Lancet Gastroenterol Hepatol

Sustained anti-TNF treatment response uncommon in Crohn’s disease

April 24, 2024

In the Personalized Anti-TNF therapy in Crohn’s disease (PANTS) UK cohort study, investigators found that only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predicted loss of response by year 3 of treatment, suggesting that higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes.

• 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab entered the PANTS-extension study (median age 32.5 years, 51% female). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40.2%, 34.4%, and 34.7%, and for adalimumab 35.9%, 32.9%, and 28.9%, respectively.
• Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6.1-10.0 mg/L for infliximab and 10.1-12.0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34.4%, 54.5%, and 60.0%, and for adalimumab 32.1%, 47.2%, and 68.4%, respectively.
• Loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14. For patients treated with infliximab, loss of response was also associated with female sex, obesity, baseline white cell count, and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response.
• By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44.0% among patients treated with infliximab and 20.3% among those treated with adalimumab.

Source:

Chanchlani N; PANTS Consortium; et al. (2024, April 16). Lancet Gastroenterol Hepatol. Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study. https://pubmed.ncbi.nlm.nih.gov/38640937/