Use Of Thiopurines Research Articles

The Ulcerative Colitis Endoscopic Index of Severity is Useful to Predict Medium- to Long-Term Prognosis in Ulcerative Colitis Patients with Clinical Remission.

The ulcerative colitis endoscopic index of severity [UCEIS] is a validated scoring system. Nevertheless, few studies have investigated its usefulness in clinical settings. In this study, we aimed to predict the clinical prognosis of patients with ulcerative colitis [UC] in clinical remission using the UCEIS. A total of 285 UC patients who underwent a colonoscopy between April 2012 and March 2013 were enrolled. We reviewed clinical characteristics and endoscopic scores at the time of the colonoscopy and checked the clinical remission rate of the patients until September 2015. Clinical remission and recurrence were defined as a partial Mayo score of ≤1 and ≥3, respectively. UCEIS was strongly correlated with the Mayo endoscopic score [r=0.93], moderately correlated with clinical severity [r=0.64] and mildly correlated with C-reactive protein [r=0.34]. The recurrence rate increased gradually as it became more endoscopically severe [5.0% for UCEIS=0, 22.4% for UCEIS=1, 27.0% for UCEIS=2, 35.7% for UCEIS=3 and 75.0% for UCEIS=4-5] in patients with clinical remission. UCEIS and the concomitant use of thiopurine were independent factors predicting clinical recurrence. A multivariate analysis indicated that the absence of bleeding [p≤0.001] and the absence of mucosal damage [p<0.001] in a colonoscopy were independent factors for prolongation of clinical remission. The UCEIS is useful to predict the medium- to long-term outcomes of UC patients with clinical remission. The absence of bleeding or mucosal damage is important for maintaining clinical remission.

EBV Status and Thiopurine Use in Pediatric IBD.

Epstein Barr virus (EBV) is a human herpes virus that infects 90% of the world's population and has been linked to the development of lymphoproliferative disorders (LPDs) and immunosuppression. Primary EBV infection in patients with IBD on thiopurines is a risk factor for LPD, including lymphoma. We aimed to describe EBV status in a pediatric population with IBD with an emphasis on those initiating thiopurines. Electronic medical records and EBV serologies were reviewed and categorized into asymptomatic screening versus suspicion for acute infection. EBV status before therapy was described by sex, age, and therapeutic regimen. Descriptive statistics and univariate analysis were employed. Only 150 (22%) of our 688 pediatric patients with IBD had documented EBV status regardless of age or treatment regimen. Only 17% were assessed for suspicion of acute infection and 83% for screening. Sixty-four (52%) screened patients were checked before starting any treatment and only 40% were immunoglobulin (Ig)G positive. There was no difference in mean age between the seronegative and seropositive group. The majority (63%) of thiopurine-treated patients were IgG negative before starting therapy. Eighty percent of primary EBV infections occurred on thiopurines at a mean (SD) of 2 ± 1.5 years after initiating therapy. The majority of our pediatric patients with IBD with documented EBV status were IgG negative at thiopurine initiation. Thiopurines were also associated with primary EBV infection. EBV status may be an important determinate of whether physicians prescribe thiopurines given the risk of primary EBV infections and lymphoproliferative diseases.

P635. Personalised prophylactic use of thiopurines prevented surgical recurrence in patients with Crohn’s disease after intestinal resection

P635. Personalised prophylactic use of thiopurines prevented surgical recurrence in patients with Crohn’s disease after intestinal resection

Thiopurine metabolite testing in inflammatory bowel disease.

Thiopurine use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose, and metabolite levels in a real world setting. Patients identified from pathology databases (2007-2012) at two tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review. A total of 169 patients were included. 6-Thioguanine (TGN) levels were sub-therapeutic in 52%, therapeutic in 34%, and supratherapeutic in 14%. Test indication was active disease (79%), adverse effect (11%), or adherence assessment (7%). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) versus 447 (+/- 117.7) pmol/8 × 10(8) RBC, P = 0.05). Weight-based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5% vs standard dose 35.4%), but was significantly associated with shunting toward 6-MMP (23.1% vs 6.8%, P = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86% of patients with active disease and subtherapeutic levels and in 68% of tested patients overall. Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight-based dosing did not increase rates of therapeutic levels but was associated with increased 6MMP shunting.

Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer.

Immune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs. To determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti-tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC. In this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012. Exposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery. A second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models. Among 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95% CI, 0.76-2.44), respectively. Methotrexate use is associated with an increased risk of a second NMSC. Anti-TNF use may increase the risk of a second NMSC when used with methotrexate for RA. Further long-term studies are required before one can conclude that thiopurine and/or anti-TNF do not increase the risk of a second NMSC in patients with IBD.

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 (anti-TNF) agents, and maintenance of remission and post-operative 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.

Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer.

Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease.

Review article: the natural history of paediatric-onset ulcerative colitis in population-based studies.

A better knowledge of the natural history of disabling chronic diseases is essential to improve patient management, evaluate the impact of treatment strategies and provide predictors for disabling disease and comprehensive information for patients. To summarise our current knowledge issued from population-based studies of the natural history of ulcerative colitis (UC) in children. We searched MEDLINE (source PubMed) and international conference abstracts, and included all population-based studies that evaluated long-term outcome of paediatric-onset (<17years at diagnosis) UC. A total of 26 population-based studies were considered in this review from the total of 61 articles or abstracts screened. Most patients presented disease extension and about two-thirds of patients had pancolitis at the end of follow-up. One-half of patients experienced extra-intestinal manifestations and primary sclerosing cholangitis was observed in 5-10% of patients. Overall, patients did not appear to have any significant growth retardation or delayed puberty. About two-thirds of patients required corticosteroid therapy and up to 25% were steroid dependent. An increased use of thiopurines was observed and the most recent data indicate that up to one-half of patients were exposed to thiopurines and 10-30% were exposed to anti-tumour necrosis factor. One-half of patients required hospitalisations and 20% of patients required colectomy after a follow-up of 10years. Paediatric-onset UC is characterised by a high rate of disease extension. About 20% of patients had been operated at 10-year follow-up. New population-based studies are needed to evaluate the impact of new treatment strategies comprising immunosuppressants and biologics.

Impact of New Treatments on Hospitalisation, Surgery, Infection, and Mortality in IBD: a Focus Paper by the Epidemiology Committee of ECCO.

The medical management of inflammatory bowel disease has changed considerably over time with wider use of immunosuppressant therapy and the introduction of biological therapy. To what extent this change of medical paradigms has influenced and modified the disease course is incompletely known. To address this issue, an extensive review of the literature has been carried out on time trends of hospitalization, surgery, infections, cancer, and mortality rates in inflammatory bowel disease [IBD] patients. Preference was given to population-based studies but, when data from these sources were limited, large cohort studies and randomised controlled trials were also considered. In general, data on hospitalisation rates are strikingly heterogeneous and conflicting. In contrast, the consistent drop in surgery/colectomy rates suggests that the growing use of immunosuppressants and biological agents has had a positive impact on the course of IBD. Most clinical trial data indicate that the risk of serious infections is not increased in patients treated with anti-tumour necrosis factor alpha [TNFα] agents, but a different picture emerges from cohort studies. The use of thiopurines increases the risk for non-melanoma skin cancers and to a lesser extent for lymphoma and cervical cancer [absolute risk: low], whereas no clear increase in the cancer risk has been reported for anti-TNF agents. Finally, the majority of studies reported in the literature do not reveal any increase in mortality with immunosuppressant therapy or biologicals/anti-TNF agents.

A Case of Hepatosplenic Gamma-delta T Cell Lymphoma with Intravascular Lymphoma Like Features in a Young Male With Autoimmune Hepatitis

