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Background Older age has been reported as a risk factor for severe SARS-CoV-2 disease (COVID-19). The impact of immunosuppressants (IMS) on COVID-19 is still under debate. Aim To describe the incidence and severity of COVID-19 in elderly patients with inflammatory bowel disease (IBD) in relation to the use of IMS. Methods IBD patients over 65 years of age were selected and grouped in terms of IMS use. Confirmed COVID-19, adherence to IST, comorbidities and concomitant non-IBD-related treatments between 1st of March 2020 to 1st of March 2021 were recorded. Results Out of 418 patients included, 89 (21.3%) were on IMS. Thirty-two patients (7.7%) had COVID-19, 7 of whom were on IMS (7.6% not on IMS vs. 7.9% on IMS; P = 0.933) and 7 (22%) patients died. Conclusions Incidence of COVID-19 among elderly IBD patients was similar to that reported in the background population, regardless of the use of IMS.

Background Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. Aims Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. Methods IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey‐Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. Results A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4–37.5). Conclusion Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Background: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. Methods: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adatimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). Results: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. Conclusions: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence. (C) 2019 Elsevier Espana, S.L.U. All rights reserved.

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

Background Older age has been confirmed as a risk factor for severe clinical presentation of SARS-CoV-2 disease (COVID-19). The prevalence of confirmed SARS-CoV-2 infection in Catalonia among people over 60 years is 6.6%. Biological agents have not been associated with a higher incidence nor a worse prognosis of COVID-19. However, the role of immunosuppressants (IMS) on this issue is still to be elucidated. Moreover, there are scarce data related about COVID-19 in inflammatory bowel disease (IBD) patients under IMS, and none focusing in elderly IBD. Our aim was to describe and to compare the incidence and severity of COVID-19 in patients over 65 years of age with IBD, particularly in relation to the use of IMS. Methods We performed a retrospective cohort study including IBD patients over 65 years since January 2020, from two referral centres in the Barcelona metropolitan area (Catalonia, Spain). Patients were grouped in two cohorts regarding the use or not of IMS (thiopurines or methotrexate). Patients on biological treatment were excluded. We identified those cases with confirmed infection with SARS-CoV-2 (positive PCR) during the period from 1st of March 2020 (the beginning of the pandemic in Catalonia) to 1st March 2021 (the beginning of vaccination in the elderly). Demographic data, IBD comorbidities, concomitant non-IBD related treatments, and SARS-CoV-2 infection outcomes were recorded. Results Four-hundred and eighteen elderly IBD patients were included. The median age was 74 years (IQR 69–78), 52% were male; 70% had ulcerative colitis, 28% Crohn’s disease and 2% IBD unclassified, 62% had arterial hypertension, 22% diabetes mellitus, 22% cardiovascular disease, 15% chronic obstructive pulmonary disease, 10% chronic renal disease, 5% were active smokers. There were no differences regarding comorbidities and non-IBD treatments between the two study groups. From the whole cohort, 89 (21.3%) patients were on IMS (86 with thiopurines, 3 with methotrexate). The median time on IMS was 121 months (IQR 60–162). During the study period, 32 patients (7.7%) had confirmed SARS-CoV-2 infection (7 of whom were on IST; 7.6% not on IMS vs. 7.9% on IMS, P=0.933). Seventeen (53%) patients required hospital admittance (4% not IMS vs. 4.5% on IMS; P=0.818); 4 of them developed COVID-19 related complications (3 patients not on IMS vs. 1 on IMS), and 7 (22%) patients died (6 not on IMS vs. 1 patient on IMS). Conclusion The rate of SARS-CoV-2 infection among elderly IBD patients is quite similar to that reported in the elderly background population. In elderly IBD patients, SARS-CoV-2 infection was associated with a high admission rate and mortality, regardless of the use of IMS.

Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Background/Objective: Evidence from basic and clinical studies suggests that unsaturated fatty acids (UFAs) might be relevant mediators of the development of complications in acute pancreatitis (AP). Objective: The aim of this study was to analyze outcomes in patients with AP from regions in Spain with different patterns of dietary fat intake. Materials and Methods: A retrospective analysis was performed with data from 1,655 patients with AP from a Spanish prospective cohort study and regional nutritional data from a Spanish cross-sectional study. Nutritional data considered in the study concern the total lipid consumption, detailing total saturated fatty acids, UFAs and monounsaturated fatty acids (MUFAs) consumption derived from regional data and not from the patient prospective cohort. Two multivariable analysis models were used: (1) a model with the Charlson comorbidity index, sex, alcoholic etiology, and recurrent AP; (2) a model that included these variables plus obesity. Results: In multivariable analysis, patients from regions with high UFA intake had a significantly increased frequency of local complications, persistent organ failure (POF), mortality, and moderate-to-severe disease in the model without obesity and a higher frequency of POF in the model with obesity. Patients from regions with high MUFA intake had significantly more local complications and moderate-to-severe disease; this significance remained for moderate-to-severe disease when obesity was added to the model. Conclusions: Differences in dietary fat patterns could be associated with different outcomes in AP, and dietary fat patterns may be a pre-morbid factor that determines the severity of AP. UFAs, and particulary MUFAs, may influence the pathogenesis of the severity of AP., GG-R was supported by grant from the Instituto de Salud Carlos III and Instituto de Investigación Sanitaria (IIS) Aragón [Río Hortega grant CM17/00145].

Background Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. Aims Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. Methods Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. Results The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease,p < 0.001), gender (female,p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. Conclusions One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment.Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50mg every 4weeks (q4wk) was optimized before week 14 to 100mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival.Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80kg were assigned to a golimumab maintenance dose of 50mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50mg q4wk were optimized to 100mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal.Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.

Background Mycophenolate mofetil (MMF) is an immunomodulatory drug that inhibits T and B cells, through a reversible inhibition of inositol monophosphate dehydrogenase. MMF is commonly used for prophylaxis of organ rejection after transplant. Studies to evaluate its use in inflammatory bowel disease (IBD) are limited especially after the appearance of biological treatments (BT). The aim of this study was to evaluate the efficacy and safety of MMF in IBD. Methods IBD patients who had received MMF were identified in the ENEIDA registry (prospective database of GETECCU). Patients with Crohn′s disease (CD) or Ulcerative colitis (UC) in whom oral MMF was prescribed for this condition were evaluated. Demographic and IBD clinical data were collected. Clinical activity was assessed through Harvey-Bradshaw Index (HBI) and partial Mayo score (pMS); C-reactive protein (CRP) and faecal calprotectin (FC) were reviewed at baseline (at MMF starting), 3 and 6 months and at the end of follow-up (at MMF stopping or the last visit while on MMF). Adverse events (AEs) during MMF treatment were documented. Statistical analyses were performed by descriptive statistics and non-parametric tests. Results Between June 1999 and November 2018 a total of 83 patients received MMF (mean age 36.4 (SD12.3) years; 52F/31M; 66 CD and 17 UC). Indication for MMF use was maintenance of remission (50%), induction of remission (44%) and post-surgical prophylaxis (6%). Mean MMF dose used was 1269.8 (SD 741) mg/day. In 61% of cases, systemic steroids were administered starting MMF and it was used concomitantly to BT in 27% of patients. In CD, statistically significant differences in HBI at 6 months (mean 5.9 (SD 4.8), p = 0.04) and at the end of follow-up (mean 5.7 (SD 5), p = 0.014) compared with baseline (mean 7.6 (SD 4.3)) were observed. In UC, statistically significant differences in pMS at 6 months (mean 2.1 (SD 2.7), p = 0.018) and at the end of follow-up (mean 1.8 (SD 2.6), p = 0.003) compared with baseline (mean 4.8 (SD 2.5)) were determined. No significant differences in CRP or CF values during follow-up were observed. Concomitant use of BT was significantly associated with clinical response (OR 1.36 95% CI 1.08–1.73). MMF was maintained for a median time of 28.9 months (IQR 20.4–37.5) and was stopped in 84% of patients due to lack of response (50%), loss of response (17%) and remission (15%). Overall, 23% of patients presented MMF-related AEs (60% abdominal pain). MMF was withdrawn in 11% of patients due to AEs. Conclusion MMFshows a clinical benefit in the long term in both CD and UC patients with a favourable safety profile. MMF could be a treatment option alone or in combination with biologics in patients with IBD in clinical practice.