Long-term clinical outcome after thiopurine discontinuation in elderly IBD patients.

INTRODUCTION AND AIM: Thiopurines - although used frequently in inflammatory bowel diseases (IBD) - carry a significant safety risk, particularly with prolonged use and/or in elderly patients. Stopping therapy, however, may trigger relapses. We assessed the long-term outcome of elderly IBD patients after discontinuation of thiopurine while in clinical remission. METHODS: Electronic medical records from IBD patients >60 years whoever received thiopurine treatment were reviewed. Patients who stopped thiopurine after 60 years of age while in clinical and/or endoscopic remission were included. Long-term outcomes included duration of clinical remission, time to clinical relapse, and development of malignancy. RESULTS: In total, 142 patients receiving thiopurines while they were >60 years were identified. Ninety-one patients stopped thiopurines at >60years while in clinical and/or endoscopic remission. After a median follow-up of 66 months, 28 (30.8%) developed a clinical relapse. The median duration of TP therapy in relapses was significantly shorter than in patients who remained in remission (median 45 vs. 103 months, respectively; p = .005). After relapse, 10 patients started a biological (36%) and seven received steroids (25%). Surgery was needed in 36% of patients (10/28). Overall, 26 malignancies developed. CONCLUSION: Discontinuation of TP in elderly IBD patients in clinical and/or endoscopic remission results in sustained clinical remission in two-thirds of patients. Patients who flare can mostly be rescued with biologicals although one-third necessitate surgery. A significant proportion of patients developed malignancies under but also after thiopurines discontinuation, indicating that these patients necessitate a continued close follow-up. Decision-making in this vulnerable subgroup of patients remains difficult.

Estrogen receptor ß controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage.

Injury to the enteric nervous system (ENS) can cause several gastrointestinal (GI) disorders including achalasia, irritable bowel syndrome, and gastroparesis. Recently, a subpopulation of enteric glial cells with neuronal stem/progenitor properties (ENSCs) has been identified in the adult ENS. ENSCs have the ability of reconstituting the enteric neuronal pool after damage of the myenteric plexus. Since the estrogen receptor ß (ERß) is expressed in enteric glial cells and neurons, we investigated whether a selective ERß agonist, LY3201, can influence neuronal and glial cell differentiation. Myenteric ganglia from the murine muscularis externa were isolated and cultured in either glial cell medium or neuronal medium. In glial cell medium, the number of glial progenitor cells (Sox10+) was increased by fourfold in the presence of LY3201. In the neuronal medium supplemented with an antimitotic agent to block glial cell proliferation, LY3201 elicited a 2.7-fold increase in the number of neurons (neurofilament+ or HuC/D+). In addition, the effect of LY3201 was evaluated in vivo in two murine models of enteric neuronal damage and loss, namely, high-fat diet and topical application of the cationic detergent benzalkonium chloride (BAC) on the intestinal serosa, respectively. In both models, treatment with LY3201 significantly increased the recovery of neurons after damage. Thus, LY3201 was able to stimulate glial-to-neuron cell differentiation in vitro and promoted neurogenesis in the damaged myenteric plexus in vivo. Overall, our study suggests that selective ERß agonists may represent a therapeutic tool to treat patients suffering from GI disorders, caused by excessive neuronal/glial cell damage.

There is no benefit in routinely monitoring ANCA titres in patients with granulomatosis with polyangiitis.

OBJECTIVES: To analyse the link between antineutrophil cytoplasmic antibody (ANCA) levels and risk of relapse in patients with granulomatosis with polyangiitis (GPA), as the clinical benefit of monitoring ANCA levels is uncertain. METHODS: A retrospective analysis was made of all charts available from 43 patients diagnosed with GPA, fulfilling The American College of Rheumatology 1990 criteria, and followed between 1994 and 2012 at a general internal medicine department of a university hospital. Clinical and biochemical data (i.e. anti-proteinase 3 (PR3) levels) were collected and correlated. RESULTS: 43 relapses occurred in 25 patients (58.1% of 43 patients). When blood samples are routinely taken at a follow-up visit (i.e. low pre-test probability, ± 5.5%) in the GPA-population, a 75%-increase in the PR3-level or its reappearance has only limited positive predictive value (PPV 15.0% and 22.5% respectively) for predicting relapse. Adversely, when clinical suspicion of relapse is high (i.e. high pre-test probability, for example 50%), an increase of 75% or reappearance of PR3 makes relapse even more likely (PPV 77.5%, 81.6% respectively). Conversely, a high negative predictive value (NPV) of 99.3% and a negative likelihood ratio (LR-) of 0.12 suggest that, in the absence of PR3, relapse is unlikely if patients had detectable ANCAs at diagnosis. CONCLUSIONS: Routine ANCA monitoring in patients diagnosed with GPA has limited value. However, targeted determination of ANCA levels may be useful if a relapse is clinically suspected (i.e. high pre-test probability).

Tofacitinib for celiac disease and microscopic colitis: killing two birds with one stone.

Microscopic colitis is a chronic inflammatory condition of the colon. Firstline treatment consists of budesonide, with the consideration of biological agents in refractory cases. Celiac disease is a chronic immune mediated and gluten-induced enteropathy, with treatment consisting of a gluten-free diet. There is an association between microscopic colitis and instead of xand celiac disease, especially in refractory cases they can coincide. In this manuscript, we report for the first time the efficacy of tofacitinib, a pan Janus kinase inhibitor, in the treatment of concomitant microscopic colitis and celiac disease, resulting in persistent clinical and histological remission.

Short- and Long-term Outcomes Following Side-to-side Strictureplasty and its Modification Over the Ileocaecal Valve for Extensive Crohn's Ileitis.

BACKGROUND AND AIMS: Postoperative recurrence remains a challenging problem in patients with Crohn's disease [CD]. To avoid development of short bowel syndrome, strictureplasty techniques have therefore been proposed. We evaluated short- and long-term outcomes of atypical strictureplasties in CD patients with extensive bowel involvement. METHODS: Side-to-side isoperistaltic strictureplasty [SSIS] was performed according to the Michelassi technique or modification of this over the ileocaecal valve [mSSIS]. Ninety-day postoperative morbidity was assessed using the comprehensive complication index [CCI]. Clinical recurrence was defined as symptomatic, endoscopically or radiologically confirmed, stricture/inflammatory lesion requiring medical treatment or surgery. Surgical recurrence was defined as the need for any surgical intervention. Endoscopic remission was defined as ≤i1, according to the modified Rutgeerts score. Deep remission was defined as the combination of endoscopic remission and absence of clinical symptoms. Perioperative factors related to clinical recurrence were evaluated. RESULTS: A total of 52 CD patients [SSIS n = 12; mSSIS n = 40] were included. No mortality occurred. Mean CCI was 10.3 [range 0-33.7]. Median follow-up was 5.9 years [range 0.8-9.9]. Clinical recurrence [19 patients] was 29.7% and 39.6% after 3 and 5 years, respectively. Surgical recurrence [seven patients] was 2% and 14.1% after 3 and 5 years, respectively. At the end of the follow-up, 92% of patients kept the original strictureplasty and deep remission was observed in 25.7% of the mSSIS patients. None of the perioperative variables considered showed a significant association with clinical recurrence. CONCLUSIONS: SSIS is safe, effective, and provides durable disease control in patients with extensive CD ileitis.