Cladribine Tablets: A Review in Relapsing MS

Abstract

Cladribine is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, key cells underlying multiple sclerosis (MS) pathogenesis. Cladribine tablets (Mavenclad) represent the first short-course oral disease-modifying drug (DMD) for use in MS. The tablets, administered in two short courses 1 year apart, are indicated for the treatment of adults with highly active relapsing MS on the basis of data from pivotal clinical trials, including the phase 3 study CLARITY and its extension. A cumulative cladribine tablets dose of 3.5 mg/kg administered in this fashion in CLARITY reduced clinical relapse, disability progression and MRI-assessed disease activity and also improved some aspects of health-related quality of life (HR-QOL) versus placebo over 96 weeks in adults with relapsing-remitting MS (RRMS). Moreover, in the 96-week extension (plus 24 weeks' supplemental follow-up), no additional clinical benefit was gained from continuing versus discontinuing cladribine tablets after the first two annual courses of therapy, although MRI activity was more notable in a subset of cladribine tablet recipients who discontinued the drug. In post hoc analyses of CLARITY and/or a phase 2b trial, benefits of cladribine tablets were seen in patients with high disease activity (HDA) relapsing MS that were sometimes greater than in patients without HDA. Cladribine tablets have an acceptable tolerability profile and do not appear to be associated with an increased risk of overall infection or with an increased risk of malignancy (vs. matched reference populations). Active comparisons and longer-term follow-up would be beneficial, although current data indicate that for adults with highly active relapsing MS, cladribine tablets are an effective treatment option with the convenience of low-burden, short-course, oral administration.

The association between multiple sclerosis and pain medications

“…More recent developments in MS treatment include treatments such as Cladribine, which is believed to be beneficial for patients with highly active RR MS in particular 80 .…”

“…Cladribine is a deoxyadenosine analogue which reduces the pro-inflammatory response through depleting lymphocytes 80 . Teriflunomide is another anti-inflammatory medication used in MS, in which the proliferation of rapidly dividing cells, including activated lymphocytes, is inhibited 81 .…”

<p>Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis</p>

“…It was identified as an anticancer drug for the treatment of B and T cell lymphoid malignancies, but was later used for the treatment of RRMS due to its immunosuppressive activity for these immune cells that play a significant role in MS pathogenesis. 114 Regarding its effects on the chemokine system of MS patients, it was demonstrated that treatment of RRMS patients with Cladribine resulted in declined levels of CXCL8 in their CSF, and a significant decrease in CCL5 levels in the CSF and serum of those patients. 115 Effects of Natalizumab on Chemokines and Chemokine Receptors Natalizumab (Tysabri) is a humanized monoclonal antibody that selectively binds to α4 integrins expressed on the surface of human leukocytes.…”

Management of relapsing–remitting multiple sclerosis in Qatar: an expert consensus

“…Treatment with cladribine tablets is relatively well tolerated by people with RRMS; its main side-effects are lymphopenia/leukopenia and opportunistic infections, mainly herpes zoster, according to published information 45,46 , its European labelling and the experience of physicians. Cladribine tablets do not appear to be associated with increased risk of PML 46 , although their European labelling contains a note that PML has occurred in patients taking a different cladribine regimen for the treatment of leukaemia.…”