Low fT3/fT4 Ratio Associates With Primary Nonresponse to Infliximab or Adalimumab

Lower baseline serum fT3/fT4 ratio was linked to female sex, higher inflammatory burden at baseline, baseline corticosteroid use, and predicted PNR to anti-TNF therapy at week 14, but not nonremission or change in fecal calprotectin concentrations at week 54.

Primary nonresponse (PNR) to infliximab or adalimumab at week 14 was associated with low baseline free triiodothyronine-to-thyroxine (fT3/fT4) ratio, according to study findings published in Alimentary Pharmacology & Therapeutics.

Data for this study were sourced from the Personalized Anti-TNF Therapy in Crohn’s Disease study (PANTS), which was conducted in the United Kingdom between 2013 and 2016. Predictors for PNR at week 14 and nonremission at week 54 were evaluated. Primary nonresponse was defined as exit prior to week 14 due to treatment failure, corticosteroid use, C-reactive protein (CRP) less than or equal to 3 mg/L or 50% from baseline, and Harvey Bradshaw Index (HBI) of less than or equal to 4 or a decrease of 3 points.

The study population comprised 997 individuals with a median age of 36.32 years, 52.86% were women, 93.78% were White, CRP was 7.00 mg/L, and HBI score was 5.00. Patients received infliximab (n=549) or adalimumab (n=448).

Baseline fT3/fT4 ratio differed significantly on the basis of sex (P <.001) and corticosteroid use at baseline (P <.001), in which the levels were lower for women and corticosteroid users compared with men and nonusers, respectively. In addition, fT3/fT4 ratio was correlated with age (r, -0.12; P <.001), disease duration (r, 0.06; P =.046), BMI (r, 0.12; P <.001), CRP (r, -0.10; P =.002), and fecal calprotectin (r, -0.12; P =.001).

Overall, serum fT3/fT4 ratio to predict PNR lacked diagnostic accuracy and is unlikely to be a clinically useful predictor.

At week 14, 25.5% had PNR, 13.6% had a response, and 39.8% were in remission. Stratified by treatment, 22.7% of infliximab recipients and 29.0% of adalimumab recipients had PNR. At week 54, 65.1% were not in remission.

Lower fT3/fT4 ratio was associated with PNR at week 14 (P <.001).

The optimal cutoff for baseline fT3/fT4 ratio was 0.31 with an area under the curve of 0.57, sensitivity of 0.62, and specificity of 0.53 for predicting PNR at week 14.

As steroid use was correlated with fT3/fT4 ratio, the investigators performed a sensitivity analysis excluding patients with steroid use. In this analysis, fT3/fT4 ratio was not associated with PNR at week 14. Similarly, no association was observed in a sensitivity analysis among patients aged 60 years or over.

The major limitation of this study was not using endoscopic markers of treatment failure.

“Lower baseline serum fT3/fT4 ratio was associated with female sex, higher inflammatory burden at baseline, and corticosteroid use and predicted PNR to anti-TNF treatment at week 14, but not non-remission, or changes in faecal calprotectin concentrations at week 54,” the study authors wrote. “Overall, serum fT3/fT4 ratio to predict PNR lacked diagnostic accuracy and is unlikely to be a clinically useful predictor.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Lin S, Chanchlani N, Carbery I, et al. Understanding anti-TNF treatment failure: does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease? Aliment Pharmacol Ther. 2022;56(5):783-793. doi:10.1111/apt.17089