Introduction

Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting litterature about thiopurines maintaining long-term remission in patients with active IBD.The aim of this study is to determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy.

Aims & Methods

We performed a retrospective analysis of adult patients diagnosed from 2004 to 2016,. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3 years, with a minimum follow-up period of 7 years. The Mayo score (MS) and Crohn disease activity index (CDAI) were used to assess disease activity in UC and CD patients, respectively. The primary endpoint was sustained clinical remission on thiopurines at 7 years of follow-up . This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as CDAI > 150 in CD and MS > 3 in UC.

Results

We evaluated 94 patients (52 female, 41 male sex ratio H/F = 0,7 mean age 35.9 ± 15 years) .Among our patients 12 were smoking, 52 among our patients were diagnosed with Crohn's disease (CD), 38 ulcerative colitis (UC), 4 inclassed IBD. Among our patients 43 (45.7%) were treated with azathioprine monotherapy . At 7 years of follow up, 29 patients (67%) remained in clinical remission on thiopurine monotherapy. Three patients presented complications such as deep collection in two cases and ileal stenosis in one case. Eleven patients (25%) stopped treatment for haematological toxicity in 8 cases, liver toxicity in two cases and digestive intolerance in one case.

Conclusion

This analysis demonstrates that there is good sustainability of clinical remission in IBD patients on thiopurine monotherapy. However, this treatment was poorly tolerated by the quarter of patients.

Disclosure

Nn conflict of interest

Introduction

Aims & Methods

Results

Conclusion

References

Introduction

Chronic fatigue (CF) is prevalent among patients with ulcerative colitis (UC) and Crohn's disease (CD), but the influence of the disease activity is not established.

Aims & Methods

The primary aim of this study was to evaluate the prevalence and probability of chronic fatigue (CF) in patients with CD and UC one year after diagnosis, stratified by different measures for disease remission (symptomatic, biochemical, endoscopic, and histological). Additionally, we aimed to evaluate factors associated with chronic fatigue among patients in endoscopic/radiological remission.

Patients ≥18 years with CD and UC were recruited from the Inflammatory Bowel Disease South-Eastern Norway (IBSEN III) study, a population-based, observational inception cohort. Fatigue was assessed using Fatigue Questionnaire (FQ), and CF was defined as a dichotomized score of ≥4 with a duration of ≥6 months. Only patients with complete FQ data, without history of colectomy, were eligible for inclusion. Binary logistic regression analyses were used to examine the probability of CF for various indicators of remission, including i) symptomatic remission (Harvey–Bradshaw index score <5 for CD and Simple Clinical Colitis Activity Index score <3 for UC), ii) biochemical remission (Fecal calprotectin ≤ 250 µg/g), iii) endoscopic/radiological remission (Mayo endoscopic score 0 in UC, and endoscopically verified absence of inflammation combined with normal intestinal MRI/CT in CD), and iv) histological remission (normal histology in all mucosal biopsies). Additionally, in patients with endoscopic/radiological remission, associations between CF and selected clinical factors were evaluated using binary logistic regression analysis.

Results

In total, 711/1416 patients with CD or UC diagnosis were included (CD: 33.8%, UC: 66.2%). Among them, 619 (87.1%) underwent colonoscopy, intestinal MRI/CT and/or fecal calprotectin testing. Prevalence of CF stratified by different indicators of remission is presented in table 1. In univariate binary logistic regression analysis regarding measures for disease remission, the probability of CF was only significantly reduced in patients with UC in symptomatic remission (OR: 0.48 (0.30, 0.77), p=0.003). Among patients with CD and UC in endoscopic/radiological remission (n=181), CF was independently associated with current biological treatment (OR: 2.92 (1.002, 8.49), p=0.05) and sleep disturbance (OR: 6.23 (2.03, 19.14), p=0.001) in multivariate logistic regression.

Conclusion

The probability of CF one year after diagnosis was not associated with either low fecal calprotectin level, normal endoscopic/radiological examinations, or normal histology. Among patients with UC, but not CD, symptomatic remission was associated with a reduced probability of CF. For patients in endoscopic/radiological remission, CF was independently associated with sleep disturbances and current biological treatment.

Disclosure

All authors report no conflict of interest.

Introduction

Thiopurine therapy is a cornerstone in the treatment of patients with inflammatory bowel disease (IBD).

Aims & Methods

We aimed to assess the effect of thiopurines on the risk of cancer in IBD according to drug exposure and age. Danish national registers were used to identify incident IBD patients, exposure to drugs and status of cancers, in 1996-2018. Cox regressions were used to i) compare IBD to non-IBD reference individuals, ii) analyse IBD according to drug exposure status, and iii) assess patients’ cumulative drug exposure and the association to first reported cancer, excluding non-melanoma skin cancer.

