Use of biologics for the management of Crohn's disease: IG-IBD clinical guidelines based on the GRADE methodology

A cure for Crohn's disease (CD), a chronic inflammatory disease of the gastrointestinal tract of unknown etiology, is not available, so patients require lifelong management to keep inflammation under control. The therapeutic armamentarium has expanded with approval of several biological drugs, including in-fliximab, adalimumab, vedolizumab and ustekinumab - monoclonal antibodies that target different in-flammatory pathways - and darvadstrocel, a suspension of expanded human allogeneic, adipose-derived, mesenchymal stromal cells for the treatment of refractory complex perianal fistula. Notwithstanding ex-isting practice guidelines on medical therapy for CD, the Italian Group for the Study of Inflammatory Bowel Disease felt the need to issue new guidelines focused on the use of biologics for managing the intestinal manifestations of CD and based on the GRADE methodology. This document presents recom-mendations regarding six clinical settings, from the induction to the maintenance of clinical remission, and from optimization and de-escalation of treatments to dealing with perianal CD and post-operative recurrence. The 19 evidence-based statements are supported by information on the quality of the evi-dence, agreement rate among panel members, and panel comments mainly based on evidence from real world studies

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis

Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease: Data from ESCAPE-IBD, an IG-IBD study

Background Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) Methods Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Results 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%; p<0.001). HCs had higher antibody concentrations (median OD 8.72 [IQR 5.2-14-2]) compared to the whole cohort of IBD patients (median OD 1.54 [IQR 0.8-3.6]; p<0.001) and the subgroup of IBD patients (n=280) without any treatment or on aminosalicylates only (median OD 1.72 [IQR 1.0–4.1]; p<0.001). Conclusions Although most IBD patients showed seropositivity after COVID-19 vaccines, the magnitude of the humoral response was significantly lower than in HCs. Differently from other studies, these findings seem to be mostly unrelated to the use of immune-modifying treatments (ClinicalTrials.govID:NCT04769258)

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice

Intelligenza artificiale e sicurezza: opportunità, rischi e raccomandazioni

L'IA (o intelligenza artificiale) è una disciplina in forte espansione negli ultimi anni e lo sarà sempre più nel prossimo futuro: tuttavia è dal 1956 che l’IA studia l’emulazione dell’intelligenza da parte delle macchine, intese come software e in certi casi hardware. L’IA è nata dall’idea di costruire macchine che - ispirandosi ai processi legati all’intelligenza umana - siano in grado di risolvere problemi complessi, per i quali solitamente si ritiene che sia necessario un qualche tipo di ragionamento intelligente. La principale area di ricerca e applicazione attuale dell’IA è il machine learning (algoritmi che imparano e si adattano in base ai dati che ricevono), che negli ultimi anni ha trovato ampie applicazioni grazie alle reti neurali (modelli matematici composti da neuroni artificiali) che a loro volta hanno consentito la nascita del deep learning (reti neurali di maggiore complessità). Appartengono al mondo dell’IA anche i sistemi esperti, la visione artificiale, il riconoscimento vocale, l’elaborazione del linguaggio naturale, la robotica avanzata e alcune soluzioni di cybersecurity. Quando si parla di IA c'è chi ne è entusiasta pensando alle opportunità, altri sono preoccupati poiché temono tecnologie futuristiche di un mondo in cui i robot sostituiranno l'uomo, gli toglieranno il lavoro e decideranno al suo posto. In realtà l'IA è ampiamente utilizzata già oggi in molti campi, ad esempio nei cellulari, negli oggetti smart (IoT), nelle industry 4.0, per le smart city, nei sistemi di sicurezza informatica, nei sistemi di guida autonoma (drive o parking assistant), nei chat bot di vari siti web; questi sono solo alcuni esempi basati tutti su algoritmi tipici dell’intelligenza artificiale. Grazie all'IA le aziende possono avere svariati vantaggi nel fornire servizi avanzati, personalizzati, prevedere trend, anticipare le scelte degli utenti, ecc. Ma non è tutto oro quel che luccica: ci sono talvolta problemi tecnici, interrogativi etici, rischi di sicurezza, norme e legislazioni non del tutto chiare. Le organizzazioni che già adottano soluzioni basate sull’IA, o quelle che intendono farlo, potrebbero beneficiare di questa pubblicazione per approfondirne le opportunità, i rischi e le relative contromisure. La Community for Security del Clusit si augura che questa pubblicazione possa fornire ai lettori un utile quadro d’insieme di una realtà, come l’intelligenza artificiale, che ci accompagnerà sempre più nella vita personale, sociale e lavorativa.AI (or artificial intelligence) is a booming discipline in recent years and will be increasingly so in the near future.However, it is since 1956 that AI has been studying the emulation of intelligence by machines, understood as software and in some cases hardware. AI arose from the idea of building machines that-inspired by processes related to human intelligence-are able to solve complex problems, for which it is usually believed that some kind of intelligent reasoning is required. The main current area of AI research and application is machine learning (algorithms that learn and adapt based on the data they receive), which has found wide applications in recent years thanks to neural networks (mathematical models composed of artificial neurons), which in turn have enabled the emergence of deep learning (neural networks of greater complexity). Also belonging to the AI world are expert systems, computer vision, speech recognition, natural language processing, advanced robotics and some cybersecurity solutions. When it comes to AI there are those who are enthusiastic about it thinking of the opportunities, others are concerned as they fear futuristic technologies of a world where robots will replace humans, take away their jobs and make decisions for them. In reality, AI is already widely used in many fields, for example, in cell phones, smart objects (IoT), industries 4.0, for smart cities, cybersecurity systems, autonomous driving systems (drive or parking assistant), chat bots on various websites; these are just a few examples all based on typical artificial intelligence algorithms. Thanks to AI, companies can have a variety of advantages in providing advanced, personalized services, predicting trends, anticipating user choices, etc. But not all that glitters is gold: there are sometimes technical problems, ethical questions, security risks, and standards and legislation that are not entirely clear. Organizations already adopting AI-based solutions, or those planning to do so, could benefit from this publication to learn more about the opportunities, risks, and related countermeasures. Clusit's Community for Security hopes that this publication will provide readers with a useful overview of a reality, such as artificial intelligence, that will increasingly accompany us in our personal, social and working lives

A. Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease.

Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn’s disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failureof an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period

Gastrointestinal lesions associated with spondyloarthropathies

Subclinical gut inflammation has been described in up to two-thirds of patients with spondyloarthropathies (SpA). Arthritis represents an extra-intestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease (IBD), Whipple’s disease, Behcet’s disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis. Moreover about two-thirds of nonsteroidal anti-inflammatory drug users demonstrate intestinal inflammation. Arthritis may manifest as a peripheral or axial arthritis. The spondyloarthropathy family consists of the following entities: ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis. This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti-inflammatory drugs users

Clinical implications of mucosal healing in the management of patients with inflammatory bowel disease

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