Cost-effectiveness of cladribine tablets, alemtuzumab, and natalizumab in the treatment of relapsing-remitting multiple sclerosis with high disease activity in England

Abstract

Aims: Cladribine tablets were the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England.

Materials and methods: A cohort-based Markov model with 11 health states (10 Expanded Disability Status Scale [EDSS] plus death) was developed. Transition matrices from the British Columbia registry were used to model the natural history of EDSS. The treatment effect on EDSS was modelled using hazard ratios for 6-month confirmed disability progression from an indirect treatment comparison (ITC). Relapses and drug-related adverse events were modeled via annualized relapse rates and event probabilities, with associated costs and quality-adjusted life year (QALY) losses. Utilities were derived from trials and the literature, and costs from NHS and literature sources. Uncertainty was assessed via probabilistic and deterministic sensitivity analyses.

Results: Cladribine tablets were dominant (i.e., less costly and more effective) vs alemtuzumab and natalizumab in pairwise comparisons, and the dominant strategy in fully incremental analyses. Incremental cost was driven largely by drug acquisition and administration costs, and incremental QALY gain largely by differences in delayed EDSS progression. Cladribine tablets had a 93% probability of being cost-effective at a threshold of GBP 30,000 per QALY gained, and remained dominant across the scenario analyses tested. The greatest influence on results was the treatment effect on disability progression derived from the ITC.

Limitations: Uncertainty over the efficacy of DMT beyond trial durations. In line with other comparative effectiveness analyses, the network meta-analysis informing this cost-effectiveness analysis was associated with a degree of uncertainty. No treatment switching analyses were undertaken.

Conclusions: Cladribine tablets are a cost-effective alternative to alemtuzumab and natalizumab in the treatment of HDA-RRMS from the perspective of the NHS in England.

Keywords:

• Cladribine tablets
• alemtuzumab
• natalizumab
• multiple sclerosis
• cost-effectiveness

Transparency

Declaration of funding

This study was funded by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.

Declaration of financial and other relationships

RH was an employee of PAREXEL International, who acted as a paid health technology consultant to EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany. GH and SLW are employees of EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany. No authors received payment for the development of this manuscript. Peer reviewers on this manuscript have received an honorarium from JME for their review work. One reviewer discloses that they were an investigator on the CLARITY and CLARITY extension studies that were used for this cost-effectiveness analysis and, as a member of the steering committee for the trial, they were paid as a consultant by Merck-Serono. The remaining reviewers have no relevant financial relationships to disclose.

Acknowledgments

Editorial assistance was provided by Jo Whelan (Textpharm Ltd., Oxford, UK) funded by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.