Real world Crohn’s study reveals predictors of response to TNFi

IBD

By Michael Woodhead

3 Jun 2018

Long term outcomes for TNF inhibitors in people with Crohn’s disease are predicted by initial response, BMI and drug levels, a major UK study has shown.

People with high BMI and those who had not shown a response within the first 14 weeks were less likely to be in remission at 12 months following treatment with infliximab or adalimumab, according to Dr Nick Kennedy, lead researcher of the PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) trial co-ordinated by the IBD Pharmacogenetics research group at University of Exeter, UK.

Presenting the findings at DDW 2018 here in Washington DC, Dr Kennedy said it was the largest real world prospective study of anti-TNF therapy (TNFi), involving more than 1600 patients with Crohn’s Disease from multiple centres across the UK.

The study showed that about 25% of Crohn’s patients treated with a TNFi experienced a primary non-response at week 12-14, with similar rates of remission (42%) seen with infliximab and adalimumab.

High BMI was a significant factor predicting poor response to all drugs at 14 weeks, and at one year. Likewise low drug concentrations were also associated with poor response at 14 weeks and one year.

The week 14 clinical status predicted outcomes at one year, when almost 40% of patients using the TNF drugs were in steroid-free remission.

“Notably, very few patients who were primary non-responders at week 14 eventually came into remission at the end of the year,” Dr Kennedy told the meeting.

Anti-drug antibody formation was common and was associated with non-remission at one year. Immunogenicity was attenuated among patients using immunomodulators, but was more common among patients with high BMI or were smokers. Genetic status (HLA-DQA1*05 haplotype) was also a factor in risk for developing immunogenicity.

In terms of safety, adverse events severe enough to lead to drug withdrawal were seen in around 8% of patients. The five deaths seen in the trial occurred due to sepsis in patients over 70 with all but one occurring in patients who were taking steroids, said Dr Kennedy.

The trial results showed there were opportunities early in therapy of Crohn’s disease to optimise the management of anti-TNF therapies and to prevent treatment failure, he concluded.

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