Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Infection with SARS-CoV-2 as a potential achalasia trigger.

Idiopathic achalasia is a chronic oesophageal motility disorder caused by loss of inhibitory neurons at the esophageal myenteric plexus resulting in incomplete relaxation of the lower oesophageal sphincter and abnormal peristaltism.  Among the possible causes of this, an immune response secondary to infection by some viruses has been implicated. SARS-CoV-2 could be considered among them. The therapy option should be aimed at achieving the greatest clinical effectiveness according to each patient's health status.

Enfermedad de Crohn perianal: implicaciones clínicas, pronósticas y consumo de recursos / Perianal Crohn's disease: clinical implications, prognosis and use of resources

Objetivo: conocer la prevalencia de la enfermedad perianal, los factores fenotípicos asociados, su influencia sobre el pronóstico y el impacto en el uso de recursos sanitarios en los pacientes con enfermedad de Crohn.Métodos: estudio observacional retrospectivo unicéntrico en el que incluimos 430 pacientes con enfermedad de Crohn en seguimiento en una consulta monográfica de enfermedad inflamatoria intestinal. Analizamos datos demográficos y fenotípicos de la enfermedad de Crohn, tratamientos farmacológicos y quirúrgicos, pruebas complementarias realizadas e ingresos hospitalarios, realizando estudio comparativo entre los pacientes sin enfermedad perianal y con enfermedad perianal, así como entre las formas simples y complejas.Resultados: la prevalencia de la enfermedad perianal fue del 40,2 % y sus manifestaciones más frecuentes fueron fístulas y abscesos. Su presencia se asoció a la afectación rectal y la existencia de manifestaciones extraintestinales. Los pacientes con enfermedad perianal precisaron con más frecuencia tratamiento inmunosupresor y biológico e ingresos, pero no más cirugía abdominal. Entre los pacientes con enfermedad perianal también fue más frecuente la necesidad de biológicos por la enfermedad luminal (42,8 % vs. 30,7 %). Además, condicionó un mayor consumo de exploraciones dirigidas al estudio de la enfermedad perianal y recto colonoscopias, pero no de entero-resonancia magnética (entero-RM)/entero-tomografía axial computarizada (entero-TAC).Conclusiones: la enfermedad perianal tiene una alta prevalencia en los pacientes con enfermedad de Crohn, sobre todo cuando existe afectación rectal. Se asocia a un peor pronóstico y requiere con más frecuencia tratamientos biológicos tanto por la evolución perianal como luminal, especialmente en la enfermedad perianal compleja. Esto condiciona más necesidad de ingresos hospitalarios y realización de exploraciones complementarias. (AU)

Ustekinumab en la enfermedad de Crohn: resultados en la vida real y posibles factores de respuesta / Ustekinumab in Crohn's disease: real-world outcomes and predictors of response

Antecedentes: ustekinumab es un anticuerpo monoclonal que inhibe las interleucinas IL-12 e IL-23, y está aprobado para el tratamiento de la enfermedad de Crohn (EC) y, más recientemente, también de la colitis ulcerosa (CU). El objetivo de este estudio fue evaluar la eficacia y seguridad de ustekinumab, así como identificar posibles factores predictivos de respuesta en un entorno de la vida real.Métodos: se realizó un estudio observacional, retrospectivo y multicéntrico en 4 hospitales de Andalucía. Se incluyeron pacientes adultos con diagnóstico confirmado de EC tratados con ustekinumab entre 2017 y 2019. Se analizó la respuesta clínica a los 3, 6 y 12 meses de tratamiento. La actividad clínica de la enfermedad se evaluó con el índice de Harvey-Bradshaw (HBI) y el índice de actividad de la enfermedad de Crohn (CDAI); La respuesta bioquímica se evaluó con parámetros de laboratorio como CRP y ESR. Se analizó la supervivencia al fármaco ustekinumab a un año.Resultados: Se analizaron un total de 98 pacientes (edad media, 43 años; el 52 % eran hombres); El 56 % había fracasado con ≥ 2 terapias biológicas previas. A los 3 meses, el 69 % de los pacientes estaban en respuesta y el 40,8 % en remisión. A los 6 meses, el 56 % estaba en remisión clínica. A los 12 meses, el 73,7 % estaba en respuesta clínica y el 60,5 % en remisión. La remisión sin corticosteroides fue del 32,4 %, 44 % y 47,4 % a los 3, 6 y 12 meses, respectivamente. La supervivencia acumulada tras un año de tratamiento con ustekinumab fue del 85,3 %. Los parámetros bioquímicos como CRP y ESR mostraron una disminución estadísticamente significativa entre los niveles de referencia y de control a los 3, 6 y 12 meses. Un HBI más bajo al inicio y el sexo femenino fueron predictores de remisión clínica libre de corticosteroides en un análisis univariante. (AU)

Impact of Epstein-Barr virus infection on inflammatory bowel disease (IBD) clinical outcomes.

