Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: a cohort study

Background and Aim: The thiopurines azathioprine and 6‐mercaptopurine are effective in the management of patients with inflammatory bowel disease (IBD) in whom aminosalicylates, antibiotics and corticosteroids have failed to induce or maintain remission. Long‐term use of these agents has been linked to a greatly increased risk of non‐melanoma skin cancer and lymphatic cancer in organ transplant recipients. There is some evidence to suggest that IBD patients receiving thiopurines might be at increased risk of cancer. Our aim was to determine the incidence of cancer in a cohort of patients with IBD managed in our clinic, and to relate this to thiopurine exposure. Methods: We conducted a retrospective study based on the clinical and pathology records of patients attending a specialist IBD clinic at Groote Schuur Hospital, Cape Town, South Africa between 1960 and 2007. Results: We analyzed the records of 1084 patients. A total of 123 subjects (11.5%) had received thiopurine therapy. Cancer was identified in 51 patients (4.7%), including colorectal cancer (15 patients), melanoma (two patients), non‐melanoma skin cancer (seven patients) and non‐Hodgkin's lymphoma (five patients). A diagnosis of non‐melanoma skin cancer was significantly associated with thiopurine exposure (odds ratio 5.0, 95% confidence interval 1.1–22.8). Six of seven non‐melanoma skin cancers occurred in Caucasian patients, with a highly significant association with thiopurine use (odds ratio 12.4, 95% confidence interval 2.3–67.4). Conclusions: Patients with IBD who receive thiopurines are at increased risk of non‐melanoma skin cancer. The risk is highest in Caucasian patients, and is negligible in other groups.     

Safety Profile of Thiopurines in Crohn Disease: Analysis of 893 Patient-Years Follow-Up in a Southern China Cohort

Thiopurines have been associated with both clinical improvement and mucosal healing in treating Crohn disease (CD). Unfortunately, the high rate of adverse events (AEs) leading to drug withdrawal represents a major limitation in the use of these drugs.To evaluate the safety of thiopurines in patients with CD. To identify predictive factors associated with the development of thiopurine-induced AEs and withdrawal.This longitudinal cohort study examined patients from a university-based IBD referral center. Time-to-event analysis was performed with the Kaplan–Meier curve. Cox regression analysis was performed to identify potential predictive factors of AEs.Two hundred sixty-seven CD patients on thiopurines were included. A total of 143 AEs occurred at a median of 7.4 months (interquartile range, 3.7–15.3 months) after starting treatment. The cumulative incidence of AEs was 26%, with an annual risk of 4.3% per patient-year of treatment. The most frequent was leucopenia (41/267, 15.36%), followed by infections (29/267, 10.86%). Independent factors predictive of leucopenia were lower baseline hemoglobin (hazard ratio (HR), 0.34; 95% confidence interval (CI) 0.18–0.67) and the concomitant use of 5-aminosalicylic acid (HR, 3.05; 95% CI 1.44–8.76). Of the 28.44% (76/267) CD patients discontinued therapy, 14.61% due to AEs. A lower body mass index, the presence of extraintestinal manifestation, and the incidence of leucopenia independently predicted thiopurine withdrawal. In total, 37.5% of these patients restarted thiopurines and 52.3% of them had AEs again.About a quarter of patients on thiopurine therapy had AEs during follow-up and 1 of 7 patients had to discontinue thiopurines due to AEs.     

