Supratherapeutic Infliximab Levels Do Not Predict Risk of Short-term Complications in Adults With Crohn’s Disease

Abstract

Background: It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/ NIC). We aimed to assess the risk of IC and NIC in patients with different TLs. Methods:We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥ 15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC.Results: Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups (P = 0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab > 40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio = 0.51, P = 0.04), but not NIC (adjusted odds ratio = 0.72, P = 0.46). Conclusions:In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.

Letter: immunogenicity is not the root cause for loss of response to anti‐TNF agents in patients with IBD in TDM era

“…[2][3][4] On top, more evidence is emerging on the benefits of therapeutic drug monitoring (TDM) and dose escalation in mitigating immunogenicity and subtherapeutic trough levels to recapture response, 5,6 and the safety of aiming for higher serum levels. 7 Most patients who lost response in our cohort (n = 95, 72.5%) had trough levels within the therapeutic range and absent anti-drug antibodies (ie, mechanistic or pharmacodynamic LOR) (Figure 1B).…”

Increased Risk of Infection With High Infliximab Trough Level

“…We read with great interest the article by Bhattacharya et al,1 assessing the risk of infectious complications (IC) and noninfectious complications (NIC) in patients with Crohn’s disease (CD) receiving infliximab with therapeutic drug monitoring. The authors reported no association between the infliximab trough levels (TL) and risk of short-term IC or NIC but a higher rate of IC with a shorter duration of exposure.…”