In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn’s disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. Results Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P = 0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P = 0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P = 0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P = 0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. Conclusions Patients with moderate-to-severe Crohn’s disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)

/pdf/infliximab-azathioprine-or-combination-therapy-for-crohn-s-hjetjoy88b.pdf

Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

https://gut.bmj.com/content/gutjnl/66/1/6.full.pdf

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

BACKGROUND: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2007.03562.x

Review article: the role of butyrate on colonic function

BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1602773/suppl_file/nejmoa1602773_appendix.pdf

Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease

[Crohn's disease].

EMA response to ECCO position statement on biosimilars.

Antecedentes: El objetivo de este estudio fue estimar los costes directos hospitalarios asociados al manejo clinico y terapeutico de los pacientes con enfermedad de Crohn moderada y grave en la practica clinica habitual en Espana. Metodologia: Estudio descriptivo, naturalistico, retrospectivo, de caracter multicentrico y de ambito nacional. Participaron en el estudio 10 medicos gastroenterologos de 10 hospitales espanoles. La informacion para el estudio se obtuvo de una revision de historias clinicas de pacientes con enfermedad de Crohn (EC). Se elaboro un modelo de Markov para estimar el coste directo sanitario por paciente asociado al manejo clinico y terapeutico de la enfermedad de Crohn, desde la perspectiva del Sistema Nacional de Salud (SNS) en un periodo de tres anos. Se ha realizado un analisis de sensibilidad para evaluar el impacto en los resultados de cambios en las principales variables. Resultados: Se incluyo a 178 pacientes. La estimacion del coste directo sanitario asociado a la EC para un periodo de 3 anos fue de 23.168 € por paciente (7.722 € por paciente y ano). Los ingresos hospitalarios representaron un 57% del total de los costes asociados a la EC, los costes asociados al tratamiento farmacologico el 33% (27% debido a terapias biologicas (TB) y 6% por terapias convencionales). Los demas costes que incluyen visitas, pruebas e intervenciones quirurgicas representaron un 10%. La probabilidad de recibir terapia biologica fue la unica variable testada que presento un impacto significativo en el resultado final del modelo. Conclusiones: El coste directo de la EC se debe en su mayor parte a los ingresos hospitalarios y a la intensa utilizacion de recursos en los estados mas graves de la enfermedad. La utilizacion de mayores dosis de TB en la practica clinica habitual, en comparacion con las de sus fichas tecnicas, esta directamente relacionada con el aumento de los costes de la EC.

Costes médicos directos de la enfermedad de Crohn en España

Budesonide and inflammatory bowel disease

Azathioprine is currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that inflammatory bowel diseases are to date chronic, non-curable conditions, treatment should be indefinite and only the loss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous usefulness of the drug in the long term: in fact its withdrawal very substantially increases the risk of relapse. About side effects, azathioprine is a relatively well tolerated drug and even indefinite use seems safe. The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug. Recent metanalysis suggests that the risk of lymphoma is real, but the individual risk is rather low, and decision analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in patients with inflammatory bowel diseases in whom azathioprine is effective and well tolerated, the drug should not be stopped. This recommendation concerns the use of azathioprine as a single maintenance drug, and is not necessarily applicable to patients receiving concomitant biological therapy.

Fernando Gomollón

Papers

EMA response to ECCO position statement on biosimilars.

Costes médicos directos de la enfermedad de Crohn en España

Budesonide and inflammatory bowel disease

Are we giving azathioprine too much time

The GETECCU clinical guideline for the treatment of ulcerative colitis:: A guideline created using GRADE methodology