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Meta-Analysis
. 2024 Jan 27;18(1):134-143.
doi: 10.1093/ecco-jcc/jjad118.

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies

Sebastiaan Ten Bokkel Huinink  1 , Doranne Thomassen  2 , Ewout W Steyerberg  2   3 , Renske W M Pauwels  1 , Maria J Casanova  4 , Guillaume Bouguen  5 , Joyce W Y Mak  6 , Tamas Molnár  7 , Alan J Lobo  8 , Jacob B Seidelin  9 , Aurelien Amiot  10 , Geert D'Haens  11 , Pauline Rivière  12 , Luisa Guidi  13 , Renata Bor  7 , Wei-Chen Lin  14 , Laurent Peyrin-Biroulet  15 , Javier P Gisbert  4 , C Janneke van der Woude  1 , Annemarie C de Vries  1
Affiliations
Meta-Analysis

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies

Sebastiaan Ten Bokkel Huinink et al. J Crohns Colitis. .

Abstract

Background: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.

Methods: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.

Results: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.

Conclusions: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

Keywords: Crohn’s disease; anti-TNF therapy; discontinuation; perianal fistulizing disease.

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Conflict of interest statement

STBH, DT, ES, RWMP, JM, AL, RB, WL none. CW received grant support from Falk Benelux and Pfizer; received speaker fees from AbbVie, Takeda, Ferring, Dr. Falk Pharma, Hospira, and Pfizer; and served as a consultant for AbbVie, MSD, Takeda, Celgene, Mundipharma, and Janssen. MJ has received education funding from Pfizer, Takeda, Janssen, MSD, Ferring, Abbvie, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, and Norgine. GB has received lecture fees from Abbvie, Ferring, MSD, Takeda, and Pfizer, and consultant fees from Takeda and Janssen. TM has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, and Teva. JS has served as national coordinator on studies from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, and Roche/Genentech, and received an unrestricted research grant from Takeda. AA has received consulting fees from Abbvie, Hospira, Takeda, Gilead, and Biocodex as well as lecture fees and travel accommodations from Abbvie, Janssen, Biocodex, Hospira, Ferring, Takeda, and MSD. AA also received advisory board fees from Gilead, Takeda, and AbbvieX. GDH has served as advisor for Abbvie, Ablynx, Alimentiv, Amgen, AM Pharma, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Immunic, Johnson and Johnson, Lamepro, Lument, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer, Polpharm, Prometheus laboratories/Nestle, Procise diagnostics, Protagonist, Salix, Samsung Bioepis, Sandoz, Setpoint, Shire, Takeda, Tigenix, Tillotts, Topivert, Versant, and Vifor; and received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Takeda, Tillotts, and Vifor. PR has received consultancy fees from Abbvie, Amgen, and Janssen. LG has received consultancies and/or speaker fees from AbbVie, Janssen, MSD, Mundipharma, Takeda, Vifor Pharma, and Zambon. LPB has received grant support, consulting fees, lecture fees, and advisory board fees from AbbVie, Takeda, and MSD, consulting fees, lecture fees, and advisory board fees from Janssen, Ferring, Tillots, Celltrion, Pfizer, and Roche, consulting fees and advisory board fees from Genentech, Pharmacosmos, Sandoz, Celgene, Allergan, Arena, Gilead, and Amgen, consulting fees from Boehringer Ingelheim, Index Pharmaceuticals, and Alma, consulting fees and lecture fees from Biogen and Samsung Bioepis, advisory board fees from Sterna, Nestle, and Enterome, lecture fees from Hikma, and holding stock options in CT-SCOUT. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma. AV has participated in advisory board and/or received financial compensation from the following companies: Janssen, Takeda, Abbvie, and Tramedico.

Figures

Figure 1.
Figure 1.
Cumulative probability of relapse after discontinuation of anti-TNF therapy in perianal fistulizing CD patients [all cohorts pooled].
Figure 2.
Figure 2.
Stratified meta-analysis of relapse rates at 1 year [a] and 2 years [b] after cessation of anti-TNF therapy.
Figure 3.
Figure 3.
Cumulative probability of relapse after discontinuation of anti-TNF therapy in perianal fistulizing CD patients split by relapse type.
Figure 4.
Figure 4.
Forest plot of the predictors and their hazard ratios [HRs] for relapse resulting from univariable [a] and multivariable [b] stratified Cox-regression analysis of all included cohorts [n = 311].
Figure 5.
Figure 5.
[a] Forest plot of fistula characteristics and their hazard ratios [HRs] for relapse in all cohorts where fistula characteristics were recorded [n = 166]. [b] Forest plot of fistula characteristics and their hazard ratios [HRs] for relapse in all cohorts where fistula characteristics were recorded, in the subgroup of patients with perianal fistulizing disease and in luminal remission at the time of start anti-TNF therapy [n = 144].
See this image and copyright information in PMC

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