Stopping Anti-tumour Necrosis Factor Therapy in Patients With Perianal Crohn's Disease

Joyce Wing Yan Mak; Whitney Tang; Terry Cheuk Fung Yip; Zhi Hua Ran; Shu Chen Wei; Vineet Ahuja; Sudheer Kumar; Wai Keung Leung; Ida Hilmi; Julajak Limsrivilai; Satimai Aniwan; Belsy C. Y. Lam; Kam Hon Chan; Ka Man Ng; Chi Man Leung; Michael K. K. Li; Fu Hang Lo; Alex Shun Fung Sze; Steven Woon Choy Tsang; Aric J. Hui; Juanda Leo Hartono; Siew C. Ng


Aliment Pharmacol Ther. 2019;50(11):1195-1203. 

In This Article

Abstract and Introduction


Background: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy.

Aim: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy.

Methods: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method.

Results: After a median follow-up of 89 months (interquartile range [IQR]: 65–173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01–1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58–2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months.

Conclusions: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.


Perianal Crohn's disease (CD) affects one-third of patients with CD. It represents a distinct, aggressive and disabling phenotype of CD. Over 40% CD patients presented with perianal disease at diagnosis.[1] The presence of perianal CD at presentation is associated with an increased number of hospital admissions, increased surgical resections in the subsequent 5 years and predisposed patients to chronic disabling symptoms.[2]

Approximately one-third of perianal CD patients responded to anti-tumour necrosis factor (anti-TNF) therapy.[3,4] A recent systemic review and meta-analysis of 24 studies by Yassin et al revealed that combined medical and surgical management led to higher complete remission rate compared with monotherapy (52% vs 43%).[5] Overall, long-term infliximab therapy with combined medical and surgical management produced clinical remission with closure of fistula openings in 36%-58% of patients with perianal CD.[6] Previous studies using MRI to monitor treatment response to anti-TNF therapy revealed that radiological healing of perianal Crohn's fistula lagged behind clinical remission by a median of 12 months and that long-term maintenance therapy is probably required to prevent recurrence despite a clinically healed external opening.[7,8]

The pivotal STORI trial (Infliximab diSconTinuation in Crohn's disease patients in stable Remission on combined therapy with Immunosuppressors) showed that around half of the CD patients who were treated for at least 1 year with infliximab and thiopurine experienced a relapse within 1 year after stopping infliximab.[9] In the long-term follow-up of the STORI cohort, 21% of patients did not require restart of infliximab or other biologic after 7 years of stopping infliximab and 30.1% experienced treatment failure at 6 years amongst those who required restarting of infliximab.[10] However, few studies have specifically assessed risks of relapse of perianal CD after discontinuation of biologics. It was reported that PCD patients had early relapse after stopping infliximab. Two-thirds of perianal CD patients relapsed within 1 year after stopping infliximab.[11] Long-term infliximab treatment was associated with better outcomes in patients with perianal CD.[12] A recent study demonstrated that half of the Caucasian perianal CD patients developed relapse within 5 years after stopping anti-TNF therapy while continued use of immunosuppressants might decrease the risk of relapse (hazard ratio, HR = 0.3). Retreatment with anti-TNF led to clinical remission in 96% of patients.[13] The aim of this study was to assess the risk of relapse after stopping anti-TNF in patients with perianal CD in the Asian population and their outcomes after stopping anti-TNF.