Loftus, Edward V

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.

Background: : The isolated effect of vedolizumab on increased postoperative complications remains debated, similar to the controversial data on anti-TNF and postoperative complications. Objective: : To determine the risk of vedolizumab on postoperative complications. Method:: A review of the literature available to date on studies comparing postoperative outcomes in vedolizumab-treated versus non-vedolizumab-treated patients was performed. Studies were stratified by those which combined all inflammatory bowel disease together, those specifically focusing on Crohn’s disease or ulcerative colitis individually, and those which included pediatric patients alone. Results:: The data remains controversial in both the adult and pediatric literature regarding the association of vedolizumab and increased postoperative complications. The strongest association between vedolizumab and an increased risk of postoperative infectious complications seems to be in the Crohn’s disease literature. Conclusion:: Vedolizumab may be associated with an increased risk of postoperative infectious complications in Crohn’s disease, but the literature remains controversial due to difficulty in isolating the effect of the biologic alone in a chronically ill, heterogeneous patient population who are on multiple medications including corticosteroids.

Abstract Background PYRAMID was an international multicenter, noninterventional, postmarketing registry assessing long-term safety and effectiveness of adalimumab (Humira), as used in routine clinical practice. Methods Adult patients with moderately to severely active Crohn’s disease with or without prior adalimumab experience were enrolled in the registry and followed for up to 6 years. Effectiveness measurements included the Physician’s Global Assessment (PGA, a composite of Harvey Bradshaw Index [HBI] and rectal bleeding score), clinical remission (HBI < 5), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Work Productivity and Activity Impairment (WPAI) questionnaire. Data were reported for adalimumab-naïve patients and analyzed by baseline immunomodulator use and disease duration. Results This study evaluated 2057 adalimumab-naïve patients. Mean PGA improved from 7.5 (baseline) to 3.9 (year 1) and 3.3 (year 6). The proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates; patients with disease duration <2 years achieved numerically higher HBI remission rates than patients with longer disease duration. Patient-reported SIBDQ and WPAI scores improved at year 1; all WPAI subscore improvements were clinically meaningful (≥7% point change) at year 1 and maintained through year 6. Serious infections were reported in 11.1% of patients; incidence rates of malignancies, lymphoma, and demyelinating disorders were low. Conclusion Adalimumab therapy, as used in routine clinical practice, improved physician-reported and patient-reported disease outcomes and remission rates for up to 6 years. No new safety signals were observed.

Background: Although inflammatory bowel disease (IBD) has been more predominant in white populations, an increasing incidence of IBD in nonwhites has been reported. We sought to evaluate the incidence rates and temporal trends of IBD by race and ethnicity. Methods: The resources of the Rochester Epidemiologic Project were used to identify 814 county residents newly diagnosed with IBD from 1970 through 2010. Race was categorized into whites and nonwhites. Ethnicity was categorized into Hispanic and non-Hispanic. Incidence rates were estimated and adjusted for age and sex to the 2010 United States (US) population. Trends in incidence rates were evaluated by Poisson regression. Results: The adjusted annual incidence rate of IBD for whites was 21.6 cases per 100,000 person-years [95% confidence interval (CI), 20.0–23.1] and for nonwhites it was 13 per 100,000 (95% CI, 8.3–17.5). The incidence rates for whites and nonwhites increased by 39% and 134%, respectively, from 1970 through 2010. The adjusted annual incidence rate of IBD for Hispanics was 15 cases per 100,000 person-years (95% CI, 6.3–23.6) and for non-Hispanics was 20 per 100,000 (95% CI, 18.5–21.6). The incidence rate for Hispanics decreased by 56%, while the rate for non-Hispanics increased by 33%, from 1985 through 2010. In a Poisson regression, white race ( p < 0.0001), a later year of diagnosis ( p < 0.001), male sex ( p < 0.001) and younger age ( p = 0.009) were significantly associated with a higher incidence rate of IBD. Conclusions: There were significant racial and ethnic differences in the incidence and temporal trends of IBD over the last four decades in this US population-based cohort.

Abstract Background Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), and CDI often precipitates IBD exacerbation. Because CDI cannot be distinguished clinically from an IBD exacerbation, management is difficult. We aimed to assess factors associated with adverse outcomes in IBD with CDI, including the role of escalating or de-escalating IBD therapy and CDI treatment. Methods Records for patients with IBD and CDI from 2008 to 2013 were abstracted for variables including IBD severity before CDI diagnosis, CDI management, subsequent IBD exacerbation, CDI recurrence, and colon surgery. Colon surgery was defined as resection of any colonic segment within 1 year after CDI diagnosis. Results We included 137 IBD patients (median age, 46 years; 55% women): 70 with ulcerative colitis (51%), 63 with Crohn’s disease (46%), and 4 with indeterminate colitis (3%). Overall, 70% of CDIs were mild-moderate, 14% were severe, and 15% were severe-complicated. Clostridium difficile infection treatment choice did not vary by infection severity (P = 0.27). Corticosteroid escalation (odds ratio [OR], 5.94; 95% confidence interval [CI], 2.03–17.44) was a positive predictor of colon surgery within 1 year after CDI; older age (OR, 0.09; 95% CI, 0.01–0.44) was a negative predictor. Modifying the corticosteroid regimen did not affect CDI recurrence or risk of future IBD exacerbation. Adverse outcomes did not differ with CDI antibiotic regimens or biologic or immunomodulator regimen modification. Conclusions Corticosteroid escalation for IBD during CDI was associated with higher risk of colon surgery. Type of CDI treatment did not influence IBD outcomes. Prospective studies are needed to further elucidate optimal management in this high-risk population.