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BACKGROUND AND AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. METHODS: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. RESULTS: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. CONCLUSIONS: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups.
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Colitis Ulcerosa , Piperidinas , Pirimidinas , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Inducción de Remisión , Reducción Gradual de Medicamentos , Interrupción del Tratamiento , Resultado del TratamientoRESUMEN
The two major forms of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions characterised by an increased production of pro-inflammatory cytokines that act as critical drivers of intestinal inflammation. Anti-cytokine therapy has been shown to improve clinical outcomes in IBD. Janus kinases (JAKs) are tyrosine kinases that bind different intracellular cytokine receptors, leading to phosphorylation of signal transducer and activation of transcription molecules implicated on targeted gene transcription. Four isoforms of JAKs have been described: JAK1, JAK2, JAK3 and TYK2. Oral JAK inhibitors (JAKi) have been developed as synergic anti-cytokine therapy in IBD, showing different selectivity towards JAK isoforms. Tofacitinib, a pan-JAK inhibitor, has been recently approved for the treatment of moderate-to-severe UC. With the aim of improving the benefit: risk ratio of this drug class, several second-generation subtype-selective JAKi are under development. However, whether selective inhibition of JAK isoforms is associated with an increased clinical efficacy and/or a better safety profile remains debatable. The aim of this review is to critically review the preclinical and clinical data for the differential selectivity of JAK inhibitors and to summarise the potential clinical implications of the selective JAK inhibitors under development for UC and CD.
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Inmunosupresores/uso terapéutico , Inmunoterapia/métodos , Enfermedades Inflamatorias del Intestino/terapia , Quinasas Janus/sangre , Biomarcadores/sangre , Citocinas/sangre , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Quinasas Janus/efectos de los fármacosRESUMEN
BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn's and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study's risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3â87.0; I2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0â45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%â82.9%; I2 = 77%). CONCLUSIONS: In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Fármacos Gastrointestinales/administración & dosificación , Quimioterapia de Mantención/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy. The treat to target approach possibly correlates with minor risk for complications associated with IBD, specially surgery and cancer. The most studied inflammatory pathway in IBD, is described to be dependent of the pro-inflammatory cytokine tumor necrosis factor-alfa (TNF-α), and compose the first line studies for development of biological drugs, in this case, targeting specifically the action of TNF-α. Even though, the use of anti-TNFs drugs are associated with improvement of the inflammation in some patients, a great portion do not respond at first or lose response over time. These findings made clear about the possibility of other mechanisms involved in perpetuating the chronic inflammatory state. Many years of intensive research have led to the identification of different inflammatory pathways that form the basis of the intensive drug development that we are experiencing today. These novel drugs include agents that target leukocyte trafficking, Interleukin (IL) 23, Janus kinases (JAK), Sphingosine 1 phosphate (S1P) and Smad7, an inhibitor of the immunosuppressive cytokine transforming growth factor ß1 (TGF-ß1). In this manuscript, we aim to review the most promising late-stage drug candidates for the treatment of IBD.
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Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Animales , Humanos , Inflamación/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC. Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy. Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.
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Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients. Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab. Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery. Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD.
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BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.
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Colitis Ulcerosa , Neoplasias Colorrectales , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Enfermedad de Crohn/diagnóstico , Brasil , Enfermedades Inflamatorias del Intestino/complicaciones , Inflamación , Neoplasias Colorrectales/complicacionesRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Enfermedad de Crohn/terapia , Enfermedad de Crohn/tratamiento farmacológico , Consenso , Brasil , Colitis Ulcerosa/tratamiento farmacológicoRESUMEN
In the treat-to-target era, endoscopy has become the backbone of the assessment of remission, defined as mucosal healing, in inflammatory bowel disease (IBD) patients. Current recommendations indicate that endoscopic procedures should be performed with high-definition white-light endoscopy (HD-WLE), as it guarantees the best possible visualization of the mucosa. With respect to endoscopic surveillance, the preventive strategy for dysplasia and colorectal cancer (CRC) in long-standing IBD, is the use of dye-chromoendoscopy (DCE), which enhances the mucosal pattern of the colonic walls. DCE has been established as the gold standard for dysplasia detection and is at present incorporated in all international guidelines. Over the past years, novel technologies, such as high-definition endoscopic imaging, and optical and digital enhancement tools have revolutionized the quality and level of fine details of vascular and mucosal patterns. These endoscopic images have the ambition to reflect histological changes for suspected neoplastic lesions and inflammation or healing and are emerging as potential alternatives to DCE. Indeed, the comparison of DCE with high-definition imaging is an open issue that deserves further investigation. We aimed to examine and summarize the technical aspects and the current evidence on endoscopic technologies with a specific focus on the surveillance in IBD patients.
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BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. RESULTS: GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. CONCLUSIONS: In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis.
