Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

Perception and clinical decisions from inflammatory bowel diseases' specialists towards positioning of new therapies in Crohn's disease and ulcerative colitis: A national web-based survey from the Brazilian IBD study group (GEDIIB).

BACKGROUND: In the last decade, new therapies with different mechanisms of action have been approved for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Due to the lack of comparative head-to-head trials, the ideal positioning of agents as the most appropriate first- or second-line therapies remains to be defined. OBJECTIVE: This survey aimed to evaluate the perception and decisions of Brazilian Inflammatory Bowel Diseases (IBD) specialists in positioning of new therapies (vedolizumab [VEDO], ustekinumab [UST] and tofacitinib [TOFA]) in the management of IBD in different clinical scenarios. METHODOLOGY: An anonymous national web-based questionnaire was used to determine the positioning of treatment options in different clinical scenarios (using Google Forms platform), which involved different age ranges, phenotypes, clinical situations and previous exposure to anti-TNF agents (14 scenarios for CD and 10 scenarios for UC). In CD, physicians could choose between UST or VEDO, whilst in UC, between UST, VEDO or TOFA. Six reasons for the specific choice were proposed, such as mechanism of action, safety, method of administration or onset of action. Statistical analysis was carried out with chi-square and t-tests. RESULTS: A total of 150 out of 672 GEDIIB IBD specialists (22.32%) responded to the survey. In CD scenarios, UST was the most dominant choice (11/14 scenarios), with VEDO dominating only 3 clinical situations. In UC scenarios, VEDO was the dominant choice (8/10), with UST being chosen for scenarios that included extraintestinal manifestations. Among the reasons for specific choices, the most commonly chosen were the higher efficacy due to the intrinsic mechanism of action and safety profile. CONCLUSIONS: UST was the dominant choice as compared to VEDO in CD in most scenarios, especially due to its mechanism of action and safety. VEDO was the dominant choice as compared to UST and TOFA in UC scenarios, mainly for reasons also related to its mechanism of action and safety profile. Comparative studies including patient outcomes are needed to better define the positioning of new IBD therapeutic options in our country.

Medical Therapy in Chronic Refractory Ulcerative Colitis: When Enough Is Enough.

Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small molecules, a subset of medically refractory patients still requires colectomy. Recent population-based studies demonstrate a trend toward a decrease in the rates of surgery for UC patients in the biological era, although the potential of disease modification with these agents is still debated. As the concept of irreversible bowel damage is underexplored in UC, refractory patients can be exposed to multiple treatments losing optimal timing for surgery and further developing complications such as dysplasia/cancer, dysmotility, microcolon, and other functional abnormalities. This review aims to discuss the concept of disease progression in UC, explore the limitations of medical treatment in refractory UC patients, and propose the application of a three-step algorithm that allows timely indication for surgery in clinical practice.

Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: A Systematic Review.

BACKGROUND & AIMS: The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean. METHODS: We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn's disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis. RESULTS: The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991-1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990-2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012-2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001-2003 and 6.2% in 2004-2014. CONCLUSIONS: In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.

A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy.

Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often involves the use of anti-tumor necrosis factor alpha (TNF-α) agents. Although very effective, theses biologics place the patient at increased risk for developing infections and lymphomas, the latter especially when in combination with thiopurines. Appropriate patient selection, counseling, and education are all important features for the successful use of anti-TNF-α therapy. A thorough history to rule-out contraindications of this therapy and emphasis on monitoring guidelines are important steps preceding administration of anti-TNF-α agents. This therapy should only be considered if a recent evaluation has established that the patient has active IBD. In addition, it is important to exclude disease mimickers. Anti-TNF-α agents have been considered to present a globally favorable benefit/risk ratio. However, it is important that in routine practice, initiation of anti-TNF-α therapy be carefully discussed with the patient, extensively explaining the potential benefits and risks of such treatment. Prior to starting anti-TNF-α therapy, the patients need to be screened for latent tuberculosis, hepatitis B virus infection, and (usually) hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should be evaluated and updated prior to the commencement of anti-TNF-α therapy. Ordinarily, immunization in adult patients with IBD should not deviate from recommended guidelines for the general population. With the exception of live vaccines, immunizations can be safely administered in patients with IBD, even those on immunosuppressants or biologics. The purpose of this review is providing an overview of appropriate steps to prepare patients with IBD for anti-TNF-α therapy.

Predictive factors of response to infliximab therapy in Brazilian inflammatory bowel disease patients.

