [5,6]. Multiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). Cladribine, known chemically as (2-Chloro-2′-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas.

Objectives

Methods

Results

Discussion

Conclusion