OBJECTIVE: to evaluate the role of Epstein-Barr virus (EBV) on the intestinal mucosa in the evolution of inflammatory bowel disease (IBD). The risk factors for EBV infection and the frequency of EBV-associated lymphoproliferative disorders in IBD patients were also investigated. METHODS: intestinal biopsies of IBD patients with available EBV status determined by Epstein-Barr-encoding RNA (EBER) in situ hybridization were identified in the Pathology Database of our center. Clinical information, including phenotypic characteristics of IBD, previous treatments, diagnosis of lymphoma and patient outcome were reviewed in all cases. RESULTS: fifty-six patients with IBD (28 Crohn's disease, 27 ulcerative colitis and one unclassified colitis) were included. EBV in intestinal mucosa was positive in 26 patients (46 %) and was associated to a lymphoproliferative syndrome in one case. EBV positivity was associated with severe histological activity (52 % vs 17.2 %; p 0.007), the presence of a lymphoplasmacytic infiltrate (50 % vs 33.3 %; p 0.03) and active steroid treatment (61.5 % vs 33.3 %; p 0.03). Multivariate analyses only found an association between EBV and lymphoplasmacytosis (p 0.001). Escalation in previous treatment was significantly more frequent in the EBER+ group (53.8 % vs 26.7 %; p 0.038). No cases developed lymphoma during follow-up. CONCLUSIONS: EBV on the intestinal mucosa is associated with a poor outcome of IBD and the need for escalation of therapy. Lymphoplasmacytic infiltrate is associated with EBV infection. EBER+ patients used steroids more frequently compared with EBER- patients. No EBER+ patients developed lymphoma during follow-up.

Perianal Crohn's disease: clinical implications, prognosis and use of resources.

OBJECTIVE: to investigate the prevalence of perianal disease, the associated phenotypical factors, its influence on prognosis and its impact on the use of health resources for patients with Crohn's disease. METHODS: a unicentric retrospective observational study was performed with 430 patients with Crohn's disease tracked through a monographical consultation of intestinal inflammatory disease. Demographic and phenotypical data of Crohn's disease, pharmacological and surgical treatments, complementary tests carried out and hospital admissions were analyzed. A comparative study between those patients without perianal disease and those with perianal disease was performed, both in simple form and complex form. RESULTS: the prevalence of perianal disease was 40.2 %, and fistulas and abscesses were the most frequent manifestations. These appearances were associated with an affected rectum and the existence of extra-intestinal manifestations. The patients with perianal disease most frequently required immuno-suppressant and biological treatment, but no further abdominal surgery. Amongst the patients with perianal disease, the need for biologics was more frequent for luminal disease (42.8 % vs 30.7 %). Furthermore, more explorations were needed, aimed at the study of perianal disease and recto-colonoscopies, although more magnetic resonance (MR)/computed tomography (CT) enterographies were not required. CONCLUSIONS: perianal disease has a high prevalence among patients with Crohn's disease, especially when the rectum is affected. It is associated with a worse prognosis and more frequently requires biological treatments due to perianal and luminal evolution, especially in cases of complex perianal disease. This condition calls for more hospital admissions and complementary tests.

Ustekinumab in Crohn's disease: real-world outcomes and predictors of response.

BACKGROUND: ustekinumab is a monoclonal antibody that inhibits interleukins IL-12 and IL-23, and is approved for the treatment of Crohn's disease (CD) and, more recently, also ulcerative colitis (UC). The aim of this study was to evaluate the effectiveness and safety of ustekinumab, as well as to identify possible predictive factors of response in a real-life setting. METHODS: an observational, retrospective, multicenter study was carried out in 4 hospitals in Andalusia. Adult patients with a confirmed diagnosis of CD treated with ustekinumab from 2017 to 2019 were included. Clinical response was analyzed at 3, 6 and 12 months of treatment. Clinical disease activity was assessed with the Harvey-Bradshaw index (HBI) and the Crohn's Disease Activity Index (CDAI); biochemical response was assessed with lab parameters such as CRP and ESR. One-year ustekinumab drug-survival was analyzed. RESULTS: a total of 98 patients were analyzed (mean age, 43 years; 52 % were male); 56 % had failed with ≥ 2 previous biologicals therapies. At 3 months, 69 % of the patients were in response and 40.8 % in remission. At 6 months, 56 % were in clinical remission. At 12 months, 73.7 % were in clinical response and 60.5 % in remission. Corticosteroid-free remission was 32.4 %, 44 %, and 47.4 % at 3, 6, and 12 months, respectively. Cumulative survival after one year of treatment with ustekinumab was 85.3 %. Biochemical parameters such as CRP and ESR showed a statistically significant decrease between baseline and control levels at 3, 6, and 12 months. A lower HBI at baseline and female sex were predictors of corticosteroid-free clinical remission in a univariate analysis. In the multivariate analysis no variables were found as predictors of corticosteroid-free clinical remission. CONCLUSION: ustekinumab therapy is safe and useful, inducing clinical response in more than 50 % of patients, including patients who failed with other biological therapies.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Clinical outcome after anti-tumour necrosis factor therapy discontinuation in 1000 patients with inflammatory bowel disease: the EVODIS long-term study.

