Introduction

Side effects, patient preference, and high costs may prompt cessation of anti-TNF therapy in ulcerative colitis (UC) patients in sustained remission. Given the risk of relapse, careful patient selection is essential. This study aimed to assess relapse rates and identify predictors of relapse following anti-TNF cessation in UC patients in remission.

Aims & Methods

A systematic search on cohort studies reporting relapse rates after cessation of anti-TNF therapy in ≥30 UC patients in clinical remission was performed 6 September 2024. Individual patient data was requested. We excluded patients with steroid use, ≤6 months anti-TNF therapy, ≤16 years, previous colectomy (n=4), golimumab as anti-TNF therapy (n=3) or without follow-up. Continuation of treatment with immunomodulators or mesalamine at cessation of anti-TNF was allowed. Relapse was defined as the need to (re)start treatment with steroids, anti-TNF or other advanced therapies, or the need for surgical treatment, as applied by the original author. Pooled relapse rates were computed using a random-effects model. A prediction model was built with a Cox proportional hazards model, performance assessed by iteratively leaving one study out (internal-external cross-validation, IECV). Missing covariate data were multiply imputed 100 times using the MICE algorithm. Variable selection was guided by three criteria: ≤20% missing data, a univariate p-value ≤ 0.2, and input from clinical experts.

Results

In total, 654 patients from 8 studies were included in the individual participant data meta-analysis. At anti-TNF cessation, median age was 40 years (IQR 31-51) with a median anti-TNF treatment of 18 months (IQR 18-36). The majority of patients were treated with infliximab (n = 610, 93%). Only 42 patients (9%) received a second-line anti-TNF therapy. The pooled relapse rate were 24% [95% CI 19-29%, I² = 44%] and 34% [95% CI 29-40%, I² = 39] at 1 and 2 years after cessation, respectively. Upon cessation, 211 patients (33%) continued mesalamine, 239 (39%) thiopurines, and 136 (22%) a combination of both. In our model, thiopurine therapy and older age at cessation were associated with a reduced risk of relapse, whereas immunomodulator refractoriness as an indication for starting anti-TNF therapy was associated with an increased risk. Other factors included in the prediction model were disease extent, type of anti-TNF therapy, history of anti-TNF therapy, fecal calprotectin level and endoscopic activity, leading to a c statistic of 0.55 [95% CI 0.51-0.59] (Table 1).

Table 1: Predictors of relapse in a pooled Cox regression analysis

Conclusion

Approximately 1 in 4 patients experience a relapse of UC within 1 year after anti-TNF cessation, increasing to 1 in 3 within 2 years. Continuation of thiopurines is associated with a reduced risk. A prediction model for relapse was developed in this large IPD meta-analysis cohort and may aid in shared decision-making on anti-TNF cessation. However, its limited discriminative ability underscores the need for further refinement, incorporating data on microscopic remission and molecular and immunological markers to better capture deeper disease control.

Introduction

Management of perianal fistulas in Crohn’s disease (CD) is challenging and requires a multidisciplinary approach, combining surgical drainage and biologic therapies, such as infliximab (IFX). Higher IFX trough concentrations have been associated with improved fistula healing rates. The subcutaneous (SC) formulation of IFX achieves 2–3 times higher and more stable trough levels compared to intravenous (IV) formulation. This study hypothesizes that SC IFX could enhance perianal fistula healing rates in CD patients.

Aims & Methods

REMSILAP study is part of the 3TLAP cohort, a French prospective multicenter observational study evaluating optimal therapeutic strategies for achieving clinical and radiological remission of perianal fistulas in CD at 12 months post-surgical drainage. The REMSILAP substudy focuses specifically on patients receiving SC IFX. Patients who received SC IFX after or within six months prior to surgical drainage were included. Baseline was defined as the day of surgical drainage. The primary outcome was the proportion of patients achieving complete clinical remission defined as Perianal Disease Activity Index (PDAI) fistula drainage subscore = 0 associated with PDAI activity restriction subscore <3 and absence of seton, and radiological remission at 12 months. Here, we present preliminary findings from REMSILAP.

Results

Among the 353 patients enrolled in the 3TLAP cohort, 54 were included in REMSILAP. The cohort consisted of 61.1% male patients, with a median age of 36 years and a median disease duration of 4.5 years. Penetrating disease (B3 phenotype) was present in 40.7%, and 33.3% had a history of surgical resection. At baseline, 40.7% of patients had quiescent disease regarding Harvey-Bradshaw index, while 5.6% had severe disease activity. Biologic exposure prior to inclusion was noted in 42.6%. Surgical drainage, with seton placement, was performed in 74.1% of patients. Forty-eight patients (88%) initiated SC IFX treatment after surgical drainage. Of the patients receiving SC IFX, 50% transitioned to SC IFX after less than three IV infusions. Among those on IV IFX at baseline, 20.4% were receiving a 10 mg/kg dose. Forty-three patients (79.6%) received SC IFX in combination with immunomodulators (azathioprine, methotrexate, or 6-mercaptopurine). The median duration of SC IFX treatment was 13.1 months, with treatment maintained for 67.5% of the follow-up period (mean: 19.3 ± 11.3 months). Forty-three patients (79.6%) were treated with a stable dose of 120 mg/14 days and 6 patients (11.1%) had an intensification of SC IFX dosage to 120mg / 7 days. At 12 months, 42 patients were evaluable for clinical outcomes. Complete clinical healing at 12 months was achieved in 11 patients (27.5%) and association of PDAI restriction subscore <3 and drainage subscore = 0 was found in 18 patients (42.9%). Thirteen patients (34.2%) from the 25 patients who had received at least 6 months of SC IFX treatment showed clinical healing at 6 months. Out of the 26 patients treated with at least 12 months of SC IFX treatment, clinical healing was achieved in 16 patients (61.5%) at 12 months. Among the 11 patients with clinical healing at 12 months, 8 (72.2%) were treated with SC IFX treatment following more than three IFX IV infusions. None of the 11 patients with available MRI date showed radiological healing at 12 months.

Conclusion

Subcutaneous infliximab following surgical drainage of Crohn’s disease perianal fistula demonstrates high treatment persistence and promising rates of fistula healing.

Disclosure

This study was funded by Celltrion Healthcare France