Combination of granulocyte-monocyte apheresis and ustekinumab: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. PATIENTS AND METHODS: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. CONCLUSION: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

Assessment of the quality of life of patients with inflammatory bowel disease. / Evaluación de la calidad de vida de los pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Ulcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients' quality of life. The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL). MATERIAL AND METHODS: Observational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included. For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used. RESULTS: 106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission. The median questionnaire score was 60.8 points out of 100. Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not. A negative association was observed between the number of flares and the questionnaire score. CONCLUSIONS: In our study population, there is an acceptable HRQoL, with no differences observed between CD and UC. Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.

Assessment of the length of sick leave in patients with inflammatory bowel disease. / Evaluación de la duración de la baja laboral en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic disorder that can lead to periods of work-related temporary disability (TD), which may result in the need for permanent disability. The objective was to assess the impact of IBD on patients' temporary disability by analyzing periods, duration, and causes. It also investigates risk factors influencing the severity, frequency, and duration of flare-ups and associated complications in IBD patients. METHOD: The study includes patients aged 18 to 65, with at least 1 day of TD in 2019 (Pre-COVID), referred or not by UMEVI, due to reasons related to IBD. RESULTS: A total of 172 patients were included, and in all cases, TD was associated with IBD. TD was higher in patients over 30 years old, with anxious depressive disorder, who required hospitalization and did not receive prednisone treatment (p<0.05). TD duration was longer in patients belonging to the Special Regime for Self-Employed Workers (RETA): 67 days (IQR: 22-160) versus the General Regime (RG): 33 days (IQR: 8-110), with no statistically significant difference (p=0.120). The mean cost (€) per worker in this series was €745.5 (IQR: 231-2608.2). CONCLUSIONS: IBD has a significant impact on patients' temporary work disability. The duration of TD was longer in patients older than 30 years, with anxious-depressive disorder, who required hospital admission and did not receive steroid treatment.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Use of digital health tools in inflammatory bowel disease. / Uso de herramientas digitales en salud en enfermedad inflamatoria intestinal.

OBJECTIVE: To analyse the characteristics and use of digital health tools (DHT) in inflammatory bowel disease (IBD). METHODS: We performed a qualitative study based on a narrative literature review, a questionnaire and on the opinion of 3 expert gastroenterologists. Several searches were carried out until September 2022 through Medline to identify articles on the use of DHT in IBD by healthcare professionals. A structured questionnaire was designed to be answered by health professionals involved in the care of patients with IBD. The experts generated a set of recommendations. RESULTS: There are multiple DHT for IBD with different characteristics and contents. We received 29 questionnaires. Almost 50% of the participants were 41-50 years old, the majority were women (83%) and 90% were gastroenterologists. A total of 96% reported the use of several DHT, but 20% used them occasionally or infrequently. Web pages were found the most used (62%). DHT are mostly used to get information (80%), followed by clinical practice issues (70%) and educational purposes (62%). G-Educainflamatoria website is the best known and most used HDS (96% and 64%, respectively). The main barriers to the use of DHT in IBD were the lack of time (55%), doubts about the benefit of DHT (50%) and the excess of information (40%). CONCLUSIONS: Healthcare professionals involved in the care of patients with to IBD frequently use DHT, although actions are needed to optimize their use and to guarantee their efficient and safe use.

Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Effectiveness and safety of adalimumab biosimilar in patients with inflammatory bowel disease.

BACKGROUND: Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce. METHODS: Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, 5 were directly started on MSB11022, and 9 switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index (HBI) have been usEd.) for Crohn's disease and Mayo Score for Ulcerative Colitis. Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab. RESULTS: No significant differences were observed in clinical disease activity (P=.317) or biochemical parameters [fecal calprotectin (P=.445) and C-reactive protein P=.661)] after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (P=.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects. CONCLUSIONS: Between originator adalimumab and biosimilar-start cohorts, no differences were observed, between originator adalimumab and switch cohorts, no significant differences were found either, and with the pre- and post-switch to biosimilar comparison, 2 of the 9 patients experienced AEs after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect (rash) with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

OBJECTIVE: In this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. METHODS: The study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. RESULTS: Of the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04-67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. CONCLUSION: Our study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.

Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis. / Monitorización terapéutica de los fármacos biológicos en la enfermedad inflamatoria intestinal. Documento de Posicionamiento del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU).

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). METHODS: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. RESULTS: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations. CONCLUSIONS: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Incidence of herpes zoster in patients with inflammatory bowel disease. / Incidencia de herpes zóster en pacientes con enfermedad inflamatoria intestinal: estudio observacional y retrospectivo en dos hospitales españoles de tercer nivel.

BACKGROUND: Herpes zoster (HZ) is a prevalent disease caused by the reactivation of the varicella-zoster virus (VZV) and associated with chronic morbidity, particularly with post-herpetic neuralgia (PHN). Inflammatory bowel disease (IBD) has been associated with an increased risk of HZ, mainly when immunosuppressive treatment (IMT) is used. However, studies assessing the risk of HZ in IBD are scarce. AIMS: To evaluate the incidence rate and risk factors of HZ in IBD. METHODS: Retrospective study in IBD patients with a positive VVZ serology from two referral hospitals from the area of Barcelona. Diagnosis of HZ and its clinical features were recorded. RESULTS: A total of 398 IBD patients with a positive IgG-VVZ serology were identified. Fifty-eight percent of the patients received IMT (46.5% immunosuppressants monotherapy, 20.6% biologics monotherapy and, 32.7% combination therapy). After a median follow-up of 71 months (IQR 41.5-138.0), 17 (4.3%) patients developed HZ (cumulative incidence of 5.2 per 1000 person-year), 12 of them (70.6%) while receiving IMT. Median age at HZ episode was 38 years (IQR 27.5-52.5). Two (11%) developed PHN. Biological therapy was the only risk factor for developing HZ (OR 3.8 IC 95% 1.3-11.5; p=0.018). CONCLUSIONS: HZ is quite prevalent in IBD, occurring at early ages and particularly among patients using IMT. NPH appears to occur in a notable proportion of cases.

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease-EXVEDOCOL.

BACKGROUND: Real-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. METHODS: EXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. RESULTS: Thirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. CONCLUSIONS: High clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). / Impacto de la mesalazina en la respuesta a la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal. Resultados de un estudio prospectivo multicéntrico de GETECCU (VACOVEII).

OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.

Selective granulocyte-monocyte apheresis during induction with vedolizumab in moderate-severe ulcerative colitis: Experience in a tertiary hospital.

AIM: Granulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate-severe UC and incomplete response to steroids. PATIENTS AND METHODS: Single-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded. RESULTS: The study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4-5; 3-10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39-74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378µg/g (IQR: 924-5778µg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3-113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed. CONCLUSIONS: GMA+VDZ during induction can be effective and safe in selected patients with moderate-severe UC and partial response to steroids.

Combination of granulocyte-monocyte apheresis and tofacitinib: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. PATIENTS AND METHODS: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. CONCLUSION: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.