Immunomodulator withdrawal not linked to loss of response in IBD

Among inflammatory bowel disease (IBD) patients, the discontinuation of immunomodulator treatment does not contribute to the risk of loss of response although it may lead to an increase in antidrug antibodies, according to a study.

Researchers looked at the medical records of 543 adult IBD patients who were on antitumour necrosis factor (anti-TNF) for at least 4 months plus an immunomodulator at baseline. The primary endpoints were loss of response (defined as anti-TNF discontinuation because of disease activity) and antibodies to anti-TNF. Secondary outcomes included anti-TNF dose escalations, anti-TNF discontinuation, and anti-TNF trough levels.

The analysis included 614 treatment episodes of combination therapy over 1,664 patient-years of follow-up. The immunomodulator was stopped in 296 (48.2 percent) episodes after a median of 0.9 years. Patients who discontinued vs continued the immunomodulator were more likely to have a higher body mass index, be anti-TNF naïve, and have longer follow-up (until anti-TNF discontinuation or censoring).

At the time of immunomodulator withdrawal, most patients (85 percent) were in clinical remission. The most common reason for treatment withdrawal was to de-escalate therapy. The median follow-up after immunomodulator withdrawal was 1.7 years.

Mixed-effects Cox regression analysis revealed no association between immunomodulator withdrawal and the risk of loss of response (adjusted hazard ratio [aHR], 1.08, 95 percent confidence interval [CI], 0.72–1.61). However, treatment withdrawal was linked to the frequent detection of antidrug antibodies (aHR, 2.14, 95 percent CI, 1.17–3.94) compared with continuation.

Clinical remission at the time of withdrawal was protective against the risk of loss of response (aHR, 0.48, 95 percent CI, 0.25–0.93), while longer duration of combination therapy before withdrawal the was linked to a lower risk of antidrug antibodies (HR, 0.56 per year, 95 percent CI, 0.32–0.91).

Finally, elevated infliximab trough levels prior to withdrawal lowered the subsequent risks of antidrug antibodies and loss of response. Infliximab trough levels were lower after immunomodulator withdrawal (p=0.01).

The present data suggest that objectifying remission and therapeutic drug monitoring prior to immunomodulator withdrawal may minimize the risk of loss of response.