Results

In total, 43,419 IBD patients were followed for a median of 8.2 years (IQR:3.7-14.2) after IBD diagnosis. Cancer was reported in 3,128 (7.2%) IBD patients. Both monotherapy and combination therapy were associated with developing cancer (aHR:1.36 (95%CI:1.17-1.58) and (aHR:2.48 (95%CI:1.64-3.76), respectively) compared to unexposed IBD patients. Among the elderly (>65 years), the risk was especially high in those receiving combination therapy. In patients who discontinued thiopurines, the aHR returned to the level of unexposed patients (aHR:0.89 (95%CI:0.78-1.01)). The aHR was positively associated with cumulative thiopurine exposure and in patients with more than five years of exposure, reaching aHR of 1.36 (95%CI:1.14-1.61).

Conclusion

Thiopurines were associated with increased risk of cancer, especially when used in combination therapy in the elderly. The risk increased by 36% when patients were exposed to thiopurines for more than five years. Reassuringly, the risk returned to baseline after discontinuation of thiopurines. This study suggests avoiding combination therapy in the elderly and not treating patients with thiopurines for longer than five years, regardless of age.

Disclosure

This study was funded by an unrestricted grant from Aage og Johanne Louis-Hansens Fond.

Introduction

Whereas there is an emerging consensus on the optimal approach to initiation of a range of therapies in inflammatory bowel disease (IBD), there remains greater uncertainty about the risks, benefits, and timing of stopping treatment when patients are in stable remission on therapy. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs.

Aims & Methods

Our study evaluated the risks of disease relapse associated with withdrawal of the biologic therapy in both ulcerative colitis (UC) and Crohn’s disease (CD). In this is a retrospective observational study, the exit strategy was proposed to 60 patients regularly followed in two IBD referral centre from 2015 to 2023. The exit startegy was performed as: (i) discontinuation without de-escalation, (ii) progressive de-escalation and (iii) azathioprine as monotherapy. Data on medical history were collected from electronic health records. Chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of disease relapse after the withdrawal.

Results

60 IBD patients were enrolled, 46 patients withdrawal their biologic therapy and 14 patients were in a de-escalation stategy. These 46 patients (15 UC and 31 CD) performed discontinuation without de-escalation (65%), progressive de-escalation (26%) and azathioprine as monotherapy (9%). They withdraw anti-TNF (82%) or other biologics (18%). Most of patients (71%) were on first line of biologic therapy. The median follow-up period after drug withdrawal was 29 months. A disease relapse occurred in 14 patiens with a median period of 12 months. A good recapture of previous therapy was observed in 57% of patients. Logistic regression analysis revealed a trend of significance between biologic therapy duration (p 0.05) and absence of flare-up after exit strategy. No correlation was noticed with duration of endoscopic or clinical remission before starting the drug withdrawal.

Conclusion

There are no specific factors related to a successful exit strategy. Biologic drug discontinuation is something best considered on a case-by-case basis and determined by patient preferences and disease features. We need more specific study in order to identify patients who can stop therapy without undue risk of poor outcomes.

Introduction

Azathioprine and mercaptopurine are commonly used to treat Inflammatory Bowel Disease (IBD), with around 6 in 10 patients being prescribed them at some point. Adherence to treatment is important to maintain disease control, prevent flare ups, reduce the need for steroids and improve wellbeing. A good response to treatment may delay or negate the need to escalate treatment to Biologic medications or surgery. Despite this, treatment non-adherence is a common problem among patients with chronic diseases, averaging at around 50%. In IBD specifically, the data varies widely, but non-adherence to oral therapy has been reported to be as high as 72%.

Aims & Methods

The aim of this study was to determine the adherence to azathioprine and mercaptopurine in IBD patients across the Bristol, North Somerset, South Gloucestershire Integrated Care Board (BNSSG ICB). Primary care records were searched to identify all patients with IBD prescribed azathioprine or mercaptopurine. Demographic data as well as data on disease type, length of treatment and co-prescription with a Biologic treatment was collected. Medication adherence was determined by GP records of pharmacy refill data.

Results

A total of 1313 patients were identified as having IBD and a current prescription for azathioprine or mercaptopurine, from 78 GP surgeries (98% of surgeries within the BNSSG ICB). 154 patients were excluded as they had been on azathioprine for less than 1 year. 59% of the 1159 included patients had Crohn’s disease. 360 patients (31%) were on combination therapy with a Biologic medication. 324 patients (28%) were found to be non-adherent with their medication based on prescription refill data suggesting that they do not have an adequate supply of medication.

Conclusion

Our data suggests that adherence to the immunosuppressant medications azathioprine and mercaptopurine in patients with IBD is comparable or slightly better than in other chronic diseases. However, pharmacy refill data is an indirect measure of medication adherence so adherence may have been overestimated. There remains a substantial proportion of patients who are not adhering to treatment, which is likely to be associated with poorer outcomes.

References

Chan W, Chen A, Tiao D, et al. Medication adherence in inflammatory bowel disease. Intest Res. 2017 Oct;15(4):434-445

Disclosure

No conflicts of interest to declare.