Relapse after withdrawal from anti‐TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta‐analysis

Abstract

SummaryBackgroundInfliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti‐TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation.AimTo establish outcomes following anti‐TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta‐analysis.MethodsA retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti‐TNF for sustained remission. Meta‐analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC).ResultsRelapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109/L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta‐analysis, estimated 1‐year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti‐TNF was successful in 88% for CD and 76% UC/IBDU.ConclusionsAssimilation of all available data reveals remarkable homogeneity. Approximately one‐third of patients with IBD flare within 12 months of withdrawal of anti‐TNF therapy for sustained remission.

De‐escalating medical therapy in Crohn’s disease patients who are in deep remission: A RAND appropriateness panel

“…Importantly, panellists agreed that there is no scenario in which stopping monotherapy is considered appropriate. Studies of patients withdrawing from anti‐TNF monotherapy demonstrate that up to two‐thirds of patients relapse after only 12 months . Among those withdrawing from azathioprine, relapse risk remains high regardless of the duration of prior treatment and increases over time, but outcomes may vary based on extent of disease, gender and age .…”

“…Relapse rates among those who discontinue the IM after combination therapy are slightly higher at 55%‐60%, and those who discontinue IM monotherapy show relapse rates at 2 years up to 70% . These studies showed that re‐treatment with the same agent is successful in achieving remission in most, but not all, patients …”

“…Although de-escalation studies exist, the extrapolation and application of such data to common and complex clinical scenarios that reflect the spectrum of age, gender, therapies tried and severity of CD encountered by clinicians remains elusive. De-escalation studies to date have evaluated outcomes in patients treated with anti-TNF therapy in combination with IM therapy who discontinue the anti-TNF or IM, [1][2][3][4][5][6][7] as well as in patients on anti-TNF or IM monotherapy who are withdrawn from therapy. 2,[8][9][10][11][12][13] Metaanalyses of de-escalation strategies demonstrate a relapse rate of approximately 50% at 2 years in patients treated with combination therapy who discontinued the anti-TNF, 1-3 and a similar rate is seen in those who discontinue anti-TNF monotherapy.…”

“…1 These studies showed that re-treatment with the same agent is successful in achieving remission in most, but not all, patients. [1][2][3] Extrapolating from these data, clinical and biochemical factors associated with the risk of relapse have been identified, 1,[14][15][16] and algorithms for de-escalation have been proposed. 17 However, prospective trials of anti-TNF/IM withdrawal in patients on combination therapy are still ongoing, 18,19 and prospective trials of IM monotherapy withdrawal to date have assessed only thiopurines, [10][11][12][13] potentially limiting applicability of study results to real-world clinical practice where both thiopurines and methotrexate are used.…”

The impact of updated NICE guidelines on biologic treatment of ulcerative colitis: reflections on past practices, the changing present and implications for the future

“…Indeed, a retrospective UK-wide study explored the outcome of anti-TNF withdrawal in inflammatory bowel disease and found that 35% of UC patients had relapsed within a year of cessation. [15] In addition, treatment withdrawal may not be the preferred option for many patients [16] or clinicians.…”