Hepatosplenic gamma delta T-cell lymphoma (HSGDTL) is a rare and aggressive hematologic malignancy that has been associated with long term use of immunosuppressive agents. Here we report a 22-year-old male on azathioprine and prednisone for autoimmune hepatitis who presented to hospital with abdominal pain, night sweats and 20lbs of weight loss. On exam he had hepatomegaly and splenomegaly but no lymphadenopathy. His initial lab tests were WBC 5.39 x 109/L, Hb 70 g/L, platelets 25 x 109/L, total bilirubin 74 μmol/L, AST 151 U/L, ALT 55 U/L and LDH 5932 U/L. He had marked hepatosplenomegaly without lymphadenopathy on abdominal CT scan. Bone marrow and liver biopsies confirmed the presence of HSGDTL. Unfortunately he did not respond to multiple cycles of chemotherapy and passed away. On autopsy he had multiorgan involvement of an intravascular lymphoma like (IVLL) T-cell population. There are no definitive risk factors for HSGDTL but an association with immunosuppressive agents has been well documented in renal transplant recipients and patients with inflammatory bowel disease (IBD). Specifically, the use of thiopurines for at least two years in young males with IBD has been linked to an increased risk of developing HSGDTL. To our knowledge, however, previous cases of HSGDTL in autoimmune hepatitis patients have been minimally reported in the literature. Unique to our case was the finding of an intravascular lymphoma like component on autopsy that was present in tissue samples from the patient's lungs, kidneys, heart, thyroid and testicles. As far as we know, a widespread multi-organ intravascular lymphoma in a HSGDTL patient is exceedingly rare. In fact we found only one other case in the literature. Therefore, it is difficult to assess the impact of this finding. It is possible the presence of intravascular lymphoma represents a subtype of HSGDTL and may provide insight into the aggressive nature of this disease. We must also consider an association between autoimmune hepatitis and HSGDTL with IVLL component independent of immunosuppressive therapy. However, future research into this little known and seldom reported malignancy will be required to fully appreciate these findings. Overall, we hope our case report will contribute to better understanding the association between T-cell lymphoma and long term use of immunosuppressive agents as well as identify new populations, specifically autoimmune hepatitis patients, who may be at risk of developing this deadly disease.Figure 1

Inflammatory bowel disease-specific pregnancy knowledge of gastroenterologists against general practitioners and obstetricians.

Patients with inflammatory bowel disease (IBD) tend to have smaller family sizes. Health care professionals (HCPs) may inadvertently provide inaccurate advice to patients resulting in voluntary childlessness or unfavourable pregnancy outcomes. The study aims to objectively measure IBD-specific pregnancy-related knowledge of general practitioners (GPs) and obstetricians/gynaecologists (OB/GYNs) in comparison with gastroenterologists (GEs) using the validated Crohn's and Colitis Pregnancy Knowledge (CCPKnow) questionnaire. GPs, OB/GYNs and GEs in two Australian states completed the CCPKnow (range 0-17) and demographic questionnaires. The CCPKnow addresses issues pertaining to conception, IBD inheritance, risk of congenital abnormalities, medication use in the peri-conceptual period, pregnancy and breastfeeding, and mode of delivery. In total, 337 HCPs responded. GPs (n = 188/2086) and OB/GYNs (n = 94/228) had significantly lower knowledge than GEs (n = 55/165) for the composite CCPKnow (medians 11, 13 and 17, respectively, p < 0.001), and almost all domains. GEs were the only group to attain a median CCPKnow score in the top category (14-17). More than 70% of GPs and OB/GYNs expressed discomfort with initiation of IBD medications around conception/pregnancy. GPs (43.6%) and OB/GYNs (45.7%) perceived thiopurine use to be unsafe during pregnancy and to cause serious harm to the baby. Our study demonstrates that GPs and OB/GYNs have inadequate and variable IBD-specific pregnancy-related knowledge including use of IBD medications. These results support the need for GEs' prime role in a team-based management for IBD patients who are pregnant or planning pregnancy.

Monitoring for Extra-Intestinal Cancers in IBD.

Multiple studies have demonstrated an increased risk for extra-intestinal cancers in inflammatory bowel disease (IBD) patients, mainly from treatment modalities. Prominent cancers that are related to IBD treatment include the following: lymphoproliferative disorders associated with thiopurine use, hepatosplenic T cell lymphoma primarily in younger male patients on thiopurines and anti-tumor necrosis factor (TNF) agents, non-melanoma skin cancers in patients treated with thiopurines and anti-TNF agents, and melanomas in patients who are on monotherapy with anti-TNF agents. In addition, women with IBD may have higher rates of cervical dysplasia and cervical cancer. The focus of this review is to provide a comprehensive overview on extra-intestinal cancers in IBD patients and how to monitor for these malignancies.

Impact of early thiopurines on surgery in 2770 children and young people diagnosed with inflammatory bowel disease: a national population-based study.

The role of early thiopurine treatment in inflammatory bowel disease (IBD) is unproven. To quantify the impact of timing and duration of thiopurines on the risk of first surgery in children and young people with IBD using a population-based cohort. We constructed an incident cohort of children and young people aged <25years, diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) from 1990 to 2009. We used Cox proportional hazards modelling to determine the impact of early thiopurine use, commenced within a year of diagnosis on risk of first surgery. We identified 1595 and 1175 incident cases of CD and UC respectively with a mean length of follow-up of 4.3years/person. There were 216 (13.5%) and 73 (6.2%) surgeries for CD and UC patients between 1990 and 2009 respectively. In CD among thiopurine users, the absolute risk of surgery at 5years for early thiopurine use vs. late was 15.3% (95% CI: 10.5-22.1) vs. 22.1% (95% CI: 18.1-26.9) respectively. After adjustment, the early use of thiopurines was associated with a reduction in risk of first surgery of 39% (HR 0.61, 95% CI: 0.41-0.91) over the 20-year study period. In UC, early thiopurine use offered no additional benefit. In Crohn's disease, early treatment with thiopurines in children and young people is associated with an appreciable reduction in the risk of surgery, but early treatment does not reduce surgical risk in UC.

Postoperative Effects of Thiopurines in Patients with Intestinal Behçet's Disease.

No studies have heretofore specifically focused on the efficacy of postoperative thiopurine therapy in intestinal Behçet's disease (BD). We conducted this study to assess the clinical effects of postoperative thiopurines in patients with intestinal BD. We reviewed the medical records of all patients with intestinal BD who had undergone bowel resection surgery in a single tertiary academic medical center between 1991 and 2013. The cumulative probabilities of clinical recurrence were calculated using the Kaplan-Meier method, and predictive factors for recurrence were assessed by multivariate analysis. A total of 77 patients with intestinal BD received 5-ASA (n = 50, 64.9%) or thiopurine (n = 27, 35.1%) therapy after surgery at our center. The postoperative recurrence rate was lower in patients who received postoperative thiopurines (P = 0.050). The hazard ratio for recurrence was 0.636 (95% confidence interval 0.130-1.016, P = 0.053) for postoperative thiopurine use compared with postoperative 5-ASA. However, the rates of re-operation, re-admission, and death were not significantly different between the 5-ASA and thiopurine groups. Thiopurine therapy after surgery exhibited a modest effect in preventing recurrence in intestinal BD patients. More patients, long-term follow-up, and a randomized controlled design are necessary to validate the effectiveness of postoperative thiopurines in patients with this disease.

Prevalence of Antibodies Against JC Virus in Patients With Refractory Crohn’s Disease and Effects of Natalizumab Therapy

Natalizumab, a humanized antibody against the α4 integrin subunit, effectively induces and maintains remission in patients with Crohn's disease (CD) refractory to conventional treatments. Progressive multifocal leukoencephalopathy is a rare but fatal brain infection caused by John Cunningham (JC) virus and has been associated with natalizumab use. We assessed the prevalence of and risk factors for antibodies to JC virus in serum of patients with refractory CD who were candidates for, or already were receiving, natalizumab. We also assessed the effects of natalizumab treatment of these patients. In a retrospective study, we analyzed clinical charts from 191 patients with CD (74 males; mean age, 38.7 y; mean duration of disease, 14.9 y) tested for serum JC virus antibody from December 2012 through May 2014 at 2 medical centers in the United States. We calculated JC virus antibody prevalence and compared the characteristics of patients who tested negative vs those who tested positive, to identify risk factors. We also assessed the rate of subsequent natalizumab use, surgery, and seroconversion during natalizumab therapy. A total of 129 of the patients (67.5%) tested positive for serum JC virus antibody. Multivariate analysis showed that past use of thiopurine was a risk factor for testing positive for JC virus antibody (odds ratio, 7.8; 95% confidence interval, 2.0-30.4; P = .003). Twenty-two of the patients who tested negative for JC virus antibody (35.5%) and 16 of the 129 patients who tested positive (12.4%) had been treated with natalizumab. Cox regression analysis determined that natalizumab use was the only factor associated with avoiding subsequent surgery (hazard ratio, 0.23; 95% confidence interval, 0.06-0.98). Seroconversion (from testing negative to positive for JC virus antibody) occurred in 1 of the 22 patients (4.5%) who initially tested negative during natalizumab therapy. The prevalence of CD patients exposed to JC virus is comparable with that of the general population. In this retrospective study, prior thiopurine use was associated with an increased risk for testing positive for JC virus antibody. Natalizumab use reduced the risk of subsequent surgery.

