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.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Memory T Cell Subpopulations as Early Predictors of Remission to Vedolizumab in Ulcerative Colitis.

Background: Vedolizumab is a humanized monoclonal antibody targeting the α4ß7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4+ and CD8+ memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis. Methods: Prospective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin <250 mcg/g or Mayo endoscopic subscore ≤1. Results: At week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α4ß7 + memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α4ß7 + memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction. Conclusion: CD8+ α4ß7 + memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders.

Re-induction With Intravenous Ustekinumab in Patients With Crohn's Disease and a Loss of Response to This Therapy.

BACKGROUND: A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn's disease who have lost the response to the treatment. METHODS: This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. RESULTS: Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. CONCLUSION: Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn's disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.

Uso de la cápsula endoscópica en enfermedad inflamatoria intestinal en práctica clínica en España. Resultados de una encuesta nacional / Use of capsule endoscopy in inflammatory bowel disease in clinical practice in Spain. Results from a national survey

Introducción: La cápsula endoscópica de intestino delgado (CEID) es una técnica diagnóstica poco invasiva cuyo empleo en la enfermedad inflamatoria intestinal (EII) se ha extendido. Se ha desarrollado recientemente una cápsula panentérica, PillCamCrohn's (PCC). Carecemos de información sobre la disponibilidad y el uso de la CEID y la PCC en nuestro medio. Métodos: Realizamos una encuesta electrónica y anónima entre los miembros del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa y la Asociación Española de Gastroenterología consistente en 37 preguntas de respuesta múltiple. Resultados: Participaron 150 miembros, la mayoría con dedicación especial a la EII (69,3%). El 72,8% trabajaban en centros con unidad de EII. El 79% tenían la CEID disponible en su hospital, y el 14% la derivaban a otro centro. El 22% tenían disponible la PCC, y el 9% la derivaban a otro centro. El 79,3% de encuestados con CEID disponible la utilizaban en un pequeño porcentaje de pacientes con EII y el 15,6% en la mayoría. Los escenarios más frecuentes fueron la sospecha de enfermedad de Crohn (76,3%), la valoración de actividad inflamatoria (54,7%) y la evaluación de la extensión de la enfermedad (54,7%). Más de la mitad (59,7%) utilizaban preferentemente la cápsula Patency® para valoración de la permeabilidad intestinal. Casi todos los encuestados (99,3%) consideraban que se deberían implementar recursos formativos en esta técnica. Conclusiones: La CEID cuenta con una amplia disponibilidad en los hospitales españoles para el manejo de la EII, si bien su uso es todavía limitado. Existe una oportunidad para aumentar la formación en esta técnica, y, con ella, su empleo.(AU)

Introduction: Small bowel capsule endoscopy (SBCE) is a non-invasive diagnostic technique whose use in inflammatory bowel disease (IBD) has spread. A panenteric capsule, PillCam Crohn's (PCC), has recently been developed. We lack information on the availability and use of the CEID and PCC in our environment. Methods: We conducted an electronic and anonymous survey among the members of the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) [Spanish Working Group on Crohn's Disease and Ulcerative Colitis] and the Asociación Española de Gastroenterología (AEG) [Spanish Association of Gastroenterology], consisting of 37 multiple-choice questions. Results: One hundred and fifty members participated, the majority dedicated to IBD (69.3%). 72.8% worked at centres with an IBD unit. 79% had SBCE available at their hospital, 14% referred patients to another centre; 22% had a PCC available, 9% referred patients to another centre. 79.3% of respondents with available SBCE used it in a small percentage of patients with IBD and 15.6% in the majority. The most frequent scenarios were suspicion of Crohn's disease (76.3%), assessment of inflammatory activity (54.7%) and assessment of the extent of the disease (54.7%). More than half (59.7%) preferentially used the Patency capsule to assess intestinal patency. Almost all respondents (99.3%) considered that training resources should be implemented in this technique. Conclusions: SBCE is widely available in Spanish hospitals for the management of IBD, although its use is still limited. There is an opportunity to increase training in this technique, and consequently its use.(AU)

Use of capsule endoscopy in inflammatory bowel disease in clinical practice in Spain. Results from a national survey. / Uso de la cápsula endoscópica en enfermedad inflamatoria intestinal en práctica clínica en España. Resultados de una encuesta nacional.

INTRODUCTION: Small bowel capsule endoscopy (SBCE) is a non-invasive diagnostic technique whose use in inflammatory bowel disease (IBD) has spread. A panenteric capsule, PillCam Crohn's (PCC), has recently been developed. We lack information on the availability and use of the CEID and PCC in our environment. METHODS: We conducted an electronic and anonymous survey among the members of the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) [Spanish Working Group on Crohn's Disease and Ulcerative Colitis] and the Asociación Española de Gastroenterología (AEG) [Spanish Association of Gastroenterology], consisting of 37 multiple-choice questions. RESULTS: One hundred and fifty members participated, the majority dedicated to IBD (69.3%). 72.8% worked at centres with an IBD unit. 79% had SBCE available at their hospital, 14% referred patients to another centre; 22% had a PCC available, 9% referred patients to another centre. 79.3% of respondents with available SBCE used it in a small percentage of patients with IBD and 15.6% in the majority. The most frequent scenarios were suspicion of Crohn's disease (76.3%), assessment of inflammatory activity (54.7%) and assessment of the extent of the disease (54.7%). More than half (59.7%) preferentially used the Patency capsule to assess intestinal patency. Almost all respondents (99.3%) considered that training resources should be implemented in this technique. CONCLUSIONS: SBCE is widely available in Spanish hospitals for the management of IBD, although its use is still limited. There is an opportunity to increase training in this technique, and consequently its use.

Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry.

BACKGROUND AND AIMS: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. METHODS: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. RESULTS: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. CONCLUSIONS: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Effectiveness and safety of methotrexate monotherapy in patients with Crohn's disease refractory to anti-TNF-α: results from the ENEIDA registry.

BACKGROUND: Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited. AIM: To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs. METHODS: A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded. RESULTS: Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation. CONCLUSIONS: The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease.

BACKGROUND: Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD). AIMS: To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice. METHODS: We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment. RESULTS: One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs <10 ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3 months. Of 62 patients with perianal disease, complete closure was observed in 8% (n = 5) of patients with perianal fistulas, with 34% (n = 21) showing partial response. Treatment was maintained for a median of 6 months (IQR, 2-16). After a median clinical follow-up of 24 months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P = 0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC. CONCLUSIONS: Tacrolimus shows a clinical benefit in both CD and UC after 3 months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.

Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn's disease.

BACKGROUND: Identifying predictors of therapeutic response is the cornerstone of personalized medicine. AIM: To identify predictors of long-term mucosal healing (MH) in patients with Crohn's disease (CD) treated with tumor necrosis factor α (TNF-α) inhibitors. METHODS: Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity (CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response (ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments. RESULTS: Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment (53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52% and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46 (59% sensitivity and 91% specificity; area under the curve = 0.778). CONCLUSION: Clinical and biomarker data are not useful predictors of response to TNF-α inhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-α therapy.

Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.

BACKGROUND AND AIMS: Recent studies have shown the efficacy of autologous haematopoietic stem cell transplantation [HSCT] in severely refractory Crohn's disease [CD] patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. METHODS: We followed a group of CD patients [n = 18] receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanisms driving efficacy, we monitored changes after HSCT in blood and intestine immune-cell composition. CD patients [n = 22] receiving anti-tumour necrosis factor [TNF]-α were included for comparison. RESULTS: Severe immune ablation followed by HSCT induced dramatic changes in both peripheral blood T and B cells in all patients regardless of the efficacy of the treatment. Endoscopic remission at week 52 following HSCT was associated with significant intestinal transcriptional changes. A comparison of the remission signature with that of anti-TNFα identified both common and unique genes in the HSCT-induced response. Based on deconvolution analysis of intestinal biopsy transcriptome data, we show that response to HSCT, but not to anti-TNFα, is associated with an expansion of naïve B-cells, as seen in blood, and a decrease in the memory resting T-cell content. As expected, endoscopic remission, in response to both HSCT and anti-TNFα, led to a significant reduction in intestinal neutrophil and M1 macrophage content. CONCLUSIONS: Peripheral blood immune remodelling after HSCT does not predict efficacy. In contrast, a profound intestinal T-cell depletion that is maintained long after transplant is associated with mucosal healing following HSCT, but not anti-TNFα.

Autologous Haematopoietic Stem Cell Transplantation for Refractory Crohn's Disease: Efficacy in a Single-Centre Cohort.

BACKGROUND: Haematopoietic stem cell transplantation [HSCT] is considered a therapeutic option for patients with severe Crohn's disease [CD] unresponsive to currently available therapies. METHODS: Autologous HSCT was considered for CD patients with active disease, unresponsive or intolerant to approved medications and unsuitable for surgery. After HSCT, patients were closely followed up every 6 weeks during the first 2 years and every 6 months thereafter up to 5 years. Colonoscopy and/or magnetic resonance imaging were performed at Months 6, 12, 24, and 48 after HSCT. RESULTS: From December 1, 2007 to December 31, 2015, 37 CD patients were assessed for HSCT. Of these, 35 patients [13 within the ASTIC trial] underwent mobilisation. Six patients did not complete the transplant for various reasons and 29 patients were finally transplanted. Patients were followed up during a median of 12 months [6-60]. At 6 months, 70% of patients achieved drug-free clinical remission (Crohn's Disease Index of Severity [CDAI] < 150). The proportion of patients in drug-free remission (CDAI < 150, Simple Endoscopic activity Score [SES]-CD < 7] was 61% at 1 year, 52% at 2 years, 47% at 3 years, 39% at 4 years, and 15% at 5 years. Patients who relapsed were re-treated and 80% regained clinical remission. Six out of the 29 [21%] required surgery. One patient died due to systemic cytomegalovirus infection 2 months after transplant. CONCLUSIONS: HSCT is a salvage therapy for patients with extensive and refractory CD. Although relapse occurs in a majority of patients within 5 years after transplant, drug responsiveness is regained and clinical remission achieved in 80% of cases.

Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients.

BACKGROUND: Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA. METHODS: This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response. RESULTS: We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission. CONCLUSIONS: In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.