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Cost-Effectiveness Analysis of Parenteral Methotrexate for the Treatment of Crohn’s Disease

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Despite worldwide use of parenteral methotrexate (pMTX), health economic evidence for its use in Crohn’s disease (CD) is limited. The low price of this generic drug has removed any commercial incentive to further invest in research. However, there is an unmet need for treatment of mild-to-moderate CD, since biological/targeted therapies are usually reserved for patients with more severe disease due to the higher costs of these treatments.


To evaluate the cost-effectiveness of pMTX compared to the standard of care (SOC, i.e., high doses of oral corticosteroids (hdCS) followed by gradual tapering) for the treatment of mild-to-moderate CD in the Czech Republic.


We developed a 3-year Markov model with a 1-week cycle length comprising five health states. The model projected quality-adjusted life-years (QALYs) and costs from the healthcare payers’ perspective. Efficacy data were obtained from a systematic literature review of clinical trials and extrapolated using survival analysis.


Over a 3-year time-horizon, pMTX yields additional 0.111 QALYs (1.798 vs. 1.687) at an additional cost of €513 (€3087 vs. €2574), with an incremental deterministic (probabilistic) cost-effectiveness ratio of €4627 (€4742)/QALY, far below the willingness-to-pay (WTP) threshold (≈ €47,000/QALY). The probabilistic sensitivity analysis showed that the probability of pMTX being cost-effective was 100%. A one-way sensitivity and scenario analysis confirmed the robustness of the base-case result.


Parenteral MTX proved to be cost-effective in patients with mild-to-moderate CD. This is the first published cost-effectiveness analysis of pMTX for this indication. It also shows an example of a lack of valuation of generic therapy despite its cost-effectiveness and a clear benefit to the healthcare system.

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We thank Thomas O. Secrest for proofreading and Verka Horackova for graphical support. We also thank the reviewers for their insightful comments, which increased the quality of the manuscript. I thank my son Benjamin and loving wife Kveta for their unbelievable support (TM).

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Correspondence to Barbora Decker.

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Medac Czech Republic partly supported the preparation of the analysis for the purposes of obtaining reimbursement from public health insurance in the Czech Republic. However, the preparation of the publication was not financially supported.

Conflicts of interest

TM and BD are employees of Value Outcomes. Value Outcomes is a consultancy company working for the pharmaceutical industry in the field of market access, health economics, and outcomes research. TD is the director and owner of Value Outcomes.

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Availability of data and material

The authors confirm that the data supporting the findings of the analysis are publicly available within the article, its supplementary materials and the articles referenced in the manuscript.

Code availability

The cost-effectiveness model is available from the author TM upon request.

Author contributions

All authors contributed to the analysis conception, its design, and the material preparation and data collection. The analysis was performed by TM, clinical background was provided by BD, and collection of inputs was done by all authors. The manuscript was written by BD and TM, all authors commented on each version of the manuscript. All authors read and approved the final manuscript. TD supervised the process.

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Mlcoch, T., Decker, B. & Dolezal, T. Cost-Effectiveness Analysis of Parenteral Methotrexate for the Treatment of Crohn’s Disease. Appl Health Econ Health Policy 19, 593–604 (2021).

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