One unquestionable effect of proactive TDM is that the process of checking and controlling drug levels suggests for the treating physician better control over the anti-TNF therapy and for the patient reassurance that the treatment is in the intended target range. Proactive TDM also may be cost effective in the group of patients whose anti-TNF treatment regimen can be deescalated because of high drug levels. Despite the increased number of studies showing no clinical advantage of proactive TDM of every patient on anti-TNF therapy, there may be benefits for subgroups. Proactive TDM with point-of-care testing of drug levels may be helpful during induction therapy in patients with a high inflammatory burden, which results in uncontrolled drug loss via the intestine. Proactive TDM during maintenance therapy (for example, every 6-12 months) may be beneficial in subgroups of patients at risk for developing low anti-TNF levels or anti-drug antibodies, such as patients with a genetic predisposition to anti-TNF anti-drug antibody formation (such as the HLA-DQ1*05 allele), patients on a second anti-TNF therapy after loss of response to the first one, and patients on anti-TNF therapy in combination with thiopurines or methotrexate who deescalate to anti-TNF monotherapy.
In summary, there is no doubt that proactive TDM is better than no TDM (meaning no drug adjustments at all). However, nearly all controlled prospective studies show no significant benefit of proactive TDM versus reactive TDM or drug escalation based on clinical symptoms or biomarkers. Future studies should target clearly defined patient groups at risk of losing response to anti-TNF to clarify if proactive TDM is a valuable tool to achieving better therapeutic results in clinical practice.
Dr. Herfarth is professor of medicine and codirector of the UNC Multidisciplinary IBD Center at University of North Carolina at Chapel Hill. He reports serving as a consultant to Alivio Therapeutics, AMAG, Bristol Myers Squibb, Boehringer Ingleheim, ExeGi Pharma, Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, and Seres and receiving research support from Allakos, Artizan Biosciences, and Pfizer.
Relevant resources
- Syversen SW et al. JAMA. 2021;326:2375-84.
- Strik AS et al. Scand J Gastroenterol. 2021 Feb;56(2):145-54.
- Bossuyt P et al. J Crohns Colitis. 2022 Feb 23;16(2):199-206.
- D’Haens G et al. Gastroenterology. 2018;154:1343-51.e1.
