Original Title: Fullstendig metodevurdering av legemidler ved multippel sklerose

Authors' objectives: The aim of this project was to compare the effect and cost-effectiveness of the disease modifying medicines used for multiple sclerosis in Norway.

Authors' results and conclusions: The key results are: • We identified 37 randomised clinical trials. The quality of the available evidence ranged from very low to high. • Alemtuzumab 12 mg had the best effect on annual relapse (for medicines we had evidence of high quality). Dimethyl fumarate 240 mg twice daily and fingolimod oral 0.5 mg were the most effective against disability progression (for medicines we had evidence of high quality). • Our results indicated that interferon beta-1a 44 mcg and peg-interferon beta-1a were associated with more withdrawal due to adverse events than placebo. The examined treatments had no effect on mortality compared to placebo. • Our health economic analysis, examining all multiple sclerosis treatment alternatives, indicated that alemtuzumab was more effective (in terms of quality-adjusted life-years (QALY)) and less costly than the other treatment alternatives. We did several scenario analyses and the cost-effectiveness results were robust to variations in the model assumptions. • The results of a scenario analysis that excluded alemtuzumab (the dominant strategy), showed that three treatments alternatives (interferon beta-1b (Extavia), peg-interferon beta-1a and natalizumab) could be cost-effective depending on the willingness-to-pay (WTP) per QALY. Assuming a WTP below NOK 1,000,000, interferon beta-1b (Extavia) was 40% likely to be the most cost-effective treatment, followed by peg-interferon beta-1a (30% likely). • The results of our model analysis showed that there is some degree of uncertainty regarding the input parameters. More research on efficacy and epidemiological data would have the greatest impact on reducing decision uncertainty. • Our budget impact analysis based on the results of our cost-effectiveness analysis, the drugs’ adverse events profile, and current clinical practice showed that there is a substantial potential for cost saving. CONCLUSION: Alemtuzumab 12 mg had the best effect against annual relapse. Dimethyl fumarate 240 mg twice daily and fingolimod oral 0.5 mg were the most effective against disability progression. Results indicate that some treatments are associated with more withdrawals due to adverse events than placebo. Our results showed that the examined treatments had no effect on mortality. Our health economic analysis indicated that alemtuzumab was more effective and less costly than the other treatment alternatives. A scenario analysis that excluded alemtuzumab indicated that three treatment alternatives (interferon beta-1b (Extavia), peg-interferon beta-1a and natalizumab) could be cost-effective depending on the WTP. For a WTP below NOK 1,000,000 per QALY, interferon beta-1b (Extavia) was approximately 40% likely to be the most cost-effective treatment, followed by peg-interferon beta-1a (approximately 30% likely). The results of probabilistic analysis showed that there is some degree of uncertainty regarding the input parameters. More research on efficacy and epidemiologic input parameters would have the greatest impact on reducing decision uncertainty. Our budget impact analysis showed that there is a substantial potential for cost saving.

Authors' methods: We conducted a systematic review based on the following conditions: Evidence should come from randomised controlled trials (RCTs) with study populations that included men and women aged 18 years or older were eligible. Modifying medicines used for multiple sclerosis were our intervention of interest (dimethyl fumarate, teriflunomide, interferon beta, peg-interferon, glatiramer acetate, natalizumab, fingolimod, and alemtuzumab). We included studies that compared these medicines to placebo or to each other. We examined the following endpoints: annual relapse, disability progression, mortality, serious adverse events, withdrawal from the study due to adverse events, hospitalisations, and health related quality of life. We systematically searched the literature for previously published health technology assessment reports or systematic reviews that answered our objectives, and met our inclusion criteria. We conducted a systematic review of randomised controlled trials to supplement the evidence of previously published health technology assessments. Two persons independently examined the risk of bias of included studies using the Norwegian Knowledge Centre for the Health Services methods. These are based on Cochrane methodology. We summarised the evidence from the randomised clinical trials quantitavely through network meta-analyses of data on direct and indirect evidence on all relevant comparisons. Two persons independently assessed the quality of the evidence for each selected endpoint. We used GRADE (Grading of recommendations Assessment, Development, and Evaluation) to assess our confidence in the effect estimates. In order to assess the cost-effectiveness of disease-modifying therapies in patients diagnosed with relapsing-remitting multiple sclerosis, we developed a decision analytic model. The economic model was developed in the form of a cost-utility analysis and included treatments approved and available in Norway. The model structure and all assumptions were adapted to the Norwegian setting based on Norwegian clinical practice. Efficacy estimates were taken from our network meta-analyses. Transitional probabilities were derived from published sources and clinical experts’ opinions. Quality of life data were extracted from published studies based on a systematic review of the literature. The costs of medications were based on prices obtained through the Drug procurement co-operation (LIS), and other costs were based on official Norwegian unit prices. We performed probabilistic sensitivity analyses, designed as a Monte Carlo simulation with 10,000 iterations, to explore the uncertainty surrounding our results.

Project Status: Completed

Year Published: 2016

URL for published report: https://www.fhi.no/en/publ/2016/legemidler-ved-multippel-sklerose/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Pubmed ID: 29553658

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo