Cladribine: Off-label disease modification for people with multiple sclerosis in resource-poor settings?

Abstract

BackgroundA considerable number of people with multiple sclerosis (pwMS) live in low- and middle-income countries (LMIC), where lack of resource adversely affects access to effective disease-modifying treatment.ObjectiveThe objective of this commentary is to propose a useful cost-effective disease-modifying treatment option for pwMS in LMIC with potential high efficacy and high convenience to the pwMS and treating physician.Viewpoint: We propose using generic 2-chloro-2’-deoxyadenosine (cladribine), a small molecule licensed for treatment of people with hairy cell leukaemia, as a solution of this significant equity imbalance. Cladribine has been shown in phase II and III trials to be a highly effective disease-modifying treatment for pwMS, and its adverse effect profile is comparable with any DMT currently licensed in high-income economies where an oral preparation has recently been licensed by the European Medicines Agency.ConclusionOur viewpoint takes into account experience we have gathered over the past three years in the use of generic cladribine to treat pwMS. Whilst here we focus on MS, there is significant potential for use of cladribine in other conditions that could benefit from its mechanism of action.

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

“…This single-center case series illustrated our experience using intravenous cladribine to treat RMS patients and early SPMS patients. Overall, cladribine has been shown to be effective for the treatment of early and late relapsing MS but is not commonly used for MS treatment, which is consistent with what has been reported in the clinical trial data [11]. Due to a good safety profile, cladribine is comparable to other chemotherapeutic agents used to treat MS, such as mitoxantrone.…”

“…Though oral cladribine is currently approved for the treatment of RRMS, this study supported the use of parenteral cladribine for the treatment of SPMS patients. Positive outcomes in this study suggest that parenteral cladribine could be used as a relatively inexpensive alternative MS treatment, particularly in poor populations with limited access to more expensive and riskier MS treatment options, such as mitoxantrone, which costs $429 USD in the United Kingdom per month and $908 USD in the United States per month [11].…”

“…These results were similar to the efficacy and safety profile of the recently approved oral form of cladribine. The dosing regimen used in our study (0.0875 mg/kg/day for four days every six months) was parenterally equivalent to the approved tablet form in terms of absorption, distribution, and bioavailability [11]. Oral cladribine bioavailability is between 37% and 51%, with approximately 20% of cladribine bound to plasma proteins [12].…”

“…Recent approval of cladribine tablets was based on efficacy shown in three Phase 3 clinical trials (CLARITY (NCT00213135), CLARITY Extension (NCT00641537), and ORACLE MS (NCT00725985)), in addition to over a decade of accumulated safety data from all MS patients exposed to cladribine in either parenteral or oral form (Premiere Registry, Premier, Inc., Charlotte, NC, USA), which clearly failed to demonstrate any substantial malignancy risk [9]. Post hoc analysis of CLARITY and CLARITY Extension showed up to 90% of patients were free of new lesions as demonstrated by MRI, and up to 81% of MS patients remained relapse-free four years after treatment with cladribine tablets, regardless of cumulative dose [10][11].…”

The role of B cells in multiple sclerosis: Current and future therapies

“…B and T cells express low levels of 5'-NTase relative to DCK 245 . Previous reports emphasized the primary target population as T cells, however the depletion of B cells is comparatively greater 245,246 . This selectivity is likely due to the finding that most B cell subsets express higher concentrations of DCK compared with T cells 245 .…”