Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentric Observational Study.

Background: Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods: We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results: A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusions: In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Vedolizumab in Mild-to-Moderate Crohn's Disease Patients Naïve to Biological Therapy: A Multicentric Observational Study.

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.

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system. METHODS: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs. RESULTS: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD (n = 161, 78.5%), nearly half of them (n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab (n = 128, 62.5%) was the most used medication, followed by adalimumab (n = 39, 19.0%). Most patients (n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment. CONCLUSION: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

Factors Predictive of Proximal Disease Extension and Clinical Course of Patients Initially Diagnosed with Ulcerative Proctitis in an IBD Referral Center.

BACKGROUND: This study aims to determine whether risk factors at the time of diagnosis that are found to be predictive of proximal dis- ease extension in ulcerative proctitis (UP) occur in a cohort of Brazilian patients. METHODS: This is a retrospective analysis of data from 97 patients (67% female) with UP (Montreal classification: E1) with at least 12 months of follow-up who were admitted to the Ribeirão Preto Medical School IBD referral center between January 2001 and December 2018. Proximal disease extension, which was defined as E1 progressing to E3 (pancolitis), was evaluated endoscopically during follow-up. RESULTS: A total of 29 (29.9%) patients experienced proximal disease extension. The risk factors at diagnosis associated with proximal disease extension were younger age (<40 years; P = .012), higher Mayo endoscopic score (P < .0001), higher partial Mayo score (P = .0018), and use of oral corticosteroids (P = .0016). During the follow-up period, increased disease relapse rates (P < .0001), immuno- modulators (P = .00014) or the use of biological agents (P = .00037), and colectomy (P = .0002) were all significantly higher among UP patients with proximal disease extension. CONCLUSION: Similar to what has been demonstrated in other studies, Brazilian UP patients with increased clinical and endoscopic sever- ity at the time of diagnosis are likely to evolve with both proximal extension and a more adverse clinical course. Therefore, these patients should be followed-up more carefully.

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases.

BACKGROUND: Since HLA-G is an immune checkpoint molecule and since Crohn's disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension. METHODS: HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA. RESULTS: HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P < 0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P = 0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P = 0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P < 0.0001) than in controls, but no difference was observed between diseases. CONCLUSIONS: Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.