Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.

The availability of biologic therapies in inflammatory bowel disease (IBD) is increasing significantly. This represents more options to treat patients, but also more difficulties in choosing the therapies, especially in the context of bio-naïve patients. Most evidence of safety and efficacy came from clinical trials comparing biologics with placebo, with a lack of head-to-head studies. Network meta-analysis of biologics and real-world studies have been developed to solve this problem. Despite the results of these studies, there are also other important factors to consider before choosing the biologic, such as patient preferences, comorbidities, genetics, and inflammatory markers. Given that resources are limited, another important aspect is the cost of biologic therapy, since biosimilars are widely available and have been demonstrated to be effective with a significant decrease in costs. In this review, we summarize the evidence comparing biologic therapy in both Crohn´s disease (CD) and ulcerative colitis (UC) in different clinical situations. We also briefly synthesize the evidence related to predictors of biologic response, as well as the biologic use in extraintestinal manifestations and the importance of the drug-related costs.

Inflammatory bowel diseases (IBDs) are associated with an increased risk of metabolic comorbidities. There is a lack of data regarding the relationship between lifestyle and metabolic diseases in IBD patients. A cross-sectional study on consecutive IBD outpatients was conducted. Adherence to the Mediterranean diet (MD) was assessed using a 14-item questionnaire from the PREDIMED study, and physical activity was evaluated using the GODIN-Leisure score. Body composition was studied based on body mass index and waist–hip ratio (WHR), while quality of life was assessed using a nine-item short questionnaire. Among the 688 evaluated IBD patients, 66% were overweight or obese, 72.7% did not lead an active lifestyle and 70.1% did not adhere to the MD. Metabolic syndrome was associated with age (OR = 1.07, p = 0.019), overweight/obesity (OR = 12.987, p < 0.001) and the inflammatory behavior of Crohn’s disease (OR = 6.172, p = 0.001). Type 2 diabetes mellitus or prediabetes was associated with age (OR = 1.063 p = 0.016), overweight/obesity (OR = 3.861, p < 0.001) and the inflammatory behavior of Crohn’s disease (OR = 4.716, p = 0.001). Overweight /obesity (OR = 5.494, p < 0.001), a high WHR (OR = 2.564, p = 0.005) and a non-active lifestyle (OR = 2.202, p = 0.0003) were associated with metabolic dysfunction-associated steatotic liver disease. Lifestyle, body composition and not solely systemic inflammation might exert a significant influence on the emergence of metabolic comorbidities such as MASLD, type 2 diabetes mellitus and metabolic syndrome in patients with IBD.

Background: Management of Helicobacter pylori infection has been expanded from the gastroenterology specialist (GS) to primary care physicians (PCPs), with a large increase in requests for urea breath tests (UBT). Due to the lack of evidence at this level, we evaluated the appropriateness of UBT indications and treatment for H pylori infections between PCPs and GSs and the effect of introducing specific counseling to PCPs.Materials and Methods: This was a quasi‐experimental study. Phase I included 650 consecutive UBT requested by PCPs (400) and GSs (250). Indications and treatments were classified as appropriate or inappropriate based on national guidelines. Data on eradication rates were also collected. In phase II, 240 UBT and patients' treatment outcomes were analyzed after individually counseling PCPs on both aspects.Results: Of 1049 UBT, inappropriate indications in phase I were significantly higher in tests requested by PCP compared with GS (35.9% vs 7.2%; P < 0.001). Inappropriate treatment regimens were significantly higher for PCPs in phase I (65.8% vs 26.4%; P < 0.001). Consequently, eradication rates were significantly lower in patients treated by PCPs compared with those treated by GS (63.7% vs 81.4%; P = 0.004). A significant increase in adherence to appropriate treatment regimens (75.8% vs 34.2%; P < 0.001) and eradication rates (79.2% vs 63.7%; P = 0.002) were observed in the PCP group after counseling; however, the appropriateness of indications did not improve.Conclusions: Patients infected with H pylori managed at the primary care level had poorer outcomes. The introduction of specific counseling for PCPs significantly improved treatment management, but not indications.

The risk for gastrointestinal bleeding from dual antiplatelet therapy (DAPT) with new antiplatelets (prasugrel/ticagrelor) compared to clopidogrel is unclear. Aim: To determine the risk and type of major (gastrointestinal bleeding requiring hospitalization) and minor (anemia and iron deficiency) gastrointestinal events with different types of DAPT. Methods: Retrospective observational cohort study of patients who started DAPT after percutaneous coronary intervention. Follow-up was censored after 12 months of DAPT, when a major gastrointestinal event occurred, or when DAPT was discontinued. Results: Among 1,327 patients (54.03% were treated with clopidogrel-based DAPT, 38.13% with ticagrelor-based DAPT, and 7.84% with prasugrel-based DAPT), 29.5% had at least one gastrointestinal event. Patients taking clopidogrel-DAPT were older, with more comorbidities, and higher gastrointestinal risk compared to those taking other DAPT regimens. Adjusted hazard ratios (HRs) showed no between-group differences in the risk for major (clopidogrel vs. new antiplatelets: HR 0.996; 95% confidence interval 0.497–1.996) and minor (HR 0.920; 0.712–1.189) gastrointestinal events. Most patients received proton pump inhibitors while on DAPT (93.3%) and after withdrawal (83.2%). Conclusion: Prasugrel- or ticagrelor-based DAPT was not associated with increased gastrointestinal bleeding risk when compared to clopidogrel-DAPT. New antiplatelets do not necessarily need to be restricted to patients with low gastrointestinal risk.

Helicobacter pylori infection (H. pylori) is mainly managed at the primary care level. Our group previously performed a study demonstrating that providing specific counselling (SC) to primary care practitioners (PCPs) who requested a urea breath test (UBT) improved treatment management but not indications for H. pylori tests. SC was given in the form of a personal letter addressed to PCPs with UBT results which contained information about accepted UBT indications and a Helicobacter pylori treatment algorithm. The purpose of the present study was to evaluate the effect of training sessions (TS) on UBT indications, antibiotic prescriptions and eradication rates. This was a quasi-experimental study performed at primary care centres (PCCs). Phase I included 399 patients diagnosed with H. pylori infection after providing SC to PCPs. Phase II included 400 H. pylori-positive patients after giving TS to PCPs who had already received SC (100 from PCCs with TS and 300 from PCCs without TS). An improved trend in the appropriate indication of H. pylori diagnosis was observed between Phase I and PCCs with TS in Phase II (57.5% vs. 67%; p = 0.06). TS improved appropriate prescriptions in PCCs with TS compared to PCCs that only received SC in Phase I and II (94% vs. 75.3%, p = 0.01; 94% vs. 85.6%, p = 0.04, respectively). Eradication rates showed no differences between groups. In conclusion, training sessions after specific counselling improved antibiotic prescription appropriateness but not eradication rates.