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Enfermedades Inflamatorias del Intestino , Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/etiología , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiología , Neoplasias Gástricas/terapiaRESUMEN
BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract with an increasing incidence in developing countries. PURPOSE: To report clinical and demographic data of CD and UC at a referral center for inflammatory bowel disease (IBD) in São Paulo. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study on adult patients with established IBD. Demographic and clinical data were obtained by medical records analysis from the IBD Outpatient Clinic of EPM-UNIFESP, from October 1997 to October 2017. RESULTS: Of 658 patients included, 355 had UC (54%) and 303 had CD (46%). UC was more prevalent in women than CD (219 [61.7%] vs 152 [50.2%], p=0.003). The median time between the onset of symptoms and diagnosis was 13 (5-38) months, with a longer duration for CD patients. CD mostly affected the ileocolonic location (47.9%). CD patients with stricture, fistula and/or perianal disease (213/303, 70.3%) were younger at diagnosis, had a longer disease duration, higher rates of corticosteroid, immunomodulatory, and biological therapy, hospitalization, and referral to surgery, compared to patients without complication. Extensive colitis was the most common extension of UC (50.6%), which was more frequently associated with younger age at diagnosis, hepatobiliary disease, increased need for hospitalization, higher use of immunomodulatory, and biologic therapy, compared to patients with less extensive disease. In the last 5 years, CD patients were more frequently on biologic and/or immunomodulatory (70.9%) therapy, and UC patients often received salicylates (78.1%) and immunomodulatory (28.1%) treatments. There was a consistent reduction in salicylate usage for CD in the last 5 years compared to the total period of follow-up. CONCLUSION: Despite the increasing incidence, we highlight the diagnostic delay and a more complicated CD and extensive UC in this cohort, reflecting a high need for immunomodulatory and biological treatment, hospitalization, and surgery.
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BACKGROUND: The management of chronic conditions, above all rheumatic disease and diabetes, now incorporates a "treat to target" strategy where treatment aims to achieve objective outcomes. This is applicable in ulcerative colitis (UC) as well. Targets are demonstrated to prevent endorgan dysfunction, specifically bowel damage and its complications, and lastly colorectal cancer. Recently, the scientific community has tried to define further targets beyond those currently recommended, namely mucosal healing and clinical remission. Studies that prospectively investigated this approach in UC are scanty and a treat-to-target (T2T) algorithm is not routinely used in daily clinical practice. OBJECTIVE: We aim to review current evidence on T2T in UC and discuss its adoption in routine clinical practice as well as in clinical trials. METHODS: A PubMed search was conducted in February 2020 to identify published papers investigating targets' achievement rates in UC. RESULTS: Different targets can be achieved through approved drugs for mild to moderate UC; histological remission is emerging as a robust target with respect to long-term outcomes. CONCLUSION: Further studies to compare a T2T strategy with the traditional care are needed, particularly in the mild to moderate spectrum of disease.
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Colitis Ulcerosa , Colitis Ulcerosa/tratamiento farmacológico , Humanos , Inducción de Remisión , Cicatrización de HeridasRESUMEN
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. In the last few years, the development of biological agents targeting cytokines and receptors involved in IBD pathogenesis has led to better outcomes and has improved the course of the disease. Despite their effectiveness, drugs such as tumor necrosis factor (TNF) inhibitors, anti-Interleukin-12/23 and anti-integrins, do not induce a response in about one-third of patients, and 40% of patients lose response over time. Therefore, more efficient therapies are required. Recent studies showed that TL1A (Tumor necrosis factor-like cytokine 1A) acts as a regulator of mucosal immunity and participates in immunological pathways involved in the IBD pathogenesis. In this review article, we analyze the role of TL1A as a new potential target therapy in IBD patients.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/antagonistas & inhibidores , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
INTRODUCTION: Janus kinases inhibitors (JAKi) are new small molecules recently introduced in the armamentarium of treatments for Inflammatory Bowel Disease (IBD). Janus Kinases (JAK) are tyrosine kinases that act by linkage with different intracellular receptors, regulating cytokines gene transcription implicated in the inflammatory burden seen in IBD patients. AREAS COVERED: A comprehensive literature search was performed to retrieve studies on JAKi and IBD to discuss the latest developments and how the selectivity of these drugs is changing the natural course of IBD. EXPERT OPINION: Available data on efficacy and safety of JAKi in IBD are highly encouraging and because of their selectivity, these drugs might become among the foremost options in the treatment algorithm.
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Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 3/antagonistas & inhibidores , Naftiridinas/uso terapéutico , Nitrilos/uso terapéutico , Piridinas/uso terapéutico , Transducción de Señal , TYK2 Quinasa/antagonistas & inhibidores , Triazoles/uso terapéuticoRESUMEN
Proposed treatment targets for the management of inflammatory bowel disease (IBD) have moved beyond symptomatic improvement towards more objective end points, such as healing of the intestinal mucosa. This treat-to-target approach has been associated with improved disease outcomes such as diminished bowel damage, surgery and hospitalizations. Many patients with IBD require biologic therapy to achieve and maintain clinical and endoscopic remission, and antitumour necrosis factor antibodies remain the first-line biologic therapy in most areas of the world. Unfortunately, up to one-third of patients receiving this treatment are primary non-responders, and some patients that show an initial response can also lose response over time. Therapeutic drug monitoring (TDM) has been suggested as a useful tool to manage patients on antitumour necrosis factor treatment, including monitoring for dose escalation, de-escalation or to switch treatment. In this Perspective, we aim to summarize evidence and guidelines related to TDM in IBD management and also discuss potential strategies to optimize biologic treatment where TDM is not available.
