Introduction

Although an increased risk of acute pancreatitis (AP) in inflammatory bowel disease (IBD) has been previously described, there are only small series, and data on clinical management are lacking. We aimed to investigate the prevalence, etiology, and outcome of AP in IBD patients, including management, in a multicenter international study.

Aims & Methods

A two-step retrospective study was conducted involving 34 centers across Europe. The first step consisted of a survey questionnaire examining the number of AP (according to the Atlanta criteria) in adult IBD patients observed during a 10-year study period (2011-2020), and the second one in collecting data on IBD characteristics, onset of AP, etiology, clinical management, and outcome. The study's primary aim was to estimate the prevalence of AP in IBD patients based on the total number of IBD patients observed in the study period indicated in the survey form. Secondary aims included investigating the etiology of AP in IBD patients, the relationship between IBD medications and AP, the role of different imaging modalities in improving the diagnosis of pancreatic abnormalities, and the clinical outcome of AP. The study protocol has been disseminated through the ECCO (European Crohn’s and Colitis Organization) platform after review and support by Clinical Research Committee.

Results

The expected prevalence of AP in IBD patients, according to the survey results, was 1.13% (780 out of 68989). However, the number of entered patients in the database was 501 (0.73%), but only 398 (0.58%) fulfilled the inclusion criteria. The mean age was 33.6± 14.3, 52% were female, 225 (56.5%) were CD, and 173 (46.4%) were UC. AP was clinically mild in most (86.9%) and, when imaging was performed (n=347, 86.7%), a normal pancreatic gland was described in 81 (23.3%), whereas edematous AP in 218 (62.8%). The most frequent etiology was the drug-induced (220, 55.3%), due to azathioprine in 172 (77.8%), with AP occurring at 2 mg/kg dosage, after a median duration of 1 month. Other causes included gallstones (59, 14.8%) and autoimmune (8.3%). In 54 (13.5%) AP was considered idiopathic. During a median follow-up of 67 months [IQR 34-96] from the index episode, 52 (13%) patients had AP recurrence, and 6 (1.5%) patients progressed to chronic pancreatitis. According to a subgroup analysis by IBD type, CD patients were more often smokers, had a family history of IBD and/or pancreatic disease, extraintestinal manifestations (arthropathy), and a history of surgery, usually ileocecal resection. Ileal location with or without colonic involvement was present in 90.3%, with non-stricturing non-penetrating behavior in most (56%). Medications (66.7%) and gallstones (17.8%) were CD's most common AP etiologies. In contrast, no risk factors for AP were found in UC patients, and extensive disease was described in 102 (59%). The etiology differed significantly from the CD group (p < 0.0001), since in addition to medication (40.5%), autoimmune pancreatitis was found in 13.9% and idiopathic AP in 22%.

Conclusion

PANDORA study established a 0.58% prevalence of AP in IBD patients, lower than expected. The AP is usually mild both clinically and radiologically. In 14% of cases no imaging is performed, in 23% pancreas is normal, suggesting that the real prevalence might be even lower. An ileal location in CD and extensive colitis in UC are usually reported and azathioprine seems the most common cause of AP in this setting, especially a few weeks after its introduction.

Introduction

Factors influencing the exposure to targeted therapies (biologics/JAKi), intestinal resections and hospitalisations in newly diagnosed IBD patients have been scarcely studied.

Aims & Methods

Aim: To identify predictive factors of exposure to biologics/JAKi, surgeries, and hospitalisations within the first five years in IBD patients.
Methods: Prospective, population-based, nationwide registry. Adult patients diagnosed with IBD [Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)] during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years after diagnosis. Multivariate analyses were performed to identify the predictive factors for biologics/JAKi use, surgeries, and hospitalisations. To this end, only abdominal surgeries were analysed, and early treatment with immunomodulators or biologics/JAKi drugs were considered if these had been prescribed within the first six months of diagnosis.

Results

A total of 1,526 patients diagnosed with CD and 1,633 with UC were included. Regarding the predictors of exposure to biologics/JAKi treatments, we observed that younger age, more aggressive phenotype of CD and greater extent of UC were associated with a higher risk of exposure (table 1). Furthermore, smoking was associated with a higher likelihood of exposure to biologics/JAKi drugs in patients with CD (HR=1.33, 95%CI=1.11-1.60) while in UC patients it was associated with a lower risk (HR=0.56, 95%CI=0.35-0.89). Concerning surgeries (table 1), early treatment with immunomodulators was associated with a lower risk in patients with CD (HR=0.33, 95%CI=0.22-0.49), whereas early use of biologics/JAKi drugs was associated with a higher likelihood of surgery in patients with UC (HR=11.86, 95%CI=4.62-30.42). Finally, the exposure to biologics/JAKi drugs was associated with a lower risk of hospital admissions both in patients with CD (HR=0.37, 95%CI=0.24-0.56) and UC (HR=0.45, 95%CI=0.22-0.91) (table 1).

Table 1: Predictors of biologics/JAKi use (A), surgeries (B) and hospitalisations (C) in patients with Corhn´s disease (CD) and ulcerative colitis (UC)

Conclusion

The exposure to biologics/JAKi drugs is mediated by the more aggressive phenotype of CD, greater extent of UC, and younger patient age. The use of biologics/JAKi drugs, as currently practiced, is associated with a lower risk of hospitalisations but does not reduce the need for surgery, even when administered early. There is an unmet need for more accurate identification of patients who require these treatments to modify the natural course of the disease.

Disclosure

SR has received support for conference attendance, speaker fees, research support, and consulting fees from AbbVie, Adacyte, Faes Pharma, Ferring, Tillots, Galapagos, Janssen, Pfizer, and Lilly.
RF has received support for conference attendance, and research support from AbbVie, Faes Pharma, Ferring, Janssen, Pfizer, Takeda, and Galapagos.
RC: has received support from Janssen, Johnson&Johnson, Ferring, Abbvie, Falk, Pfizer y Galápagos.
AN: has received financial support for travelling and educational activities from Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma and Ferring.
JPG has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma.
MC has served as a speaker, or has received research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma.