Introduction

Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in chronic antibiotic refractory pouchitis (CARP) are lacking.^1-4 This ECCO-CONFER project collected cases of CARP treated with JAK inhibitors or S1P receptor modulators.

Aims & Methods

This retrospective multicentre study collected cases across Europe through the ECCO-CONFER project, including patients with ulcerative colitis (UC) diagnosis who underwent proctocolectomy with ileal pouch anal anastomosis (IPAA), treated with JAK inhibitors or S1P receptor modulators for CARP and at least three months of follow up. Main outcomes were steroid and antibiotics-free clinical response at three months (T3) for each drug, defined as clinical part of modified Pouchitis Disease Activity Index (mPDAI) reduction by ≥1 points, steroid and antibiotics-free clinical response at 1 year (T12) assessment, defined as mPDAI reduction by ≥2 points, steroid and antibiotics-free clinical remission (mPDAI=0) at T3 and T12, endoscopic response at T12 (improvement in PDAI Endoscopic Inflammation subscore reaching <3) and endoscopic remission at T12 (endoscopic PDAI ≤1). Non-response imputation was applied.

Results

Seventeen treatments with small molecules of CARP in 15 patients were collected from nine centres in seven countries. Eight patients were treated with tofacitinib; steroid and antibiotics-free clinical response at T3 was achieved in six patients (75%) and steroid and antibiotics-free clinical remission was achieved in five patients (62.5%). One patient discontinued tofacitinib for loss of response after eight months. Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50% of patients, steroid and antibiotics-free clinical remission in one patient (16.7%), endoscopic response in 60%, endoscopic remission in 60%. One patient was treated with filgotinib, neither steroid and antibiotics-free clinical response nor steroid and antibiotics-free clinical remission were achieved. Six treatments with upadacitinib were collected: at T3 steroid and antibiotics-free clinical response was achieved in 33.3% and steroid and antibiotics-free clinical remission was achieved in 16.7% of cases. Two cases were treated with ozanimod. At T3 steroid and antibiotics-free clinical response was achieved in one patient (50%) and steroid and antibiotics-free clinical remission was not achieved. No side effects were reported. Main baseline characteristics are summarized in Table 1.

Conclusion

In a multiple biologic-refractory population, small molecules might be a suitable treatment option for CARP. Based on current limited data, the use of JAK inhibitors should be further investigated.

References

¹Okano S et al. A case of refractory chronic pouchitis successfully treated with tofacitinib. Clin J Gastroenterol 2020
²Dalal RS et al. Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series. Inflamm Bowel Dis 2022;
³Akiyama S et al. Treatment of Chronic Inflammatory Pouch Conditions With Tofacitinib: A Case Series From 2 Tertiary IBD Centers in the United States. Inflamm Bowel Dis 2023
⁴Uzzan M et al. Effectiveness and safety of tofacitinib in patients with chronic pouchitis multirefractory to biologics: A multicenter cohort study from the GETAID. Dig Liver Dis 2023

Introduction

Acute severe colitis (ASC) is a medical-surgical emergency that can occur at any time during the course of chronic inflammatory bowel disease. It most commonly affects UC.

Aims & Methods

Aims: The aim of our work is to describe the particularities of GCA management during Crohn's disease (CD).
Materials and methods: This is a retrospective descriptive and analytical study spread over a 5-year period from January 2018 to January 2023. All patients who developed GAC during the course of Crohn's disease, whether inaugural or progressive, were included in our study.Data collected included age, sex, Crohn's disease location and phenotype, Lichtiger score before and after coticotherapy, second-line treatment, and use of surgery. SPSS 2.0 software was used for the statistical study. A binary logistic regression model was used for univariate analysis.

Results

Of the 424 IBD cases, 267 were being followed for Crohn's disease, of whom 38 (14.2%) patients presented with GAC. Mean age was 44.21 ±12.7 years (range 19-72 years). The F/H sex ratio was 1.9 (25 women to 13 men).The location of Crohn's disease was pancolic in 28 patients, ileocolic in 9, and ileocolic with high involvement in 1 patient. GCA was inaugural in 10 patients (26.3%), and complicated known Crohn's disease in 28 patients (73.7%). The mean Lichtiger score calculated at D0 was 11.84±1.8. The mean CRP value on admission was 89.8±47. Mean albumin was 27.9±3.6. Emergency abdomino-pelvic CT scans showed no complications such as colectasis, perforation or abscess in our series. All patients received IV methylprednisolone corticosteroids at a dose of 0.8 mg/kg/d, not to exceed 40 mg/d, with close clinico-biological monitoring. 21 patients (55.2%) were corticosensitive. The mean Lichtiger score calculated at D5 in corticosensitive patients was 8.7, with a mean CRP value at D3 of 36.8±12.

In univariate analysis, CRP >45 (on admission) and hypoalbuminemia were predictive factors for failure of IV corticosteroid therapy, with [OR=3.2 [1.3-5.2]; p=0.0005] and [OR = 1.31 [1.015-7,] p=0.002] respectively.Of the 17 (44.8%) cortico-resistant patients, 3 (7.9%) received emergency second-line treatment with Infliximab, and 15 (39.47%) underwent subtotal colectomy with ileostomy. Of these patients, one was scheduled after failure of second-line treatment. Good outcome was noted in 36 patients (94.7%). 2 cases of death (5.3%) were reported postoperatively. On discharge, 23 patients (63.9%) were treated with immunosuppressive agents or 13 (36.1%) with biotherapy.

Conclusion

Acute severe colitis can reveal or complicate Crohn's disease at any stage of its evolution. Management must be urgent, and requires medical-surgical coordination. The first-line medical treatment is intravenous corticosteroid therapy. Colectomy should be discussed at every stage of management.