Background: Biological therapies have revolutionized the treatment of patients with inflammatory bowel disease (IBD). Infliximab (IFX) has been shown to be effective in inducing and maintaining remission in patients with Crohn's disease and ulcerative colitis. However, about one-third of the patients are primary non-responders, and up to half can lose response over time. Hence, it is important to assess which factors are related to treatment failure. Objectives: We aimed to identify factors predicting clinical and endoscopic remission with IFX treatment during maintenance therapy in a Brazilian IBD referral center. Design: We conducted a cross-sectional study to describe demographic, clinical, and IBD therapy-related characteristics of IBD patients treated with IFX for at least 6 months in a Brazilian referral center. Subsequently, we evaluated factors associated with clinical and endoscopic remission (primary and secondary outcomes, respectively). Methods: We used descriptive statistics to summarize the essential demographic and clinical characteristics of the population. The association of sociodemographic and clinical variables with outcomes was analyzed using multivariable logistic regression. Results: A total of 131 IBD patients (the mean age 41.7 years) were enrolled in this study. Clinical and endoscopic remission were observed in 79.4% and 58.2% of the patients, respectively. In the multivariable analysis, IFX therapy duration and higher albumin levels increased the likelihood of clinical remission, while previous surgery decreased its chance. Prior use of adalimumab and higher C-reactive protein levels reduced the likelihood of endoscopic remission. Conclusion: In summary, this study has enhanced our understanding of the predictive factors of treatment response to IFX in a well-characterized Brazilian IBD population. Trial registration: 4.254.501 and 2.903.748.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

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.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

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.

How to manage inflammatory bowel disease during the COVID-19 pandemic: A guide for the practicing clinician.

Managing inflammatory bowel disease (IBD) during the coronavirus disease 2019 (COVID-19) pandemic has been a challenge faced by clinicians and their patients, especially concerning whether to proceed with biologics and immunosuppressive agents in the background of a global outbreak of a highly contagious new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). The knowledge about the impact of this virus on patients with IBD, although it is still scarce, is rapidly evolving. In particular, concerns surrounding medications' impact for IBD on the risk of acquiring SARS-CoV-2 infection or developing COVID-19, and potentially exacerbate viral replication and the COVID-19 course, are a current thinking of both practicing clinicians and providers caring for patients with IBD. Managing patients with IBD infected with SARS-CoV-2 depends on both the clinical activity of the IBD and the occasional development and severity of COVID-19. In this review, we summarize the current data regarding gastrointestinal involvement by SARS-CoV-2 and pharmacologic and surgical management for IBD concerning this infection, and the COVID-19 impact on both the patient's psychological functioning and endoscopy services, and we concisely summarize the telemedicine roles during the COVID-19 pandemic.

Risk stratification and geographical mapping of Brazilian inflammatory bowel disease patients during the COVID-19 outbreak: Results from a nationwide survey.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is still evolving globally, and Brazil is currently one of the most affected countries. It is still debated whether patients with inflammatory bowel disease (IBD) are at a higher risk for developing COVID-19 or its complications. AIM: To assess geographical distribution of IBD patients at the highest risk and correlate these data with COVID-19 mortality rates in Brazil. METHODS: The Brazilian IBD Study Group (Grupo de Estudos da Doença Inflamatória Intestinal do Brasil) developed a web-based survey adapted from the British Society of Gastroenterology guidelines. The included categories were demographic data and inquiries related to risk factors for complications from COVID-19. Patients were categorized as highest, moderate or lowest individual risk. The Spearman correlation test was used to identify any association between highest risk and mortality rates for each state of the country. RESULTS: A total of 3568 patients (65.3% females) were included. Most participants were from the southeastern and southern regions of Brazil, and 84.1% were using immunomodulators and/or biologics. Most patients (55.1%) were at moderate risk, 23.4% were at highest risk and 21.5% were at lowest risk of COVID-19 complications. No association between the proportion of IBD patients at highest risk for COVID-19 complications and higher mortality rates was identified in different Brazilian states (r = 0.146, P = 0.467). CONCLUSION: This study indicates a distinct geographical distribution of IBD patients at highest risk for COVID-19 complications in different states of the country, which may reflect contrasting socioeconomic, educational and healthcare aspects. No association between high risk of IBD and COVID-related mortality rates was identified.

Performance of two commercial ELISAs for detecting IgA anti-human and anti-guinea pig tissue transglutaminase antibodies.

BACKGROUND: Sensitivity and specificity of anti-human tissue transglutaminase antibodies (anti-htTGA) seem to be superior to those of anti-tissue transglutaminase of guinea pig (anti-gptTGA) for screening patients with celiac disease (CD), but there are still controversies. The aim of this study was to evaluate the performance of two INOVA ELISA kits to detect IgA anti-htTGA and anti-gptTGA in patients with and without CD. METHODS: The study groups were comprised of 49 anti-endomysial antibody (EMA)-positive untreated-CD, and 123 controls (EMA-negative treated CD, EMA-negative chronic diarrhea, autoimmune hepatitis, inflammatory bowel disease and healthy people). RESULTS: The agreement between the two ELISAs was statistically significant in all study groups and there was no significant difference between them (92.7% agreement; kappa = 0.70; kappa p = 0.001; McNemar p = 1). All patients with serum reactivity of more than 100 units had histologic diagnosis of CD. In seven of 10 patients with treated-CD who had control biopsies, villous atrophy was still present in four who tested positive by both kits. Two of three celiacs with histologic remission tested positive for both anti-tTGA. CONCLUSIONS: the anti-gptTGA and anti-htTGA determination were equally efficient in identifying patients with untreated-CD with high titers of EMA. Whatever the anti-tTGA ELISA used, the reactivity above 100 units was always related to active CD diagnosed by histologic alterations in intestinal biopsies. The anti-tTGA reactivity by both kits was not only similar in determining histologic activity in the follow-up of CD after a gluten free diet, but also in identifying positive sera from the control groups, regardless if CD has been confirmed by duodenal biopsies.

Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance.

The world is fighting the COVID-19 outbreak and health workers, including inflammatory bowel diseases specialists, have been challenged to address the specific clinical issues of their patients. We hereby summarize the current literature in the management of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic era that support the rearrangement of our IBD unit and the clinical advice provided to our patients.

Recovery from COVID-19 Pneumonia in a Patient with Acute Severe Colitis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has increased concern regarding SARS-CoV-2 infection in inflammatory bowel disease (IBD) patients, especially those on immunosuppressive therapies or with active disease. There are limited reports describing the clinical features of COVID-19 in an IBD population, and the impact of immunosuppression on the severity of the infection remains unclear. CASE REPORT: A 33-year-old female patient with a long history of ulcerative colitis, poorly controlled, was admitted with COVID-19 a few days after being discharged from the hospital for treatment of acute severe ulcerative colitis. High-risk factors for COVID-19 complications, i.e., high-dose steroids (40 mg prednisone) and severe active disease, were present at admission. Despite the development of extensive pulmonary involvement, the patient had a favorable outcome. DISCUSSION: Management of IBD patients during the COVID-19 pandemic has been challenging. Measures to minimize the potential risk of SARS-CoV-2 infection, including strict social distancing and self-isolation, in the IBD population have been recommended, especially for high-risk patients. Although steroid tapering and persistence of biologics are advised by professional groups, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined.

BIOLOGICAL THERAPY PENETRATION FOR INFLAMMATORY BOWEL DISEASE IN LATIN AMERICA: CURRENT STATUS AND FUTURE CHALLENGES.

BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.

Conventional therapy for moderate to severe inflammatory bowel disease: A systematic literature review.

BACKGROUND: Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease (MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes. AIM: To investigate the effectiveness of conventional therapy for MS-IBD. METHODS: A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-aminosalicylic acid (5-ASA) derivatives (mesalazine and sulfasalazine) and immunosuppressants [azathioprine (AZA), methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine (6-MP)] were considered conventional therapy. The exclusion criteria were sample size below 50; narrative reviews; specific subpopulations (e.g., pregnant women, comorbidities); studies on postoperative IBD; and languages other than English, Spanish, French or Portuguese. The primary outcome measures were clinical remission (induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: The search strategy identified 1995 citations, of which 27 were considered eligible (7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected (AZA and 6-MP showed no advantage over placebo, MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials (RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing, one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence. CONCLUSION: High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.

VEDOLIZUMAB IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASES: A BRAZILIAN OBSERVATIONAL MULTICENTRIC STUDY.

BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn's disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

Ulcerative colitis - treatment with biologicals.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

TOFACITINIB IN THE MANAGEMENT OF ULCERATIVE COLITIS REFRACTORY TO ANTI-TNF AND ANTI-INTEGRIN THERAPIES.

Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

ADALIMUMAB FOR ULCERATIVE COLITIS: RESULTS OF A BRAZILIAN MULTICENTER OBSERVATIONAL STUDY.

BACKGROUND: Adalimumab is a monoclonal antibody, tumor necrosis factor-alpha (TNFα) inhibitor that has efficacy for inducing and maintaining remission in moderate-to-severe ulcerative colitis. Real world studies with adalimumab in Latin American ulcerative colitis patients are scarce. OBJECTIVE: To assess the clinical remission rates in induction and maintenance with adalimumab therapy in ulcerative colitis. METHODS: Observational, multicenter and retrospective study on a case series of patients with moderate-to-severe ulcerative colitis under adalimumab therapy. The variables analyzed were: demographic data, previous infliximab status, concomitant drugs, the Montreal Classification, disease activity (Mayo score) at weeks 0, 8, 26 and 52, or until the last follow-up. Clinical remission was defined as a partial Mayo score ≤2 and Last observation carried forward (LOCF) and Non responder imputation (NRI) analysis were used. RESULTS: Thirty-six patients were included in the study. With LOCF analysis, remission rates at weeks 8, 26 e 52 were of 41.7%, 47.2% and 47.2%, respectively. With NRI analysis, remission rates at weeks 8, 26 and 52 were of 41.7%, 41.7% and 27.8%, respectively. CONCLUSION: Adalimumab was effective in the treatment of moderate-to-severe ulcerative colitis. Clinical remission was observed in approximately 40% of the patients at weeks 8 and 26, and in almost a quarter of the patients after 1 year of follow up.