Paediatric inflammatory bowel disease (IBD) patients who have achieved clinical remission during tumour necrosis factor inhibitor (anti-TNF) therapy are likely to flare if they stop treatment, researchers from the IBD Porto Group of ESPGHAN has found.
In a retrospective multicentre cohort, relapse occurred in 54 percent of patients within 12 months of stopping anti-TNF. By 24 months, the percentage of patients who had relapsed climbed to 76 percent. [ESPGHAN 2026, abstract OP064]
“The median time to relapse was 9 months, indicating that most flares happened within the first year,” reported lead researcher Dr Maya Granot from Tel-Aviv University, Tel Aviv, Israel.
Biologic treatment was re-initiated in 35 percent of patients within 12 months and in 69 percent by 24 months. The median time to a new biologic treatment was 11 months.
Kaplan-Meier analyses of survival without flare and survival without needing a biologic showed a steady and steep decline following anti-TNF withdrawal, Granot noted.
Rates of relapse and biologic re-initiation did not significantly differ between the ulcerative colitis (UC) and the Crohn’s disease (CD) subgroups (p>0.05 for all), “suggesting that once a biologic is withdrawn, the disease course is broadly similar,” she added.
Less tolerant to withdrawal
The relapse rates in this paediatric cohort are substantially higher than what is reported in adult cohorts (around one-third at 12 months and one-half at 3–5 years), even in carefully selected patients, according to Granot.
“This may reflect inherent differences in paediatric IBD biology and suggests that paediatric disease is less tolerant to withdrawal,” she said.
Additional analyses showed that even being in deep remission provided no protection against relapse after anti-TNF withdrawal. The respective relapse rates at 12 and 24 months were 54 percent and 78 percent among those in biochemical remission* and 42 percent and 68 percent among those in endoscopic remission**.
“Relapse rates remained very high despite most patients meeting the STRIDE-II treat-to-target standards. Neither biochemical nor endoscopic remission significantly predicted sustained remission off therapy,” Granot said.
The discontinuation dilemma
TNF inhibitors have remarkably improved outcomes in paediatric IBD and are now a cornerstone in the treatment of moderate-to-severe disease. But concerns about cumulative adverse effects, treatment burden, and rising healthcare costs with prolonged exposure prompt families to request withdrawal once sustained remission is achieved.
To explore potential candidates for safe anti-TNF withdrawal, Granot and colleagues performed Cox proportional hazards regression. They tested every routinely available clinical and biological variable: sex, age, disease duration, IBD subtype, disease location and behaviour, biochemical markers, endoscopic remission, anti-TNF type and line of therapy, through levels, antidrug antibodies, and concomitant immunomodulators (including 5-ASA).
None of the variables reliably identified who would stay in remission off anti-TNF.
“So, even if a child appeared in perfect remission—with labs normalized, mucosa healed, and no symptoms—three out of four will relapse within 2 years of stopping anti-TNF,” Granot pointed out.
De-intensification as alternative
Rather than complete discontinuation of anti-TNF therapy, clinicians may consider a stepwise de-escalation as an alternative approach, she said.
For example, adalimumab dosing could be extended to every 3 weeks, as described in a research report. [J Pediatr Gastroenterol Nutr 2025;80:998-1001]
This strategy, according to Granot, may mitigate flare risk while reducing drug exposure. “This matters greatly in children with IBD, for whom relapse during childhood can jeopardize growth, puberty, bone health, school attendance, and psychosocial functioning.
“Until we have a better biomarker for risk stratification, our clinical guidance is to approach anti-TNF withdrawal with caution,” she said. “Always use shared decision-making so families understand the real risk, consider de-intensification as an alternative, and monitor closely if withdrawal is attempted.”
In the current study, only 83 children with IBD stopped anti-TNF treatment over 7 years across 21 expert centres in Europe and Asia. “This is remarkably low, and it tells us that experienced clinicians are already cautious about withdrawal in this population.”
Study details
The 83 children with paediatric-onset CD (n=59) or UC (n=24) included in the study had a median age at diagnosis of 11.6 years. They had been in remission for at least 6 months during anti-TNF therapy, which was infliximab in 80 percent and adalimumab in 20 percent.
The median age at anti-TNF discontinuation was 14.8 years. Anti-TNF was used as first-line biologic in 88 percent of patients. At treatment withdrawal, 93 percent of patients were in biochemical remission, and 68 percent were in endoscopic remission.
Reasons for withdrawal included patient/parent preference (40 percent), adverse events (30 percent), physician decision (25 percent), and cost (5 percent).
Among patients who relapsed and needed treatment, 57 percent of those who received infliximab and 27 percent of those who received adalimumab restarted their original anti-TNF agent. Others switched to either infliximab or adalimumab or a different biologic such as vedolizumab, ustekinumab, and risankizumab.
The primary outcome of relapse was defined a clinical plus biochemical or endoscopic activity leading to hospitalization, steroid use, or initiation of new biologic.