Non-fistulising perianal lesions (NFPL) in Crohn’s disease—including skin tags, fissures, ulcers, and anorectal strictures—are poorly described. Moreover, evidence on treatment response is scarce and heterogeneous, limiting therapeutic decision-making. We aimed to characterise NFPL in a real-world nationwide cohort and to evaluate therapeutic strategies and clinical outcomes. Adult CD patients with NFPL (fissures, ulcers, strictures) recorded in the prospectively maintained ENEIDA registry of GETECCU, were included. Demographics, and clinical characteristics were collected. Clinical records were additionally reviewed to obtain detailed information on NFPL features and treatments received. The frequency of NFPL within the registry population was calculated. For treatment evaluation (fissures), only patients with ≥12-week follow-up after NFPL diagnosis were analysed. Clinical response was defined as complete healing of the lesion according to physician assessment. Treatment strategies for NFPL were evaluated across therapeutic lines (first, second and third). Global therapeutic response was defined as complete healing at any therapeutic line of the same treatment. Among 36,661 patients with Crohn’s disease included in ENEIDA, 8,667 had perianal disease. Of these, 2,434 patients (28%, 95% CI = 28-29%) had NFPL. We included 490 patients (mean age at NFPL diagnosis: 34 years; male: 51%; Montreal location L1/L2/L3: 36%/24%/40%; behaviour B1/B2/B3: 70%/13%/17%; concomitant fistulising perianal disease: 33%). Anal fissure was the most frequent lesion (417/490; 85%), followed by anorectal strictures (53/490; 11%) and cavitating ulcers (52/490; 11%). Clinical characteristics of these patients are detailed in table 1. For treatment analysis, 417 patients with fissures and complete follow-up were evaluated (female: 51%; location L1/L2/L3: 39%/22%/39%; behaviour B1/B2/B3: 72%/16%/16%; concomitant fistulising perianal disease: 31%). First-line therapy induced clinical healing in 66% (224/341; 95% CI 60–71%): vasodilators 63%, botulinum toxin 60%, surgery 95%, biologics 54%. Global therapeutic response was: vasodilators 80%, surgery 78%, botulinum toxin 76%, biologics 77%. Overall, 70% (291/417) of patients achieved clinical healing of the fissure. Non-fistulising perianal lesions are common in Crohn’s disease and respond favourably to standard therapies. In a real-world nationwide cohort, anal fissures predominated, and two-thirds of patients responded to first-line therapy, with overall 70% of patients achieving complete healing, supporting that these lesions should be recognised, diagnosed early, and treated following structured therapeutic pathways. Reference: *M. Chaparro and JP. Gisbert share senior authorship. Conflict of interest: Dr. Casanova, María José: María José Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie, and research funding from Lilly. De Francisco Garcia, Ruth Maria: No conflict of interest López Ramos, Carmen: No conflict of interest Hernandez Camba, Alejandro: I have served as a speaker or has received research or education funding or advisory fees from Lilly, Takeda, J and J, FAES Pharma, Falk, Abbvie, Adacyte Therapeutics, Tyllots, Ferring, Kern Pharma, Alfasigma and Chiesi. Gargayo-Puyuelo, Carla: No conflict of interest Castro Senosiain, Beatriz: No conflict of interest Mesonero Gismero, Francisco: I ve served as a speaker for and received consulting fees from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring Pharmaceuticals, Kern Pharma, Dr. Falk Pharma, Galapagos, Lilly, Chiesi Farmaceutici, and Faes Farma. Pagola, Leire: No conflict of interest Artero Cruañas, Arnau: No conflicts. Giordano, Antonio: Antonio Giordano received educational funds from Johnson & Johnson, Abbvie, Alfasigma, Ferring, Kern Pharma, and Dr. Falk. Ponferrada Diaz, Angel: financial support for travelling and educational activities from Johnsson and Johnsson, AbbVie, Takeda, Alfasigma, Lilly, Faes Farma and Ferring. Madero Velázquez, Lucía: None Robledo-Andrés, Pilar: Pilar Robledo have participated in scientific meetings, conferences, and consultancy activities for Lilly, Janssen, AbbVie, Takeda, Pfizer, MSD, Faes, Dr Falk, Galápagos, and Tillotts Pharma. Regueiro, Cristina: No conflict of interest Sampedro Gonzalez, Manuela: No conflict of interest Alvarado Jara, Rubén: No conflict of interest Ceballos Santos, Daniel: No conflict of interest Betoré Glaría, Elena: No conflict of interest Marquès-Camí, Miquel: No conflicts Varela Trastoy, Pilar: No conflict of interest Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock. Robles de la Osa, Daniel: No conflict of interest Salmoral Luque, Rosario: Have received education support from Alfasigma, Janssen Teller, Marta: Marta Teller have received support for travelling ans educational activities from Abbvie, Alfasigma, faesfarma, falk, fferring, Johnson&Johson, Lilly, Takeda, Tillots, and has served as a speaker for Alfasigma, Norgine, Schwabe. Rubín De Célix, Cristina: Cristina Rubín de Célix has received education funding from Ferring, Tillotts Pharma, AbbVie, Sandoz, Alfasigma, Lilly, Norgine, MSD, Pfizer, Takeda, and Janssen Almela, Pedro: Tillotts Pharma, AbbVie, Sandoz, Alfasigma, Lilly, Norgine, MSD, Pfizer, Font-Ordeig, Guillem: Takeda, and Janssen. CR has served has a speaker for Takeda. Bujanda, Luis: No conflict of interest Orenga-Sánchez, Carmen: No conflict of interest Oliveras-Font, Berta: No conflict of interest Gilabert Alvarez, Pau: No conflict of interest Mena Sánchez, Raquel: No conflict of interest Delgado Guillena, Pedro Genaro: No conflict of interest Maroto Arce, Nuria: No conflict of interest Perez Martinez, Isabel: “No conflicts” Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson Roig Ramos, Cristina: CR has received support for conference attendance and education funding from Kern Pharma, Ferring, Alfasigma, Faes Farma, Pfizer and Takeda. Domènech Moral, Eugeni: Personal Fees: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. Other: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Alfasigma/Galapagos Biogen, Celltrion, Ferring, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Takeda, Tillots. Chaparro, María: Grants: Pfizer, Janssen, Biogen, Abbvie, Lilly Personal Fees: Pfizer, Faes, Lilly, Abbvie, Janssen Gisbert, Javier: Grant: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Personal Fees: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Other: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma.
Mirikizumab (MIRI) has shown efficacy over placebo in ulcerative colitis (UC) based on the data from the pivotal clinical trials. However, these results still need to be confirmed in clinical practice. This study aims to assess the short-term real-world effectiveness and safety of MIRI in patients with UC. All patients with UC who received MIRI and without previous colectomy included in the prospectively-maintained ENEIDA registry were included. Clinical disease activity was assessed by partial Mayo score (pMS). The primary outcome was clinical remission (defined as pMS ≤2 with no subscore >1 and no rectal bleeding) at week 8 and 12, alongside its safety profile. A total of 269 patients from 44 Spanish hospitals were included (mean age of 50.6 years [SD 17], 54% male, median disease duration of 125 months [SD 94], 55% non-smokers, 58% extensive colitis. Concomitant therapy at baseline included 42% with steroids and 9% with immunosuppressants. Prior advanced therapies exposure was: 85% Anti-TNF, 62% vedolizumab, 46% ustekinumab, and 36% JAK inhibitors, with 77% exposed to 2 or more than 2 mechanisms of action (MoA).At baseline patients had a median pMS 5 (IQR, 4-6) and faecal calprotectin of 1011 ug/g (IQR, 412-2463). All but one patient started MIRI 300 mg iv every 4 weeks. Mean follow-up was 8.4 (SD 10.4) months. Clinical response and clinical remission at week 8 were 46% and 32%, respectively, and 44% and 37% at week 12.Clinical remission rate at week 12 was higher among those with prior exposure to 1 MoA vs 2 or more than 2 (61.5%, 36.8%, 26.4% respectively, p = 0.001, p = 0.001, figure 1).Previous exposure to ustekinumab was associated with a significant lower rate of clinical remission at week 12 (29.6% vs. 44.2%, p = 0.028). Faecal calprotectin and pMS significantly decreased at week 12 (400 ug/g [IQR, 127-1280], p = 0.001 and 2 [IQR, 0-4], p = 0.038).The overall cumulative hospitalization and colectomy rates were 5.2% and 2.6% respectively. MIRI was generally well tolerated, with 26 (10%) of patients reporting at least one adverse event, but only 3 of them categorized as severe. MIRI demonstrated its real-life effectiveness in the short-term, even in a highly-refractory cohort. Prior advanced therapy exposure to more than one MoA significantly impacts the effectiveness of MIRI during the induction. Safety was consistent with the known profile of this drug. Conflict of interest: Prof. Gutiérrez Casbas, Ana: Consultant for: AbbVie, Amgen, Celltrion, Lilly, Ferring, Galapagos, Fresenius Kabi, J & J, Pfizer, Sandoz, Takeda. Speaker’s Fees for: AbbVie, Amgen, Bristol-Myers Squibb, Lilly, Ferring, Fresenius Kabi, Glaxo-Smith Kline, J & J, Pfizer, Roche, Sandoz, Shire, Takeda. Advisory Boards for: AbbVie, Amgen, Biogen, Lilly, Ferring, Fresenius Kabi, Glaxo-Smith Kline, Janssen, Merck, Pfizer, Sandoz, Takeda. Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock. De Castro Parga, Maria Luisa: No conflict of interest Madero Velázquez, Lucía: No conflict of interest Rodríguez, Cristina: No conflict of interest Aguas, Peris: Mariam Aguas has served as a speaker or has received research or education funding or advisory fees from AbbVie, Abbott, Alfasigma, Faes, Dr. Falk, Ferring, Kern Pharma, Janssen, Lilly, Norgine and STADA. Huguet, José María: Jose M. Huguet has served as a speaker and consultant for or has received research funding from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Sandoz, Tillotts Pharma, Dr. Falk Pharma and Faes Farma. Diz Lois Palomares, Maria Teresa: No conflict of interest Bermejo San Jose, Fernando: No conflict of interest Fernandez Clotet, Agnes: No conflict of interest Ber, Yolanda: No conflict of interest Antón, María Rosario: No conflict of interest Olivares, Sonsoles: No conflict of interest Sierra Ausín, Mónica: Mónica Sierra-Ausín has served as speaker or has received research or education funding or advisory fees from AbbVie, Ferring, Janssen, Lilly, Pfizer, Takeda and Pfizer. Robles-Osa, Daniel: No conflict of interest Moralejo Lozano, Óscar: No conflict of interest Martin Arranz, Maria Dolores: María Dolores Martín-Arranz has served as a speaker or has received research or education funding or advisory fees from AbbVie, Pfizer, Takeda, Janssen, TillottsPharma, Lilly and Galapagos. Cotaina, Andrea: No conflict of interest Fueyo, Pablo: IM-J has served as a speaker, a consultant and advisory member for or has received research funding from AbbVie, Amgen, Chiesi, Dr. Falk Pharma, Faes Farma, Ferring, Fresenius, Galapagos, Gebro Pharma, Janssen, Kern Pharma, Lilly, MSD, Otsuka Pharmaceutical, Pfizer, Sandoz, Shire Pharmaceuticals, Takeda, Tillotts Pharma and Vifor Pharma. Ramirez Palanca, Jose Joaquin: No conflict of interest García-Bosch, Orlando: No conflict of interest Trapero Martinez, Ana María: No conflict of interest Brunet, Eduard: No conflict of interest Varela Trastoy, Pilar: No conflict of interest De Francisco Garcia, Ruth Maria: RDF has received support for congress and conference attendance and education funding from Pfizer, AbbVie, Tillots, Takeda, Ferring and Janssen. Ceballos Santos, Daniel: DC has served as speaker, consultant and advisory board or has received research funding from MSD, AbbVie, Janssen, Takeda, Biogen, Lilly, Sandoz, Ferring, Adacyte, Faes Farma, Kern Pharma, Pfizer, Vifor Pharma, Chiesi, and Tillotts. Ponferrada Diaz, Angel: AP has served as a speaker or has received research or education funding or advisory fees from Lilly, Takeda, J and J, FAES Pharma, Falk, AbbVie, Kern Pharma and Alfasigma. Gómez Espín, Rosa María: No conflict of interest Rodriguez Moranta, Francisco: FR-M has served as a speaker and has received research or education funding or advisory fees from Lilly, Takeda, J&J, FAES Pharma, Falk, AbbVie, Pfizer, Tyllots, Ferring and Kern Pharma. Zabana, Yamile: YZ has received support for conference attendance, speaker fees, research support and consulting fees from: AbbVie, Adacyte Therapeutics, Alfa-Sigma, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, J and J, Kern Pharma, Lilly, MSD, Pfizer, Sanofi, Sandoz, Takeda and Tillots Pharma. Elorza, Ainara: No conflict of interest Manceñido Marcos, Noemí: NMM has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie,Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and TillotsPharma Sampedro Gonzalez, Manuela: No conflict of interest Betoré Glaría, Elena: No conflict of interest Calvo, María: No conflict of interest Ferrer, Juan: No conflict of interest Marcos Carrasco, Natalia: No conflict of interest Mena Sánchez, Raquel: No conflict of interest Domènech Moral, Eugeni: ED has served as a speaker or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Ferring, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Samsung, Takeda and Tillots. Rodríguez-Lago, Iago: No conflict of interest
Comparative studies using induced pluripotent stem cells (iPSCs) from patients with those from healthy individuals as controls are flawed by genetic background contribution to disease phenotype. Here, we used precise gene editing to generate gene-corrected isogenic control lines for a single pathogenic variant in the USH2A gene (c.2276G > T) associated with retinitis pigmentosa (RP). Both homozygously and heterozygously corrected cell lines were successfully generated. These cell lines will serve to unravel RP phenotype differences specific to the USH2A mutation upon their conversion into disease relevant cell types.
Background and aims: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. Method: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. Results: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p < 0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p < 0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after PegINF). An additional 10% of patients developed cirrhosis (n = 137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. Conclusion: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present. (c) 2024 Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
BACKGROUND AND AIMS:Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Colonoscopy is the diagnostic gold standard, although its performance in symptomatic patients is limited. During the COVID-19 pandemic, the AEG-SEED societies proposed a clinical prioritization system. The aim of this study was to validate its diagnostic performance in detecting clinically relevant lesions (CRLs), including CRC, and to compare it with the fecal immunochemical test (FIT). PATIENTS AND METHODS:A national multicenter retrospective study was conducted in 12 Spanish hospitals. A total of 1078 adult patients with digestive symptoms attended between April and December 2020 were included. Colonoscopies were prospectively classified according to priority levels (P1, P2, P3). RESULTS:CRLs were identified in 18% of patients, including 36 cases of CRC (3%). The diagnostic yield was highest in P1 (PPV 27%, AUC 0.57 for CRLs; PPV 7%, AUC 0.64 for CRC), and decreased in P2 and P3. FIT was performed in 26% of patients based on the referring physician's clinical judgment, showing higher sensitivity and negative predictive value (NPV) for CRC (100%) and a higher AUC (0.69) compared to clinical criteria. CONCLUSIONS:The AEG-SEED clinical criteria offer moderate value for prioritizing colonoscopies in the absence of FIT. However, FIT demonstrates superior diagnostic performance and should be systematically incorporated. The combination of symptoms improves accuracy compared to isolated symptoms.
