Efficacy, safety, and cost-effectiveness of therapeutic drug monitoring (TDM) for TNF inhibitor therapy in rheumatic disease: A systematic review and meta-analysis

Wenliang Dong; Xiaowen Hu; Caiying Wu; Gengchen Wang; Yi Fang; Luwen Shi; Xiaoyan Nie

doi:10.1016/j.semarthrit.2023.152302

Efficacy, safety, and cost-effectiveness of therapeutic drug monitoring (TDM) for TNF inhibitor therapy in rheumatic disease: A systematic review and meta-analysis

Semin Arthritis Rheum. 2023 Dec:63:152302. doi: 10.1016/j.semarthrit.2023.152302. Epub 2023 Nov 4.

Authors

Wenliang Dong¹, Xiaowen Hu², Caiying Wu², Gengchen Wang², Yi Fang³, Luwen Shi⁴, Xiaoyan Nie⁵

Affiliations

¹ Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Clinical Trial Institution, Peking University People's Hospital, Beijing 101109, China.
² Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
³ Clinical Trial Institution, Peking University People's Hospital, Beijing 101109, China. Electronic address: phaseistudy@163.com.
⁴ Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; International Research Center for Medicinal Administration, Peking University, Beijing 100191, China. Electronic address: shilu@bjmu.edu.cn.
⁵ Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; International Research Center for Medicinal Administration, Peking University, Beijing 100191, China. Electronic address: niexy@pku.edu.cn.

PMID: 37951128
DOI: 10.1016/j.semarthrit.2023.152302

Abstract

Objective: The benefits of TDM-guided TNFi therapy in patients with rheumatic disease was still controversial. This systematic review and meta-analysis was conducted to explore if the TDM-guided TNFi therapy is superior to empirical-guided therapy.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956).

Results: A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I²=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I²=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I²=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I²=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I²=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost.

Conclusion: TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.

Keywords: Dose reduction; Response; Rheumatic disease; Therapeutic drug monitoring; Tumor necrosis factor inhibitors.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Cost-Benefit Analysis
Drug Monitoring
Humans
Recurrence
Rheumatic Diseases* / drug therapy
Tumor Necrosis Factor Inhibitors* / adverse effects
Tumor Necrosis Factor Inhibitors* / therapeutic use

Substances

Tumor Necrosis Factor Inhibitors