The risk of developing Crohn's disease after an appendectomy: a population-based cohort study in Sweden and Denmark

BACKGROUND: The relationship between appendectomy and Crohn's disease is controversial. A Swedish-Danish cohort study was conducted to assess the risk of developing Crohn's disease after an appendectomy. METHODS: 709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn's disease to 2004. Standardised incidence ratios (SIR) served as relative risks. RESULTS: Overall, 1655 Crohn's disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn's disease (SIR 1.00; 95% CI 0.80-1.25), the overall SIR of developing Crohn's disease was 1.52 (95% CI 1.45-1.59), being highest in the first 6 months (SIR 8.69; 95% CI 7.68-9.84). SIR diminished rapidly thereafter, with the risk of Crohn's disease reaching background levels after 5-10 years for Crohn's disease overall, as well as for Crohn's ileitis, ileocolonic Crohn's disease, Crohn's colitis and other/unspecified Crohn's disease. A long-term increased risk of Crohn's disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis. CONCLUSION: The transient increased risk of Crohn's disease after an appendectomy is probably explained by diagnostic bias.     

Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota

BACKGROUND & AIMS: The risk for colorectal cancer in Crohn's disease and ulcerative colitis patients from the United States currently is unknown. We estimated the risk for small-bowel and colorectal cancer in a population-based cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota, from 1940 to 2001. METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal and small-bowel cancer. The cumulative probability of cancer and standardized incidence ratios (SIR) were estimated using expected rates from Surveillance, Epidemiology, and End Results, white patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999. RESULTS: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38 expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6-6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118). CONCLUSIONS: The risk for colorectal cancer was not increased among ulcerative colitis patients overall, but appeared to be increased among those with extensive colitis. The colorectal cancer risk was increased slightly among Crohn's disease patients, who also had a 40-fold excess risk for small-bowel cancer.     

Drug-induced acute pancreatitis due to medications used for inflammatory bowel disease: A VigiBase pharmacovigilance database study

BackgroundNearly all medications used for inflammatory bowel disease (IBD) have been reported as causes of acute pancreatitis (AP), with the thiopurines being among the most frequently described. However, with the development of newer medications, thiopurine monotherapy has largely been replaced by newer immunosuppressive drugs. There are few data on the association between AP and biologic/small molecule agents.MethodsVigiBase, the World Health Organization's Global Individual Case Safety Report database, was used to assess the association between AP and common IBD medications. A case/non-case disproportionality analysis was performed and disproportionality signals were reported as a reporting odds ratio (ROR) with 95% confidence intervals (CIs).ResultsA total of 4,223 AP episodes were identified for common IBD medications. Azathioprine (ROR 19.18, 95% CI 18.21–20.20), 6-mercaptopurine (ROR 13.30, 95% CI 11.73–15.07), and 5-aminosalicylic acid (ROR 17.44, 95% CI 16.24–18.72) all had strong associations with AP, while the biologic/small molecule agents showed weaker or no disproportionality. The association with AP was much higher for thiopurines when used for Crohn's disease (ROR 34.61, 95% CI 30.95–38.70) compared to ulcerative colitis (ROR 8.94, 95% CI 7.47–10.71) or rheumatologic conditions (ROR 18.87, 95% CI 14.72–24.19).ConclusionsWe report the largest real-world database study investigating the association between common IBD medications and AP. Among commonly used IBD medications including biologic/small molecule agents, only thiopurines and 5-aminosalicylic acid are strongly associated with AP. The association between thiopurines and AP is much stronger when the drug is used for Crohn's disease compared to ulcerative colitis and rheumatologic conditions.     

