Drug holidays from monoclonal antibodies may increase non-persistence in patients with Crohn’s disease and develop as soon as six months of pausing treatment, according to results of a large-scale study presented at AGW 2024.
Speaking in Adelaide on Sunday, Professor Rupert Leong said he would advise against drug holidays if given the choice, but if this was not possible, then therapeutic drug monitoring for loss of response and consideration of a concomitant immunomodulator to reduce immunogenicity might be of benefit.
His study on the effect of drug holidays on persistence was the first to evaluate comparative effectiveness encompassing all monoclonal antibody (mAB) classes.
The study involved 19,087 patients with Crohn’s disease on advanced therapy from the Persistence Australian National IBD Cohort (PANIC), representing almost 32,000 treatment lines and almost 80,000 patient years of follow up.
Researchers compared 28,584 treatment lines for controls against 3,383 lines of therapy for patients who took drug holidays (mean duration 414 days).
The drug holiday pause was defined as stopping prescribing for at least six months, with recommencement of the mAB after six months.
Findings revealed that drug holidays resulted in a 11% decrease in persistence. Median persistence was 41 months for controls, reducing to 23 months for drug holiday – equivalent to 18 months of reduction in the median persistence.
Drug holidays were more likely in younger women, especially around childbearing age; patients on TNF inhibitors; patients on monotherapy and bio-naive patients.
TNF inhibitors and ustekinumab were the most likely to be affected by drug holidays, most likely through immunogenicity for anti-cytokines, said Professor Leong, a gastroenterologist at Concord Repatriation General Hospital, Sydney.
He added that for vedolizumab, there was no significant decrease in persistence following drug holiday versus controls, with the mAB potentially more resistant to a stop-start strategy due to its high receptor saturation.
Data also showed loss of persistence was independent to the duration of the drug holiday, with no treatment lines meeting statistical significance.
Other results indicated that use of immunomodulators might reduce the loss of persistence for TNF inhibitors and ustekinumab, but not for vedolizumab.
“With ustekinumab, without immunomodulator, there was a significant divergence in persistence [and] with immunomodulator this significance was lost. This indicates using immunomodulators with ustekinumab can eliminate the loss of persistence with that drug holiday. That might be something that one can consider when taking a break from ustekinumab,” Professor Leong said.
The study also identified higher persistence in patients on vedolizumab or ustekinumab versus TNF inhibitors (HR 1.66 and 1.48 respectively), patients on immunomodulators (HR 1.11), males (HR 1.15) and those who had advanced therapy-naive status (HR 1.33), but not in patients on drug holiday (HR 0.72).
“Drug holiday was a significant predictor of decreased persistence and with propensity score matching, drug holiday continued to be a significant predictor of loss of persistence as an independent variable,” Professor Leong concluded.
He said the data could be used to counsel patients on the risks of drug holidays.