Introduction: Many patients (pts) with ulcerative colitis (UC) initiate conventional therapies (CTs; 5-aminosalicylate, corticosteroids, and thiopurines) but are hesitant to progress to biologic advanced therapies (ATs). Ozanimod (OZA), an oral small molecule AT, is approved in multiple countries for the treatment of moderately to severely active UC. Methods: This analysis of the phase 3 True North (TN) study and subsequent open-label extension (OLE) explored OZA efficacy and durability in AT-naive UC pts inadequately controlled on CTs at TN baseline. AT-naive pts were grouped by baseline endoscopic disease activity as moderate (Mayo endoscopy subscore [MES]=2) or severe (MES=3). In the 10-wk induction period (IP), pts in Cohort 1 (C1) were randomized to OZA 0.92 mg or placebo (PBO) or received open-label OZA in Cohort 2. OZA clinical responders at Week (W) 10 were rerandomized to OZA (OZA/OZA) or PBO (OZA/PBO) during the maintenance period (MP) through W52. W52 OZA/OZA clinical responders continued in the OLE. Clinical and mucosal efficacy endpoints were evaluated at IP W10, MP W52, OLE W46, and OLE W94. Results: A total of 296 moderate and 320 severe pts were included in this analysis. Baseline pt characteristics were similar between groups, but with slightly higher prior immunomodulator use in severe vs moderate pts (Table 1). OZA was more effective than PBO in achieving all efficacy endpoints at W10; treatment differences (OZA [C1] vs PBO) were greater in moderate vs severe pts for all endpoints (Figure 1A). More OZA/OZA vs OZA/PBO pts achieved clinical and mucosal efficacy at W52; treatment differences (OZA/OZA vs OZA/PBO) were slightly greater in moderate vs severe pts for all endpoints except endoscopic improvement (Figure 1B). Eighty-two W52 OZA/OZA responders entered the OLE (moderate, n=45; severe, n=37); efficacy rates at OLE W46 were similar in moderate and severe pts and were maintained through OLE W94 in the observed case analysis (Figure 1C). Overall, the data followed similar patterns in the nonresponder imputation analyses across endpoints. Conclusion: OZA was efficacious and durable in AT-naive UC pts whose disease was inadequately controlled on CTs. Pts with moderate disease benefitted more from OZA during the first year of therapy, especially during induction, but long-term durability of OZA for up to 3 years was similar in moderate and severe OZA clinical responders. OZA may be an appropriate oral AT option for achieving and sustaining long-term benefit in AT-naive UC pts.Figure 1.: Efficacy during TN IP, TN MP, and TN OLE in AT-naive pts by baseline endoscopic disease activity. Table 1. - Demographic and clinical characteristics at baseline in the IP of AT-naive pts by baseline endoscopic disease activity AT-naive moderatea AT-naive severeb PBO (C1) n=64 OZA (C1) n=138 OZA (C2) n=94 PBO (C1) n=73 OZA (C1) n=149 OZA (C2) n=98 Age, y, mean (SD) 42.6 (13.6) 41.9 (13.2) 42.9 (14.9) 42.7 (14.1) 41.8 (13.4) 45.1 (12.8) Males, n (%) 38 (59.4) 78 (56.5) 54 (57.4) 52 (71.2) 86 (57.7) 64 (65.3) Years since UC diagnosis, mean (SD) 6.3 (7.0) 5.5 (5.9) 6.0 (7.4) 5.9 (7.4) 5.9 (6.0) 8.0 (8.5) Extensive disease, n (%) 16 (25.0) 41 (29.7) 21 (22.3) 31 (42.5) 52 (34.9) 32 (32.7) CS use at screening, n (%) 18 (28.1) 23 (16.7) 20 (21.3) 21 (28.8) 40 (26.8) 24 (24.5) Prior 5-ASA use, n (%) 62 (96.9) 135 (97.8) 94 (100.0) 72 (98.6) 146 (98.0) 98 (100.0) Prior CS use, n (%) 42 (65.6) 92 (66.7) 57 (60.6) 47 (64.4) 96 (64.4) 66 (67.3) Prior IMM use, n (%) 15 (23.4) 27 (19.6) 12 (12.8) 18 (24.7) 50 (33.6) 22 (22.4) aModerate pts had MES=2 at baseline.bSevere pts had MES=3 at baseline.5-ASA, 5-aminosalicylate; CS, corticosteroid; IMM, immunomodulator.