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Anticuerpos Monoclonales/uso terapéutico , Terapia Biológica , Monitoreo de Drogas/métodos , Enfermedades Inflamatorias del Intestino/terapia , Algoritmos , Biomarcadores/sangre , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/diagnósticoRESUMEN
Introduction: Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are lifetime chronic inflammatory disorders. Over the past few decades, new therapeutic approaches, including early and more effective intervention with immunomodulators and biological agents, increased the possibility of a favorable modification of the natural history of IBD. Despite this progress, there is still a need to explore new therapeutic options.Area covered: Here, we review the literature about the role of therapeutic sphingolipids in inflammatory bowel disease patients.Expert opinion: Despite the great increase of treatment options in the last 20 years, many patients still do not respond to the induction therapy (primary non-responders) or lose response over time (secondary responders). Small-molecule drugs are a promising group of drugs with low molecular weight, an oral route of administration, and low immunogenicity offering several advantages when compared to biologics such as anti-TNFs and anti-integrins. Sphingosine-1-phosphate (S1P) receptor modulators are some among the new small molecules currently under clinical investigation for the treatment of IBD.
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Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Humanos , Esfingolípidos/uso terapéuticoRESUMEN
Introduction: Currently, mucosal healing is considered as a composite treatment end-point in inflammatory bowel disease (IBD) since it has been demonstrated to improve disease-related outcomes. The definition of mucosal healing has evolved and current evidence suggests that in addition to endoscopic healing the achievement of histological remission (HR) represents a potential novel target in the management of IBD in relation to better long-term disease outcomes.Areas covered: We aimed to review the current literature on HR in ulcerative colitis and discuss its limitations and advantages when adopting this potential new target as an ultimate treatment outcome in clinical trials and routine clinical practice.Expert opinion: HR is achievable in UC with different rates in conventional therapies, biological and novel drugs. Targeting HR in UC lowers the risk of hospitalizations, colectomy, and colorectal cancer. HR occurs later than endoscopic remission, longer treatment courses are associated with higher HR assessment. This might imply modifying monitoring time schedules and algorithms. Prospective data are needed to support histological healing as a new treatment target in UC.
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Colitis Ulcerosa/patología , Resultado del Tratamiento , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colonoscopía , Humanos , Mucosa Intestinal/patología , Mesalamina/uso terapéutico , Inducción de RemisiónRESUMEN
INTRODUCTION: Inflammatory bowel diseases (IBD) are chronic and progressive diseases. Long-term complications are demolitive surgery and colon-rectal cancer. A 'treat to target' strategy, in which the treatment aims to achieve objective outcomes, has already been introduced in the management of chronic conditions as rheumatic diseases. This approach is emerging as suitable for ulcerative colitis and Crohn's disease. Targets are predefined therapeutic goals demonstrated to prevent end-organ dysfunction. An optimization or switch of therapy is considered depending on the target's achievement, with regular monitoring. AREAS COVERED: According to the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) indications, mucosal healing and clinical remission are the main targets in IBDs. Histological remission is increasingly being considered as a novel target and has given rise to the new concept of 'disease clearance' which includes clinical, endoscopic and microscopic remission. We aim to review current evidence on the treat-to-target strategy in comparison to a stricter treat-to-clear in the IBD field. EXPERT OPINION: Prospective studies on treat-to-target algorithm are sparse; a treat-to-clear approach is desirable but far from adoption in the daily practice and clinical trials. The ultimate goals of a treat-to-clear strategy differ in UC and in CD, including histological healing and transmural healing, respectively.
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Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Planificación de Atención al Paciente , Algoritmos , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Endoscopía Gastrointestinal , Fármacos Gastrointestinales/uso terapéutico , Humanos , Medición de Resultados Informados por el Paciente , Inducción de Remisión , Cicatrización de HeridasRESUMEN
Crohn's disease is an inflammatory bowel disease that is characterized by chronic inflammation of any part of the gastrointestinal tract, has a progressive and destructive course and is increasing in incidence worldwide. Several factors have been implicated in the cause of Crohn's disease, including a dysregulated immune system, an altered microbiota, genetic susceptibility and environmental factors, but the cause of the disease remains unknown. The onset of the disease at a young age in most cases necessitates prompt but long-term treatment to prevent disease flares and disease progression with intestinal complications. Thus, earlier, more aggressive treatment with biologic therapies or novel small molecules could profoundly change the natural history of the disease and decrease complications and the need for hospitalization and surgery. Although less invasive biomarkers are in development, diagnosis still relies on endoscopy and histological assessment of biopsy specimens. Crohn's disease is a complex disease, and treatment should be personalized to address the underlying pathogenetic mechanism. In the future, disease management might rely on severity scores that incorporate prognostic factors, bowel damage assessment and non-invasive close monitoring of disease activity to reduce the severity of complications.