BACKGROUND: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. AIMS: To assess the risk of relapse in the long-term after anti-TNF discontinuation. METHODS: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. RESULTS: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. CONCLUSIONS: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Severe enterocolitis secondary to ipilimumab and nivolumab with an excellent response to a single dose of infliximab.

Immunotherapy is gaining significance in the management of oncological disease. It has demonstrated high levels of efficacy, though it also has hitherto unknown side effects, such as colitis. We present the first case of immune checkpoint inhibitor colitis (nivolumab+ipilimumab) refractory to corticoids treated in our hospital.

Megacolon en la enfermedad inflamatoria intestinal: respuesta a infliximab / No disponible

El megacolon es una complicación grave de la enfermedad inflamatoria intestinal que con frecuencia requiere colectomía. Infliximab sería una alternativa terapéutica cuando fracasa el tratamiento convencional, antes de la cirugía. En la actualidad, su uso se basa en la publicación de casos aislados. Presentamos nuestra serie de 12 pacientes con megacolon (cinco con signos de toxicidad sistémica) tratados con infliximab. El 75% de los pacientes evitaron la colectomía durante el episodio agudo tras la instauración precoz del tratamiento con infliximab (2,45 días desde el diagnóstico del megacolon), apreciando un mayor riesgo de cirugía entre los pacientes con colitis ulcerosa y criterios de toxicidad. Pese a mantener infliximab a largo plazo, dos pacientes más requirieron cirugía en el seguimiento. Ningún paciente sufrió efectos adversos relevantes en relación con el tratamiento ni complicaciones posquirúrgicas significativas

No disponible

Megacolon in inflammatory bowel disease: response to infliximab.

Megacolon is a serious complication of inflammatory bowel disease that often requires a colectomy. Infliximab is a therapeutic alternative when conventional treatment fails, before resorting to surgery. Its use is currently based on the publication of isolated cases. We present a series of 12 patients with megacolon treated with infliximab, five with signs of systemic toxicity. Seventy-five percent of the patients avoided a colectomy during their acute episode after early infliximab treatment, 2.45 days after the megacolon diagnosis. There was a greater risk of surgery among patients with ulcerative colitis and toxicity criteria. Two more patients required follow-up surgery despite long-term infliximab treatment. No patient suffered significant treatment-related adverse effects or significant post-surgery complications.

Granulocyte-monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis.

Objective: To evaluate the effectiveness and safety of the combination of granulocyte-monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC). Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy. Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique. Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

Mesalazina administrada de forma tópica como causa de síndrome de Stevens-Johnson / Topical mesalazine as a cause of Stevens-Johnson syndrome

La mesalazina es un fármaco usado habitualmente en la colitis ulcerosa que suele cursar con pocos efectos secundarios. Se han descrito casos infrecuentes de lesiones mucocutáneas graves como el síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET) secundarias a salicilatos. Es importante su diagnóstico precoz por su alta morbimortalidad. Presentamos el caso de una mujer de 46 años con proctitis ulcerosa que desarrolló un SSJ tras la administración tópica de mesalazina. La evolución de las lesiones fue favorable tras la suspensión del fármaco e inicio de corticoides intravenosos

Mesalazine is a drug routinely used in ulcerative colitis and usually has few side effects. There have been reports of uncommon cases of severe mucocutaneous damage, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), induced by salicylates. It is important to diagnose these promptly due to the high morbidity and mortality rates. We describe the case of a 46-year-old female with ulcerative proctitis, who developed SJS following topical mesalazine use. The lesions responded well to intravenous corticosteroids after discontinuation of the drug

Crohn's disease and cystic fibrosis: there is still a lot to learn.

The relationship between cystic fibrosis (CF) and the risk of developing inflammatory bowel disease (IBD) is not clear. CFTR mutations can influence dysbiosis and increased intestinal permeability, which are two key elements in the pathophysiology of IBD. These patients have increased intestinal inflammation, as demonstrated by increase pro-inflammatory gene expression in the bowel, specific fecal markers (fecal calprotectin), gross lesions (capsule endoscopy) and histological lesions on examination of surgical specimens.