Introduction
Proactive therapeutic drug monitoring (TDM) has been suggested to improve outcomes in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNFα) therapy. A systematic review and a meta-analysis of the literature was conducted to assess treatment efficacy and safety, and a systematic review to compare the cost-effectiveness of proactive TDM versus conventional management during maintenance treatment with anti-TNFα.
Aims & Methods
A search was conducted of MEDLINE, EMBASE, and the Cochrane Library up to January 2022. The primary outcome was the ability to maintain clinical remission at 12 months. The certainty of evidence was determined using the GRADE approach.
Results
Nine studies were identified: one systematic review, six randomised clinical trials, and two cohort studies (for safety evaluation). The analysis of the clinical trials showed no superior efficacy of proactive TDM [relative risk 1.16; 95% confidence interval (CI): 0.98–1.37, n=528; I2=55%]. In contrast, the analysis of the cohort studies and systematic review revealed that proactive TDM could improve the durability of anti-TNFα treatment [odds ratio (OR) 0.12; 95%CI: 0.05–0.27; n=390; I2=45%), prevent acute infusion reactions (OR 0.21; 95%CI: 0.05–0.82; n=390; I2=0%), decrease adverse events (OR 0.38; 95%CI: 0.15–0.98; n=390; I2=14%), and reduce the probability of surgery, at lower economical expenditure.
Conclusion
The analysed evidence did not confirm the superiority of proactive TDM of anti-TNFα agents over conventional management. Therefore, proactive TDM should not be recommended for the management of IBD patients receiving maintenance anti-TNFα treatment.
References
1. Vande Casteele N, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-1329.
2. D’Haens G, et al. Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, and Corticosteroid-Free Remission in Patients With Active Luminal Crohn’s Disease. Gastroenterology. 2018;154(5):1343-1351.
3. Assa A, et al. Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children With Crohn’s Disease Compared With Reactive Monitoring. Gastroenterology. 2019;157(4):985-996.
4. Syversen SW, 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(23):2375-84.
5. Strik AS, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021;56(2):145-54.
06. D’Haens GR, et al. Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results. Gastroenterology. 2022;162(7):1876-90.
07. Papamichael K, et al. Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2017;15(10):1580-1588.e3.
Disclosure
B Novella Arribas, F Rodríguez Salvanés, and P Loeches Belinchón have no conflict of interest. N Manceñido Marcos has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie, Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and Tillots Pharma. G Mora Navarro has served as a speaker and consultant for or has received research and training funding from Sanofi, Lilly, ESTEVE, and AstraZeneca. JP Gisbert has served as a speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Sandoz, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma.