Background: The therapeutical targets proposed for the treatment of Inflammatory Bowel Diseases (IBDs) are rapidly evolving. Within the context of Ulcerative Colitis (UC), the STRIDE-2 guidelines set the endoscopic remission as the long-term goal, as this parameter can significantly reduce negative outcomes (defined as flare-ups, hospitalizations and surgeries). Recently, however, the International Organization for the Study of Inflammatory Bowel Diseases (IOBDs) have introduced the concept of Disease Clearance (DC). DC is a composite parameter of clinical, endoscopic and histological remission, which seems to be more predictive at reducing long-term negative outcomes compared to endoscopic remission alone. Inside this context, preliminary data suggested that biologic drugs (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) and small molecules (Tofacitinib) - currently approved for UC treatment - have all the ability to induce DC, although it is unclear which of these drugs are more effective in achieving this therapeutic goal. Objective: This study aims to determine the percentage of UC patients at the Gastroenterology Unit of the University Hospital of Padua who achieve DC while undergoing advanced treatments. The second aim of this study is to identify which advanced therapy is more effective in achieving DC in the mentioned above group of patients. Materials and methods: Adult patients with UC undergoing advanced therapies treatment from 2011 to 2023 and who have endoscopic and histological examinations performed before and after the therapy initiation were enrolled in this study. Patients who had previously undergone surgery were excluded from the study. Patients were selected using an internal database, and the clinical information was collected reading their medical records. The DC for UC was defined as the simultaneous presence of clinical remission (partial Mayo Score = 0), endoscopic remission (endoscopic Mayo Score = 0), and histological remission (Geboes Score ≤ 1), and patients were monitored during long-term follow-up (≥ 12 months). Results: DC was achieved by 6.3% of patients at 12 months and in 26.7% of patients under advanced therapy in the (median follow-up time of 2,4 years). Among the advanced therapies, Tofacitinib (38.5%) and Golimumab (35.5%) were found to be more effective in inducing DC, although no significant differences were observed compared to other drugs. Furthermore, no baseline parameters predictive of achieving DC were identified: prior therapeutic failures or more severe disease at diagnosis did not reduce the chances of achieving DC. Conclusions: Although DC represents a therapeutic goal capable of reducing long-term negative outcomes, it is achieved in a low percentage of patients. Moreover, there appear to be no significant differences in efficacy between advanced therapies, nor baseline clinical parameters have been found to increase the chance of achieving DC. Consequently, DC may not represent an effective parameter for guiding clinical decisions during UC therapy - excessively raising the bar for therapeutic objectives - but rather an additional parameter of deep remission. Further studies are needed to evaluate a potential modification of the current definition of DC, including the parameter of molecular remission.
Presupposti dello studio: Gli obiettivi terapeutici proposti per il trattamento delle Malattie Infiammatorie Croniche Intestinali (MICI) sono in rapida evoluzione. In particolare, nel contesto della Rettocolite Ulcerosa (RCU), le linee guida STRIDE-2 pongono come obiettivo a lungo termine la remissione endoscopica, parametro capace di ridurre in maniera significativa gli outcomes negativi (riacutizzazioni, ospedalizzazioni e interventi chirurgici). Recentemente, tuttavia, è stato introdotto il concetto di Disease Clearance (DC) dall’International Organization for the Study of Inflammatory Bowel Diseases (IOBDs), un parametro composito di remissione clinica, endoscopica ed istologica, che sembrerebbe in grado di ridurre a lungo termine gli outcomes negativi in maniera significativamente migliore rispetto alla sola remissione endoscopica. In questo contesto, dati preliminari suggeriscono che i farmaci biologici (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) e le small molecules (Tofacitinib), attualmente approvati per il trattamento della RCU, sono in grado di indurre la DC, sebbene non sia chiaro quale tra questi farmaci sia più efficace per raggiungere questo obiettivo terapeutico. Scopo dello studio: Questo studio mira ad individuare la percentuale di raggiungimento della DC di un campione di pazienti con RCU in terapia con farmaco avanzato (farmaci biologici o small molecule) trattati presso l’UOC di Gastroenterologia dell’Azienda Ospedale Università di Padova. Il secondo obiettivo dello studio è identificare quale tra i farmaci avanzati utilizzati sia più efficace nel raggiungere la suddetta DC. Materiali e metodi: Sono stati arruolati pazienti maggiorenni con RCU in terapia con farmaci avanzati dal 2011 al 2023, con esami endoscopici e istologici eseguiti prima e dopo l’inizio della terapia. I pazienti precedentemente operati sono stati esclusi dallo studio. I suddetti pazienti sono stati selezionati utilizzando un database ad uso interno e i dati clinici sono stati raccolti tramite le cartelle cliniche degli stessi. La DC per la RCU è stata definita come la presenza contemporanea di remissione clinica (partial Mayo Score =0), endoscopica (endoscopic Mayo Score =0) e istologica (Geboes Score ≤1), ed i pazienti sono stati monitorati durante un follow-up a lungo termine (≥12 mesi). Risultati: la DC è stata ottenuta in terapia con farmaci avanzati nel 6,3% dei pazienti a 12 mesi e nel 26,7% dei pazienti nel corso del follow-up (follow-up mediani di 2,3 anni). Tra i farmaci avanzati, Tofacitinib (38,5%) e Golimumab (35,5%) si sono dimostrati più efficaci nell’indurre DC, sebbene non siano state rivelate differenze significative rispetto agli altri trattamenti. Inoltre, non si sono identificati parametri basali predittivi di ottenimento di DC: la presenza di precedenti fallimenti terapeutici o una malattia più grave alla diagnosi, infatti, non sembrano ridurre le possibilità di ottenere DC nei pazienti in terapia. Conclusioni: Nonostante la DC rappresenti un obiettivo terapeutico capace di ridurre gli outcomes negativi a lungo termine, questa viene raggiunta in una bassa percentuale di pazienti. Inoltre, non sembrano esserci differenze significative di efficacia fra farmaci avanzati, né tantomeno sono stati individuati parametri clinici basali che possano favorire la DC. Di conseguenza, la DC potrebbe non rappresentare un target raggiungibile su cui basare le decisioni cliniche durante la terapia della RCU, alzando eccessivamente l’asticella degli obiettivi terapeutici, ma solo un parametro addizionale di remissione profonda. Ulteriori studi sono necessari per valutare una eventuale modifica della definizione attuale di DC con l’aggiunta, eventualmente, del target di remissione molecolare.
Disease Clearance nelle IBD: Un Possibile Target da Raggiungere?
FRASSON, LEONARDO
2023/2024
Abstract
Background: The therapeutical targets proposed for the treatment of Inflammatory Bowel Diseases (IBDs) are rapidly evolving. Within the context of Ulcerative Colitis (UC), the STRIDE-2 guidelines set the endoscopic remission as the long-term goal, as this parameter can significantly reduce negative outcomes (defined as flare-ups, hospitalizations and surgeries). Recently, however, the International Organization for the Study of Inflammatory Bowel Diseases (IOBDs) have introduced the concept of Disease Clearance (DC). DC is a composite parameter of clinical, endoscopic and histological remission, which seems to be more predictive at reducing long-term negative outcomes compared to endoscopic remission alone. Inside this context, preliminary data suggested that biologic drugs (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) and small molecules (Tofacitinib) - currently approved for UC treatment - have all the ability to induce DC, although it is unclear which of these drugs are more effective in achieving this therapeutic goal. Objective: This study aims to determine the percentage of UC patients at the Gastroenterology Unit of the University Hospital of Padua who achieve DC while undergoing advanced treatments. The second aim of this study is to identify which advanced therapy is more effective in achieving DC in the mentioned above group of patients. Materials and methods: Adult patients with UC undergoing advanced therapies treatment from 2011 to 2023 and who have endoscopic and histological examinations performed before and after the therapy initiation were enrolled in this study. Patients who had previously undergone surgery were excluded from the study. Patients were selected using an internal database, and the clinical information was collected reading their medical records. The DC for UC was defined as the simultaneous presence of clinical remission (partial Mayo Score = 0), endoscopic remission (endoscopic Mayo Score = 0), and histological remission (Geboes Score ≤ 1), and patients were monitored during long-term follow-up (≥ 12 months). Results: DC was achieved by 6.3% of patients at 12 months and in 26.7% of patients under advanced therapy in the (median follow-up time of 2,4 years). Among the advanced therapies, Tofacitinib (38.5%) and Golimumab (35.5%) were found to be more effective in inducing DC, although no significant differences were observed compared to other drugs. Furthermore, no baseline parameters predictive of achieving DC were identified: prior therapeutic failures or more severe disease at diagnosis did not reduce the chances of achieving DC. Conclusions: Although DC represents a therapeutic goal capable of reducing long-term negative outcomes, it is achieved in a low percentage of patients. Moreover, there appear to be no significant differences in efficacy between advanced therapies, nor baseline clinical parameters have been found to increase the chance of achieving DC. Consequently, DC may not represent an effective parameter for guiding clinical decisions during UC therapy - excessively raising the bar for therapeutic objectives - but rather an additional parameter of deep remission. Further studies are needed to evaluate a potential modification of the current definition of DC, including the parameter of molecular remission.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/66802