JAK inhibitors and S1P receptor modulators for the treatment of antibiotic refractory chronic pouchitis: an ECCO CONFER Multicentre Case Series

Background: Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in chronic antibiotic refractory pouchitis (CARP) are lacking. This ECCO-CONFER project collected cases of CARP treated with JAK inhibitors or S1P receptor modulators.
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 50.0% of patients, steroid and antibiotics-free clinical remission in one patient (16.7%), endoscopic response in 50.0% and endoscopic remission in 50.0%. 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 (50.0%) and steroid and antibiotics-free clinical remission was not achieved. No side effects were reported. Baseline characteristics and results are summarized respectively in figure 1 and table 2.
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.