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Purpose: Inflammatory bowel disease (IBD) patients may not receive preventive care at the same rate as the general population. Attitudes of primary care providers may be a key factor. Methods: We conducted an anonymous, cross-sectional survey of family medicine practitioners. The survey consisted of 9 demographic items, 2 items to assess comfort level with IBD patients and 6 vignettes of preventive care issues. Mulitple choice answers were designated to represent a range of attitudes toward primary care in IBD patients: 1) active response to perform appropriate preventive health action; 2) minimal involvement; 3) generic lack of involvement and 4) complete lack of involvement based on concept of severe disease state. Results: 42 of 97 surveys were returned. 7/924 responses were left blank (0.75%). Degrees of subjects were as follows: MD 83%, physician assistant 12%, doctor of osteopathy 2% and international medical graduate 2%. Mean year of graduation was 1986. Mean age of subjects was 48. Women comprised 31% of the group. 90% of subjects practice family medicine. 88% of subjects practice mainly in outpatient settings. 16% indicated they were not comfortable with primary care for any patients currently using medical therapy for IBD. But 40% of subjects felt comfortable providing primary care across a range of illness severity, which compares with 48% who reported moderate/high exposure to IBD patients. Vignettes 1 and 6 concerned reaction to mild hypertension. 90% of subjects’ answers represented an attitude of active involvement. Vignette 2 elicited attitudes to lipid measurement in IBD patients. 63% endorsed active response. Vignette 3 assessed attitudes toward cardiovascular risk reduction. 87% endorsed an active role. Vignette 4 addressed need for vaccines in a young patient on maintenance infliximab. Only 26% answered that they would take an active role to vaccinate this person. Vignette 5 also involved vaccines but the age of the patient was 65. 70% of subjects chose the active role. No subject endorsed complete lack of involvement based on a concept of severe disease state. Conclusion: Our study suggests family medicine doctors are uncomfortable caring for IBD patients. Unfamiliarity with medications may be key and explain low endorsement of vaccines for a case patient on infliximab.
Abstract This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504.
Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD.This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response.The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR.Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.
INTRODUCTION: Adequate immunity against preventable infectious diseases is essential for patients with Inflammatory Bowel Disease (IBD) to decrease the risk of infection, morbidity and mortality. However, vaccination rates among patients with IBD appear to be suboptimal. Data from a population-based study showed that only 48.4% of patients with IBD receive a yearly influenza vaccine. Concern about vaccine safety among health care providers and patients plays an important role contibuting to low immunization rates. Hence, in order to reinforce immunization recommendations and to increase compliance, we conducted a systematic review and meta-analysis of observational and clinical trial studies that investigated the vaccination safety for IBD patients. METHODS: We searched PubMed and Embase through April 15th 2020 for studies evaluating the safety of vaccinations among patients with IBD. Studies were included in our analysis if they reported the number of patients with IBD who experienced adverse events (AE) or a change in their IBD activity after vaccination. The primary outcome of interest was the incidence of AE and IBD flares among vaccinated patients. We utilized a random effects meta-analysis of proportions using the DerSimonian-Laird approach to estimate the safety of immunizations among IBD patients. RESULTS: Among 2438 non-duplicate studies, 19 studies with a total of 2483 patients fulfilled our inclusion criteria. The most commonly reported adverse events were minor/local, and they included pain, erythema or swelling at injection site. The pooled incidence of those local/minor AE was 27% (95% CI: 0.11–0.48%). We then analyzed the incidence of systemic AE after the receipt of any vaccine. The most commonly reported systemic adverse events were fevers, myalgia, fatigue and headache and the pooled incidence was 13% (95% CI: 4–26%). Importantly, the pooled incidence of IBD flares associated with the receipt of any vaccine was 1% (95% CI: 0–2%). Finally, 16/19 studies reported no additional serious AE requiring hospitalization other than IBD flares, while in the remaining 3 studies the reported serious AE were likely unrelated to vaccination receipt. No deaths were reported. CONCLUSION: Immunizations for patients with IBD are safe comparable to finding in the general population with a low incidence of local and systemic adverse reactions and flares of IBD. These findings support gastrointestinal society guidelines that clinicians should recommend vaccinations without reservation for patients with IBD.Figure 1.: Study selection flowchart.Figure 2.: Systemic adverse events after immunization.Figure 3.: Inflammatory bowel disease flare after immunization.
