Background: TNF-inhibitors improve health-related quality of life (HRQoL) in patients with immune-mediated inflammatory diseases such as rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, psoriasis, Crohn’s disease and ulcerative colitis, but loss of response to therapy over time is a major concern. Sub-therapeutic drug levels and the development of neutralizing anti-drug antibodies are major contributors to loss of treatment response. Proactive therapeutic drug monitoring (pTDM) intends to optimise therapy using regular pharmacokinetic testing, allowing for individualised dose adjustments. This personalised treatment strategy has shown to improve patient health by reducing flares in patients on infliximab therapy [1].

However, the paucity of health economic data has been reported as a main reason why pTDM is currently not recommended in most treatment guidelines for immune-mediated inflammatory diseases. Based on data from the NOR-DRUM B trial [1], we intended to fill this evidence gap.

Objectives: To evaluate cost-effectiveness of pTDM of infliximab.

Methods: In the 52-week randomised, open-label, multicentre NOR-DRUM B trial [1], 454 adult patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, psoriasis, Crohn’s disease or ulcerative colitis on infliximab were randomly assigned to infliximab dosing based on TDM or standard infliximab therapy. For each of the 454 participants we estimated 12-month costs from a healthcare perspective, including pharmaceuticals, biochemical tests and other healthcare utilization. Unit costs (2024 Euros) were based on market prices, DRG cost weights and reimbursement tariffs. We captured health outcomes with the EQ-5D-3L as well as SF-6D. Since randomisation resulted in imbalanced treatment groups, we adjusted QALY calculations for difference at baseline, as recommended for health economic evaluations [2]. We estimated the incremental cost-effectiveness ratio (ICER), expressed as EUR per QALY, as an indicator of cost-effectiveness. The ICER was compared to the range of cost-effectiveness thresholds commonly used in Norway. We assessed the impact of sampling variability using the non-parametric bootstrap method. Results from the bootstrap were plotted on the cost-effectiveness plane and presented in a cost-effectiveness-acceptability curve [3]. The cost-effectiveness plane simultaneously shows the difference in costs and the difference in health gains between the comparator (origo) and the intervention, while the cost-effectiveness acceptability curve illustrates the probability that the intervention is cost-effective at varying threshold levels.

Results: The mean one-year costs per patient were €592 lower (95% CI: -1,304; 107)) for pTDM than for standard therapy (Table 1), due to less use of medications and other healthcare resources. Patients receiving pTDM had fewer flares (83 vs 124), leading to better health as measured by EQ-5D and SF-6D after adjusting for baseline imbalance and resulting in a QALY gain of 0.0018 (95% CI: -0.0126; 0.0165). The estimated ICER is illustrated by the dark dot on the cost-effectiveness plane in Figure 1. Most bootstrapped results (95%) indicate cost-savings, while 62% of the bootstrapped results indicate a positive health gain. At the proposed Norwegian threshold value of €23,755/QALY, pTDM has a probability of 95% of being a cost-effective alternative.

Conclusion: We found pTDM of infliximab to be a cost-effective treatment strategy compared to standard therapy. This analysis supports the use of pTDM of infliximab as recently suggested by a BMJ clinical guideline [4] and can inform future treatment recommendations regarding pTDM.

REFERENCES: [1] Syversen SW, Jørgensen KK, Goll GL, et al. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA 2021;326:2375–84.

[2] Manca A, Hawkins N, Sculpher MJ. Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance of controlling for baseline utility. Health Econ. 2005;14(5):487-96.

[3] Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, et al. Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report. Value Health. 2015;18(2):161-72.

[4] Kawano-Dourado L, Kristianslund EK, Zeraatkar D, Jani M, Makharia G, Hazlewood G, et al. Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline. Bmj. 2024;387:e079830.

Figure 1.

Cost-effectiveness plane and cost-effectiveness acceptability curve of pTDM vs standard therapy

Acknowledgements: NIL.

Disclosure of Interests: Teresa Holly: None declared, Marthe Kirkesæther Brun: None declared, Kristin Kaasen Jørgensen Janssen and Norgine, AstraZeneca, IPSEN, Orphalan, dr. Falk, IPSEN, Travel grants Advanz Pharma and CSL Vifor, Guro Løvik Goll: None declared, Joe Sexton: None declared, Johanna Elin Gehin: None declared, Tore K. Kvien: None declared, Jørgen Jahnsen AbbVie, Boerhinger Ingelheim, BMS, Celltrion, Giliad, Johnson&Johnson, Novartis, Pfizer, Roche, Takeda and Sandoz, AbbVie, Boerhinger Ingelheim, BMS, Celltrion, Giliad, Johnson&Johnson, Novartis, Pfizer, Roche, Takeda and Sandoz, AbbVie, Boerhinger Ingelheim, BMS, Celltrion, Giliad, Johnson&Johnson, Novartis, Pfizer, Roche, Takeda and Sandoz, Sella Aarrestad Provan: None declared, Nils Bolstad Roche, Napp, Sandoz, Pfizer, Janssen, Eline Aas: None declared, Espen A. Haavardsholm Novartis, AbbVie, Eli Lilly and Pfizer, Ivar Kristiansen: None declared, Silje Watterdal Syversen: None declared, Gunhild Hagen Pfizer 2015-2018.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.