Papel actual de los inmunomoduladores convencionales en la enfermedad inflamatoria intestinal pediátrica

Pediatric Inflammatory Bowel Disease (P-IBD) has its own characteristics and early, intensive and sustained treatment is recommended. Immunomodulator treatment is indicated for maintenance of remission in P-CD (Pediatric Crohn's Disesase) treated with exclusive enteral nutrition (EEN) to induce remission and P-UC (Pediatric Ulcerative Colitis) that requires steroids to induce remission. Combo therapy is recommended for patients at high risk of complications; however, individualized treatment and the assessment of adverse events is mandatory. By now, the use of thiopurines is not justified for the prevention of loss of response to anti-TNF and antibody formation. Larger pediatric prospective studies are needed.

Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro.

IntroductionThe use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this affects in vitro cytotoxicity.MethodsHuman hepatoma cells (Huh7, HepG2 and HepaRG) were incubated with increasing concentrations of thiopurines, 5-ASA or allopurinol. Water-soluble tetrazolium salt-1 (WST-1) cytotoxicity assays were used to calculate cell survival curves and half maximal inhibitory concentrations (IC50). Combination experiments with thiopurines with a fixed dose of 200 μM 5-ASA or 100 μM allopurinol were conducted in HepaRG cells. Caspase-3/7 activation was evaluated, and single cell electrophoresis analysis was performed.ResultsA time- and dose-related cytotoxic effect was seen with azathioprine (AZA) in all hepatoma cells, whereas Huh7 and HepG2 cells did not show toxicity to 6-mercaptopurine (6-MP). HepaRG cells expressed the highest levels of drug metabolising enzymes, and therefore, combination experiments were conducted in HepaRG cells. Addition of a non-toxic dose of allopurinol resulted in a twofold to threefold increased cytotoxicity of all thiopurines, which seemed to be mediated by apoptosis/DNA damage.ConclusionThe addition of allopurinol to thiopurines leads to a two–threefold increased cytotoxicity in HepaRG cells.

Optimizing the use of thiopurines in inflammatory bowel disease.

Immunomodulator drugs, of which thiopurines can be considered the backbone, are widely used in the treatment of inflammatory bowel disease. They have been shown to be highly effective and safe; however, a significant proportion of patients are deemed to have a poor response or suffer adverse reactions. Knowing how to monitor and optimize thiopurine therapy in these scenarios is crucial to effective management. We discuss the metabolism of thiopurines, the use of enzyme/metabolite testing to guide treatment, as well as strategies to circumvent toxicity and side effects, such as allopurinol coprescription. The indications, use in pregnancy, safety profile and duration of thiopurine therapy are also discussed.

Combination Therapy with Infliximab and Thiopurine Compared to Infliximab Monotherapy in Maintaining Remission of Postoperative Crohn's Disease

Background and Aims: Infliximab is an efficacious agent used for the induction and maintenance of remission in Crohn's disease (CD), and recent studies suggested that it may also prevent the recurrence of this disease after surgery. The present study was performed to assess the efficacy and safety of infliximab in the postoperative setting, and to identify whether combination treatment with thiopurines had any additional beneficial effect as compared to mono-therapy. Methods: We performed a retrospective cohort study to compare the efficacy of infliximab mono-therapy and combination treatment with a thiopurine in preventing recurrence after surgery. Results: Forty-one patients who received infliximab as maintenance treatment following surgery from May 2002 to April 2010 were identified. Twenty-four were naive to infliximab, and 17 who underwent surgery during infliximab treatment were continued on it following surgery. The median follow-up period was 27 months (range 12-66 months). All patients continued infliximab as maintenance treatment, but 10 required dose intensification due to clinical recurrence. Kaplan-Meier analysis demonstrated that the use of concomitant thiopurine was correlated with the continuation of infliximab treatment at an 8-week interval (log-rank test p = 0.018). The rate of adverse event was 9.8% with no patient experiencing severe adverse reactions. Conclusion: Infliximab appears to be safe and it prevented clinical recurrence after surgery. Concomitant thiopurine use predicted response toward continuation of therapy at an 8-week interval. Prospective controlled studies to assess the efficacy of combination treatment in the postoperative setting are warranted.

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