High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease

BackgroundGene polymorphism of thiopurine methyltransferase (TPMT) correlates with decreased enzyme activity which determines a significant risk of adverse effect reactions (ADR) in patients treated with thiopurines. The aim of this study was to investigate TPMT genotype and phenotype status in patients with inflammatory bowel diseases (IBD).MethodsFifty-one consecutive out-patients with IBD were genotyped for the following allelic variants: rs1800462 (referred as TPMT*2 allele), rs1800460 (referred as TPMT *3B allele), and 1142345 (referred as TPMT *3C allele). Red blood cell TPMT activity was measured using a competitive micro-well immunoassay for the semi-quantitative determination of TPMT activity in red blood cells (RBC) by means of a 6-MP substrate.ResultsPolymorphism of TPMT was found in 5 out of 51 patients (10%; 95% CI 2%–18%), three heterozygous and two homozygous carriers. Six patients (11.8%; 95% CI 2.4%–19.5%) displayed very low, 12 (23.5%; 95% CI 11.4%–34.5%) intermediate, and 33 (64.7%; 95% CI 52%–78%) normal/high TPMT activity. There were no differences between TPMT genotype and phenotype groups according to age, type of disease, smoking, and chronic medications. A 71% (95% CI 61%–81%; κ = 0.45) concordance rate was found between genotype and phenotype status. Six out of 27 (22%) current or past users of azathioprine developed ADR, with three (50%) displaying TPMT genotype and/or phenotype alterations.ConclusionCompared to the general population, IBD patients may have significantly higher prevalence of TPMT polymorphism and, even more, low activity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.     

Early measles virus infection is associated with the development of inflammatory bowel disease

OBJECTIVE: The measles virus has been implicated as a possible etiological agent in the development of inflammatory bowel disease (IBD). Measles infection at an early age is associated with subacute sclerosing panencephalitis, a degenerative neurological condition caused by persistent measles infection of the central nervous system. We sought to determine whether infection with measles virus at an early age was also associated with an increased risk of developing IBD. METHODS: Patients with measles infection diagnosed before the age of 5 yr were identified through the diagnostic indices of the Mayo Clinic and the Rochester Epidemiology Project. A questionnaire was used to ascertain a subsequent history of IBD, which was confirmed by records from the subjects' physicians. The risks of developing Crohn's disease and ulcerative colitis were calculated relative to expected rates for these conditions in the Olmsted County, Minnesota population. RESULTS: Of 1164 eligible cases, 662 (57%) completed the questionnaire. There were six confirmed cases of Crohn's disease and six of ulcerative colitis. The expected number of cases was 1.9 for Crohn's disease (standardized incidence ratio [SIR] 3.1, 95% confidence interval [CI] 1.1-6.8) and 2.0 for ulcerative colitis (SIR 3.0, CI 1.1-6.5). There was a trend towards a higher risk of developing IBD with an earlier age of infection. CONCLUSIONS: Early measles infection is associated with an increased risk of developing Crohn's disease and ulcerative colitis. The risk may be higher with earlier infection.     

Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease

AIM To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo.METHODS The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease(IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBD patients on a thiopurine, 19 IBD patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBD patients on a thiopurine, 17 IBD patients not on a thiopurine, and 49 healthy screening colonoscopy recipients.RESULTS Complete blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBD patients who were taking thiopurines at the timeof sampling. This reduction was restricted to CD3-negative lymphocytes, wherein both natural killer(NK) and B cells were significantly reduced among thiopurine recipients. Among CD19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in CD8+ T cells, mucosa-associated invariant T(MAIT) cells, invariant natural killer T(i NKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells(Tregs) or na?ve CD4+ T cells. However, patients with IBD had significantly more circulating FOXP3+, Helios+ Tregs and fewer iN KT and MAIT cells than healthy controls. CONCLUSION Thiopurine use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBD patients.     

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: Results from a population-based cohort in Eastern Europe

Background and aimsPrior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008.MethodsData from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD.ResultsOf the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44–4.26). No cases have been exposed to either azathioprine or biologicals.ConclusionsThe overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.     

Prevalence of Methylenetetrahydrofolate Reductase Polymorphisms in Young Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) has been related to mutations of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in the metabolism of folate and methionine, both of which are important factors in DNA methylation and synthesis. A mutated MTHFR genotype was associated with increased toxicity of methotrexate treatment. The objective of this study was to verify, in a population of young patients with IBD, the presence of an association among mutations in the MTHFR gene, the incidence of IBD, and the risk of adverse events during the treatment with thiopurines azathioprine (AZA) or 6-mercaptopurine (6MP). Ninety-two patients with IBD were enrolled; 63 were treated with thiopurines; patients and 130 controls were genotyped for MTHFR mutations by PCR-based methods. The incidence of mutations in the MTHFR gene was not different between patients with IBD and control subjects; the mutated genotype was not associated with an increased risk of toxicity during thiopurine treatment. This research was supported by grants from the Italian Ministry of University and Scientific Research and the Italian Ministry of Health.     

Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study

BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1) and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION: Patients with chronic inflammatory bowel disease seem to be at increased risk of acute pancreatitis. Further validation and refinement of this registration-based study are needed.     

Non-calculus suppurative cholangitis in Danish patients with inflammatory bowel disease

BACKGROUND/AIMS: We examined the risk of non-calculus suppurative cholangitis in patients with inflammatory bowel disease in the entire Danish population. METHODOLOGY: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis as registered in the Danish National Registry of Patients from January 1, 1977 to December 31, 1992. We compared the observed number of patients hospitalized with suppurative cholangitis with expected numbers on the basis of age, gender, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,317 eligible patients with inflammatory bowel disease were discharged during the study period. Among these were 52 cases of non-calculus suppurative cholangitis. The incidence rate of non-calculus suppurative cholangitis in the cohort with inflammatory bowel disease was 46.1 per 100,000 person-years. The standardized incidence ratio (SIR) for suppurative cholangitis was increased similarly for patients with Crohn's disease [SIR=6.7, 95% confidence interval (CI): 3.1-12.7] and for patients with ulcerative colitis (SIR=6.6, 95% CI: 4.7-9.1). The highest relative risk was found in male patients younger than 40 years of age, for both Crohn's disease and ulcerative colitis (SIR=70.5 and 78.7, respectively). CONCLUSIONS: Patients with inflammatory bowel disease have an increased risk of non-calculus suppurative cholangitis.     

Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

AIM: To evaluate the relationship between thiopu- rine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD). METHODS: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and-intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: Nine studies that investigated a total of 1309 part...     

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.     

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment

Background and AimsLittle is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain.MethodsAmong 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI.ResultsAmong the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12–42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1–2.6), EIMs (HR 1.5, 95% CI: 1.0–2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5–3.4) and need for CsA (HR 2.4, 95% CI: 1.6–3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2–7.8) when AZA/MP started in the first 33 months after UC diagnosis.ConclusionsNearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC.     

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

The use of thiopurines in inflammatory bowel disease(IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor(antiTNF) agents, and maintenance of remission and postoperative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.     

A meta-analysis on the influence of inflammatory bowel disease on pregnancy

BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. AIM: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. DESIGN: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. Patients and SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.     

Use of thiopurines is not a risk factor for post-ERC pancreatitis in patients with primary sclerosing cholangitis

IntroductionRisk of post-ERC pancreatitis (PEP) in patients with primary sclerosing cholangitis (PSC) is 1–7.8%. PSC is often associated with inflammatory bowel disease and autoimmune hepatitis, which are usually treated with thiopurines. The role of thiopurines in PEP risk is still unclear.Aims and methodsWe evaluated the thiopurine use in PEP. The data of 354 PSC patients who underwent 985 ERCs between 2009 and 2018 were collected. 177 patients treated with thiopurines (study group, SG) and 177 controls (CG) were matched with a propensity score (PSM). Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated. Multivariable logistic regression analysis and generalized linear mixed model were performed. The P-value <0.05 was significant.ResultsIn matched data, 472 ERCs were performed in SG and 513 in CG. Thiopurines were used in 373/472 (79.0%) ERCs in SG. The PEP rate was 5.3% in SG and 5.7% in CG (p = 0.889). Unintentional pancreatic duct cannulation (OR 1.28, 95%CI 1.07–1.51, p = 0.004), and periampullary diverticulum (OR 4.87, 95%CI 1.72–11.98, p = 0.001) increased the risk of PEP.ConclusionPrior or present thiopurine use did not increase the risk of PEP.