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Background: The success of anti-tumor necrosis factor (TNF) drug strategies in the treatment of inflammatory bowel disease (IBD) is altered by the development of anti-drug antibodies that reduce their efficacy. Studies have shown that the HLA-DQA1⋆05 allele increases the risk of immunogenicity to anti-TNF drugs approximately twofold. Objective: Analyze whether the presence of the HLA-DQA1⋆05 allele is associated with the development of immunogenicity and to evaluate the disease response to anti-TNF drugs (infliximab (IFX) and adalimumab (ADA)), according to the presence of this allele. Design: This is an observational retrospective cohort study, single center, to determine the impact of HLA-DQA1⋆05 on disease activity in patients with IBD at the Hospital Universitario Virgen Macarena. Methods: In total, 200 IBD patients were included: 109 treated with IFX and 91 with ADA. Data were collected using the computerized medical records from the DIRAYA program of the Servicio Andaluz de Salud. Response—defined as improvement—and remission—defined as the disappearance of symptoms and analytical/endoscopic signs—were assessed using activity indices (partial Mayo, Harvey–Bradshaw) in all patients. Anti-TNF drug levels were also determined, as well as the presence or absence of anti-IFX and anti-ADA antibodies. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results: The HLA-DQA1⋆05 haplotype was present in 70 (35%) patients, including 39 (36%) treated with IFX and 31 (34%) with ADA. The risk of withdrawal, intensification, as well as antibody development, was higher in patients carrying the allele and on treatment with IFX or ADA. Conclusion: In our study, we demonstrated that there is an increased risk of immunogenicity in patients carrying the HLA-DQA1⋆05 genotype, which would support the idea of screening for this genetic variant before starting anti-TNF therapy, as its prevalence is high in the general population and increases the risk of treatment discontinuation due to loss of response.

Background: Ustekinumab (UST) is an effective treatment option in Crohn’s disease (CD) and ulcerative colitis (UC). However, it still remains unclear if therapeutic drug monitoring could be helpful to guide clinicians. Objectives: The aim of our study was to analyze the relationship between UST through levels (UST TL ) and clinical outcomes in real-world inflammatory bowel disease (IBD) patients. Design: We performed a unicentric retrospective study including patients with IBD under UST treatment with at least one level determination. Methods: The following variables were analyzed at the initiation of UST and at each UST TL measurement: clinical response and remission using the Harvey–Bradshaw Index (HBI) for CD and the Partial Mayo Score (pMayo) for UC; biochemical response and remission using fecal calprotectin and C-reactive protein, among others. Two periods were considered: P1 (time between induction and the first determination of UST TL ) and P2 (time between UST TL1 and the second determination of UST TL ). Results: We included 125 patients, 117 with CD. In P1, 62.4% of patients were on subcutaneous maintenance, and the median UST TL1 was 3.1 μg/mL (1.6–5.3). In 44.8% of CD patients (48/117), clinical remission was achieved, with UST TL1 significantly higher than those who did not achieve remission (3.7 μg/mL (2.3–5.4) vs 2.3 μg/mL (1.1–5.2); p = 0.04). In the 46 patients with two determinations, statistically significant differences were found between variables in P2 versus P1: clinical remission (73.9% vs 21.7%; p = 0.001); UST TL (7.2 μg/mL (4.7–11.7) vs 3.4 μg/mL (1.9–6.4); p

IntroductionCrohn’s disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1β pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue.MethodsMaqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1β levels.ResultsCompared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1β levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed.ConclusionThese outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).

Background: Ustekinumab (UST) is indicated for the treatment of Crohn’s disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. Objectives: The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST. Design: We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST. Methods: The clinical response and remission was analyzed at week 12, defined as either Harvey–Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed. Results: We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study. Conclusions: IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.

Background: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD) and can result in reduced quality of life and increased healthcare costs. IDA is treated with iron supplementation, commonly with intravenous iron formulations, such as ferric carboxymaltose (FCM), and iron sucrose (IS). Methods: This study assessed the cost-effectiveness of FCM compared with IS, in terms of additional cost per additional responder in patients with IDA subsequent to IBD in the Spanish setting. An economic model was developed to assess the additional cost per additional responder, defined as normalization or an increase of ⩾2 g/dl in hemoglobin levels, for FCM versus IS from a Spanish healthcare payer perspective. Efficacy inputs were taken from a randomized controlled trial comparing the two interventions (FERGIcor). Costs of treatment were calculated in 2021 Euros (EUR) using a microcosting approach and included the costs of intravenous iron, healthcare professional time, and consumables. Cost-effectiveness was assessed over one cycle of treatment, with a series of sensitivity analyses performed to test the robustness of the results. Results: FCM was more effective than IS, with 84% of patients achieving a response compared with 76%. When expressed as number needed to treat, 13 patients would need to switch treatment from IS to FCM in order to achieve one additional responder. Costs of treatment were EUR 323 with FCM compared with EUR 470 with IS, a cost saving of EUR 147 with FCM. Cost savings with FCM were driven by the reduced number of infusions required, resulting in a reduced requirement for healthcare professional time and use of consumables compared with the IS arm. Conclusion: The present analysis suggests that FCM is less costly and more effective than IS for the treatment of IDA subsequent to IBD in Spain and therefore was considered dominant.

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain.MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients.ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses.ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Background and study aims: Endoscopy plays an essential role in managing patients with ulcerative colitis (UC), as it allows us to visualize and assess the severity of the disease. As such assessments are not always objective, different scores have been devised to standardize the findings. The main aim of this study was to assess the interobserver variability between the Mayo Endoscopy Score (MES), Ulcerative Colitis Endoscopy Index of Severity (UCEIS) and Ulcerative Colitis Colonoscopy Index of Severity (UCCIS) analyzing the severity of the endoscopic lesions in patients with ulcerative colitis. Patients and methods: This was a single-cohort observational study in which a colonoscopy was carried out on patients with UC, as normal clinical practice, and a video was recorded. The results from the video were classified according to the MES, UCEIS and UCCIS by three endoscopic specialists independently, and they were compared to each other. The Mayo Endoscopy Score (MES) was used to assess the clinical situation of the patient. The therapeutic impact was analyzed after colonoscopy was carried out. Results: Sixty-seven patients were included in the study. The average age was 51 (SD ± 16.7) and the average MES was 3.07 (SD ± 2.54). The weighted Kappa index between endoscopists A and B for the MES was 0.8; between A and C 0.52; and between B and C 0.49. The intraclass correlation coefficient for UCEIS was 0.92 among the three endoscopists (CI 95 %: 0.83–0.96) and 0.96 for UCCIS among the three endoscopists (CI 95 % 0.94–0.97). A change in treatment for 34.3 % of the patients was implemented on seeing the results of the colonoscopy. Conclusions: There was an adequate, but not perfect, correlation between the different endoscopists for MES, UCEIS, UCCIS. This was higher with the last two scores. Thus, there is still some subjectivity to be minimized through special training, on assessing the seriousness of the endoscopic lesions in patients with UC.

Objective To evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFα) therapy.Design Data from 310 patients (194 with Crohn’s disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFα in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFα treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model.Results Multivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFα, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease).Conclusions Our results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFα treatment. Therefore, their presence should be considered when choosing a treatment.Trial registration number NCT02861118.

ABSTRACT Background and aims: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. Methods: this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade(r)) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. Results: a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. Conclusion: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.

Background: Several studies have reported positive efficacy outcomes for patients with inflammatory bowel disease treated with CT-P13, an infliximab biosimilar. Data from follow-up periods longer than 1 year are still scarce. Here, we assessed the long-term efficacy data, loss of response and safety after switching from infliximab to CT-P13 in patients with inflammatory bowel disease. Methods: This was a prospective single-center observational study involving patients with moderate-to-severe Crohn’s disease and ulcerative colitis switched from infliximab to CT-P13 treatment and reviewed up to 24 months. Efficacy and loss of response were measured using the Harvey–Bradshaw (HB) index and partial Mayo score for patients with Crohn’s disease and ulcerative colitis respectively. C-reactive protein, infliximab drug levels, adverse events and antidrug antibodies were also monitored throughout the study. Results: A total of 64 patients with Crohn’s disease and 36 patients with ulcerative colitis were included. Most of them (72%) remained on CT-P13. Overall, 28% of patients discontinued the therapy due to loss of response, adverse events or long-lasting clinical remission. Remission at 18 and 24 months occurred in 69.9% and 68.5% of patients, respectively. Dose increase was performed in 22% of patients, with remission being reached in 60% of them. HB index, partial Mayo score, C-reactive protein and infliximab drug levels did not show significant changes. Serious adverse events were reported in 14% of patients. Overall, two patients developed low levels of antidrug antibodies. Conclusions: Most of the patients switching from original infliximab were maintained on CT-P13 at 2 years of follow up with a good profile of efficacy and safety.

The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin–Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui’s anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).

Introduction: In the last few years a significant number of papers have related the use of proton-pump inhibitors (PPIs) to potential serious adverse effects that have resulted in social unrest. Objective: The goal of this paper was to provide a literature review for the development of an institutional position statement by Sociedad Española de Patología Digestiva (SEPD) regarding the safety of long-term PPI use. Material and methods: A comprehensive review of the literature was performed to draw conclusions based on a critical assessment of the following: a) current PPI indications; b) vitamin B12 deficiency and neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric infection and pneumonia; f) interactions with thienopyridine derivatives; e) complications in cirrhotic patients. Results: Current PPI indications have remained unchanged for years now, and are well established. A general screening of vitamin B12 levels is not recommended for all patients on a PPI; however, it does seem necessary that magnesium levels be measured at therapy onset, and then monitored in subjects on other drugs that may induce hypomagnesemia. A higher risk for bone fractures is present, even though causality cannot be concluded for this association. The association between PPIs and infection with Clostridium difficile is mild to moderate, and the risk for pneumonia is low. In patients with cardiovascular risk receiving thienopyridines derivatives it is prudent to adequately consider gastrointestinal and cardiovascular risks, given the absence of definitive evidence regardin potential drug-drug interactions; if gastrointestinal risk is found to be moderate or high, effective prevention should be in place with a PPI. PPIs should be cautiously indicated in patients with decompensated cirrhosis. Conclusions: PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and duration are appropriate.

The complexity of some diseases—as well as the inherent toxicity of certain drugs—has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients—or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included.

Introduction: Capsule endoscopy (CE) in children has limitations based mainly on age. The objective of this consensus was reviewing the scientific evidence. Material and methods: Some experts from the Spanish Society of Gastroenterology (SEPD) and Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP) were invited to answer different issues about CE in children. These sections were: a) Indications, contraindications and limitations; b) efficacy of CE in different clinical scenarios; c) CE performance; d) CE-related complications; e) Patency capsule; and f) colon capsule endoscopy. They reviewed relevant questions on each topic. Results: The main indication is Crohn's disease (CD). There is no contraindication for the age and in the event that the patient not to swallow it, it should be administered under deep sedation with endoscopy and specific device. The CE is useful in CD, for the management of OGIB in children and in Peutz-Jeghers syndrome (in this indication has the most effectiveness). The main complication is retention, which should be specially taken into account in cases of CD already diagnosed with malnutrition. A preparation regimen based on a low volume of polyethylene glycol (PEG) the day before plus simethicone on the same day is the best one in terms of cleanliness although does not improve the results of the CE procedure. Conclusions: CE is safe and useful in children. Indications are similar to those of adults, the main one is CD to establish both a diagnosis and disease extension. Moreover, only few limitations are detected in children.

Introduction and aims: The understanding of lactose intolerance (LI) is limited in some professional settings. Sociedad Española de Patología Digestiva (SEPD) and Sociedad Española de Medicina General (SEMG) have developed a survey in order to: a) Analyze primary care physicians (PCPs) knowledge and clinical management; and b) to compare results with those of a previous survey of Spanish gastroenterologists (GEs). Material and methods: An online questionnaire was sent to SEMG members with 27 items on various issues: Demographics, occupational characteristics, outlook on LI, diagnostic tests, treatment, and follow-up. Results were compared to those from a survey of GEs. Results: A total of 456 PCPs responded, versus 477 GEs. PCPs had an older mean age and longer professional experience. Level of understanding of LI was similar, albeit a higher proportion of PCPs lacked epidemiological awareness (p < 0.01). GEs tended to consider LI a "minor" condition (71.3 vs. 40.1%; p > 0.001), and LI symptoms as overlapping those of irritable bowel syndrome (93.5 vs. 88.2%; p = 0.005), although symptoms perceived as suspicious of LI were similar in both groups. Dietary recommendations were recognized as the primary therapeutic approach. Conclusion: This study reveals the outlook of PCPs on LI, and allows comparison with that of GEs, as a basis for the development of strategies aimed at improving LI understanding, approach and management in our setting.

Introduction: PillCam© colon capsule endoscopy (CCE) enables the study of colonic diseases in a safe and non-invasive way, although there are aspects that need to be improved. Current methods of bowel preparation lead to discordant rates of adequate cleansing and CCE excretion. Aims: To compare the efficacy of colon cleansing using two different regimes (2L PEG plus ascorbic acid versus 4L PEG alone) for PillCam Colon (C2) capsule endoscopy. Methods: Fifty eight patients included in this prospective study and randomized to: Group A, PEG plus ascorbic acid regimen (n = 28, 12 F/16 M) or group B, PEG alone regimen (n = 30, 14 F/16 M). The degree of cleansing was categorized into "excellent-good" or "fair-poor", according to Leighton's recently published preparation scale. CCE excretion rate and colon cleansing were assessed. Patients underwent to PillCam colon of second generation (C2). Results: Cleansing was considered to be excellent-good in 78 % of cases in group A and in 64 % of cases in group B, with no significant difference between the groups (p = 0.252). Nevertheless, when the grade of cleansing was analyzed in segments, a significant difference was found in the cecum and transverse colon. No differences were observed in the bubble effect between preparations. The excretion rate was 93 % in group A versus 70 % in group B (p = 0.043). Conclusions: These results suggest that a 2L PEG plus ascorbic acid regimen is at least as effective as a 4L PEG regimen. This regimen may be considered an effective alternative which would improve compliance because a smaller volume is required.

Biological drugs or biopharmaceutical products, manufactured with or from living organisms using biotechnology, have represented a therapeutic revolution for the control of inflammatory bowel disease (IBD). At present, in this indication and in our country, only two biologicals are approved, infliximab (IFX) and adalimumab (ADA), both of them monoclonal antibodies against tumor necrosis factor alpha. Effectiveness data are strong for both therapies, with maximum levels of scientific evidence. The upcoming expiry date for these biologicals' patents has allowed the potential marketing of so-called biosimilar agents for the IBD indication. While biosimilars are conceptually for biologicals what generics are for chemical drugs, the structural complexity of biosimilars and their biological and manufacturing variability lead to consider validation processes for these two types in humans as highly differential. Thus, in our setting, under the coverage of "Agencia Española del Medicamento y Productos Sanitarios (AEMPS)" (Spanish Agency of Medicines and Medical Devices), guidelines issued by the European Medicines Agency (EMA) are to be applied, which states that a number of stages or steps must be overcome in order to obtain approval for a biosimilar agent. However, despite the presence of these recommendations by EMA, which must be met by a biosimilar in order to be licensed in our marketplace, relevant uncertainties persist that only future decisions by EMA and AEMPS may clarify. The present stance by our task force is that biosimilar development should be undertaken according to established regulations, thus certifying their efficacy and safety. Similarly, this task force considers that results obtained from studies in rheumatoid arthritis (RA) should not be extrapolated to IBD since the biological variability of these complex structures will not ensure a lack of noticeable changes in efficacy and safety.Los productos biofarmacéuticos, o medicamentos biológicos, fabricados mediante, o a partir de organismos vivos utilizando biotecnología, han supuesto una revolución terapéutica en el control de la enfermedad inflamatoria intestinal (EII). Al presente, en esta indicación y en nuestro país, solo se dispone de dos biológicos autorizados, infliximab (IFX) y adalimumab (ADA), ambos anticuerpos monoclonales frente al factor de necrosis tumoral alfa. La evidencia de eficacia con ambos tratamientos es sólida con niveles de evidencia científica máxima. La proximidad de la expiración de las patentes de estos dos biológicos ha abierto la posibilidad de entrada en el mercado de los denominados biosimilares en la indicación de tratamiento de la EII. Aunque conceptualmente los biosimilares son para los medicamentos biológicos lo que los genéricos para los químicos, la complejidad estructural de los biosimilares, así como su propia variabilidad biológica y la de su producción, obligan a considerar como muy diferentes los procesos de validación de su uso en humanos respecto de los mencionados genéricos. Así, en nuestro medio, y contando con la garantía de la Agencia Española del Medicamento y Productos Sanitarios (AEMPS), son de aplicación las reglas del juego dictadas por la "European Medicines Agency" (EMA) que ha establecido una serie de etapas o escalones a superar antes de poder obtener la aprobación para un biosimilar. No obstante, a pesar de la existencia de estas recomendaciones de la EMA, que deben cumplirse para que un biosimilar sea aprobado en nuestro mercado, persisten algunas incertidumbres relevantes que solo las futuras decisiones de la EMA y de la AEMPS pueden aclarar. La posición del presente grupo de trabajo es que el desarrollo de un biosimilar debe hacerse en el contexto de las normas establecidas certificando de esta manera su eficacia y seguridad. Igualmente este grupo de trabajo considera que no deben extrapolarse los resultados obtenidos en los estudios realizados en artritis reumatoide (AR) a la EII, en base a que la variabilidad biológica de estas complejas estructuras no garantiza la ausencia de notables cambios en eficacia y seguridad.

Background: in most cases, inflammatory bowel disease (IBD) debuts at reproductive age. The data available in the literature show infliximab (IFX) to be a safe drug during pregnancy but there is very little evidence about the activity of the disease following drug withdrawal during pregnancy. Aims: determine the drug´s safety in pregnant women in our setting and assess its effect on the foetus, drawing on the experience of several hospitals. Secondly, observe the effect of treatment withdrawal on disease activity during pregnancy. Material and methods: a retrospective study was conducted of women with IBD who had received IFX treatment during pregnancy in five hospitals in Spain. Disease activity was assessed using Crohn´s Disease Activity Index, while UC was assessed using the Truelove-Witts Index in each trimester of pregnancy. Gestational age, weight and diseases in the foetus were determined at birth. Results: the study included 12 women with a mean age of 29 years; 4 had ulcerative colitis and 8 Crohn´s disease, with mean disease duration of 7 years. All but one, who was diagnosed during pregnancy, was receiving IFX treatment at conception. Six patients received uninterrupted treatment throughout the pregnancy, 2 requested voluntary interruption and in 3 cases treatment was interrupted in the third trimester as a precaution. They received a mean IFX dose of 400 mg every 8 weeks. Of the 6 patients who received continuous treatment, in 50% disease was held in remission. The 6 remaining patients suspended treatment for different reasons, presenting disease recurrence in all but one case (83.3%). Eight deliveries were vaginal and 4 by caesarean section. Newborns presented no congenital anomalies, intrauterine growth retardation or low birth weight and there was only one premature delivery. Conclusions: although cases included in the stduy are not significant, in our experience, IFX during pregnancy is a safe treatment for the mother and the foetus. In fact, in our study and in some cases, its withdrawal may lead to a worsening of the disease. However, further control studies are required with larger samples to obtain more representative findings.Introducción: la enfermedad inflamatoria intestinal (EII) es un trastorno crónico que debuta en la mayoría de los casos durante la edad reproductiva. Existen pocos datos sobre la seguridad durante el embarazo de los tratamientos disponibles, entre ellos los denominados biológicos, y estos están basados en resultados de casos esporádicos. Objetivos: determinar la seguridad del tratamiento con infliximab (IFX) durante el embarazo en mujeres con EII. Un segundo objetivo es observar el efecto que sobre la actividad de la enfermedad tiene el abandono del tratamiento. Material y métodos: se trata de un estudio retrospectivo en el que se incluyeron mujeres con EII embarazadas y que estaban en tratamiento con IFX durante el embarazo. Se incluyeron en el estudio a 5 hospitales de España. La actividad de la enfermedad se midió según el CDAI en la enfermedad de Crohn (EC) y la de la colitis ulcerosa (CU) según el índice de Truelove-Witts en cada trimestre del embarazo. La edad gestacional, el peso y las enfermedades del feto se determinaron al nacimiento. Resultados: se incluyeron doce mujeres con una edad media de 29 años, 4 diagnosticadas de CU y 8 de EC, con una duración media de la enfermedad de 7 años. Todas salvo una, que se diagnosticó durante el embarazo estaban siendo tratadas con IFX en el momento de la concepción. Seis pacientes recibieron el tratamiento de forma ininterrumpida durante todo el embarazo, 2 suspendieron el tratamiento de forma voluntaria y a tres se les suspendió el tratamiento en el tercer trimestre. Recibieron una dosis media de IFX de 400 mg cada 8 semanas. De las 6 pacientes que recibieron tratamiento continuo, el 50% se mantuvo en remisión. De las pacientes que abandonaron el tratamiento, un 83,3% (todas menos una) presentaron un brote de su enfermedad. Ocho partos fueron por vía vaginal y cuatro por cesárea. Ningún recién nacido presentó malformaciones congénitas, retraso del crecimiento intrauterino ni bajo peso y sólo hubo un parto prematuro. Conclusiones: aunque los casos incluidos en el estudio son pocos, según nuestra experiencia IFX es un fármaco seguro durante el embarazo para la madre y el feto. De hecho, parece que su suspensión puede conducir a un empeoramiento de la enfermedad. No obstante, son necesarios más estudios y con más pacientes para obtener resultados con mayor evidencia científica.

CD is a chronic inflammatory disorder associated to mucosal and transmural inflammation of the bowel wall. It is well known that CD can affect the entire gastrointestinal. Therefore, ileocolonoscopy and biopsies of the terminal ileum as well as of each colonic segment to look for microscopic evidence of CD are the first-line procedures to establish the diagnosis. However, it has been observed that up to 30% of the patients have only small bowel involvement. Evaluation of the small bowel has been made with radiological procedures, barium radiography, and abdominal computed tomography or by ileocolonoscopy or enteroscopy, but they have many recognized limitations. CE is undoubtedly a very useful diagnostic tool proposed to observe small-bowel lesions undetectable by conventional endoscopy or radiologic studies. We review different studies that have been published reporting the use of CE in suspected and evaluation of the extension or the recurrence in CD and also its use in pediatric population and its complications.