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Crohn's Disease of the Elderly: Unique Biology and Therapeutic Efficacy and Safety

Hong, Simon J; Galati, Jonathan; Katz, Seymour
The incidence and prevalence of inflammatory bowel disease (IBD) is increasing in the elderly population. Compared with patients with onset during younger years, patients with elderly-onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas aging-related biological changes, such as immunosenescence and dysbiosis, are associated with elderly-onset IBD. Frailty is an increasingly recognized predictor of adverse outcomes. As an increasingly wider array of biologic and small molecule therapeutic options becomes available, data regarding efficacy and safety of these agents in patients are paramount given the unique characteristics of this population.
PMID: 35595423
ISSN: 1558-1942
CID: 5235742

Methotrexate and TNF inhibitors affect long-term immunogenicity to COVID-19 vaccination in patients with immune-mediated inflammatory disease

Haberman, Rebecca H; Um, Seungha; Axelrad, Jordan E; Blank, Rebecca B; Uddin, Zakwan; Catron, Sydney; Neimann, Andrea L; Mulligan, Mark J; Herat, Ramin Sedaghat; Hong, Simon J; Chang, Shannon; Myrtaj, Arnold; Ghiasian, Ghoncheh; Izmirly, Peter M; Saxena, Amit; Solomon, Gary; Azar, Natalie; Samuels, Jonathan; Golden, Brian D; Rackoff, Paula; Adhikari, Samrachana; Hudesman, David P; Scher, Jose U
PMCID:8975261
PMID: 35403000
ISSN: 2665-9913
CID: 5218902

COVID-19 is not associated with worse long-term inflammatory bowel disease outcomes: a multicenter case-control study

Hong, Simon J; Bhattacharya, Sumona; Aboubakr, Aiya; Nadkarni, Devika; Lech, Diana; Ungaro, Ryan C; Agrawal, Manasi; Hirten, Robert P; Greywoode, Ruby; Mone, Anjali; Chang, Shannon; Hudesman, David P; Ullman, Thomas; Sultan, Keith; Lukin, Dana J; Colombel, Jean-Frederic; Axelrad, Jordan E
Background/UNASSIGNED:Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. Objectives/UNASSIGNED:We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. Design/UNASSIGNED:We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Methods/UNASSIGNED:Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. Results/UNASSIGNED: = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). Conclusion/UNASSIGNED:In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.
PMCID:9637830
PMID: 36348637
ISSN: 1756-283x
CID: 5357292

Frailty, Thy Diagnosis Is Uncertain: Impact on IBD Readmission and Mortality [Editorial]

Hong, Simon J; Katz, Seymour
PMID: 33748912
ISSN: 1573-2568
CID: 4875382

Implementation of an Inpatient IBD Service Is Associated with Improvement in Quality of Care and Long-Term Outcomes

Hong, Simon J; Jang, Janice; Berg, Dana; Kirat, Tarik; Remzi, Feza; Chang, Shannon; Malter, Lisa B; Axelrad, Jordan E; Hudesman, David P
BACKGROUND:There is wide variation in the quality of care of hospitalized patients with inflammatory bowel disease (IBD). Prior studies have demonstrated that a specialized inpatient IBD service improves short-term outcomes. In this study, we assessed the impact of a dedicated IBD service on the quality of care and long-term outcomes. METHODS:This retrospective cohort study included adult patients admitted for a complication of IBD between March 2017 and February 2019 to a tertiary referral center. In March 2018, a dedicated inpatient IBD service co-managed by IBD gastroenterologists and colorectal surgeons was implemented. Quality of care outcomes included C. difficile stool testing, confirmed VTE prophylaxis administration and opiate avoidance. Long-term outcomes were clinical remission, IBD-related surgery, ED visits, and hospital readmissions at 90 days and 12 months. RESULTS:In total, 143 patients were included; 66 pre- and 77 post-implementation of the IBD service. Fifty-two percent had ulcerative colitis and 48% had Crohn's disease. After implementation, there was improvement in C.difficile testing (90% vs. 76%, P = 0.04), early VTE prophylaxis (92% vs. 77%, P = 0.01) and decreases in narcotic use (14% vs. 30%, P = 0.02), IBD-related ED visits at 90 days (7% vs 18%, P = 0.03) and 12 months (16% vs 30%, P = 0.04), and IBD readmissions at 90 days (16% vs. 30%, P = 0.04). There were no differences in rates of clinical remission or surgery. CONCLUSIONS:The creation of a dedicated inpatient IBD service improved quality of IBD care and reduced post-discharge ED visits and readmissions and broader implementation of this strategy may help optimize care of hospitalized IBD patients.
PMID: 33474649
ISSN: 1573-2568
CID: 4760702

Defining the disease characteristics of concurrent inflammatory bowel disease and psoriasis or psoriatic arthritis [Meeting Abstract]

Rabbenou, W; Jaros, B; Chang, S; Axelrad, J; Scher, J; Hudesman, D; Haberman, R; Hong, S J
Introduction: Inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases characterized by dysregulation of the immune system. Evidence suggests that they share a common genetic and pathophysiologic pathway and that the presence of one increases the risk of developing others. While rates of PsO and PsA are increased in patients with IBD, data is lacking regarding whether phenotypic differences exist in patients with concurrent disease. In this study, we describe the disease characteristics of patients with IBD and PsO/PsA overlap.
Method(s): We performed a single-center case-control observational study. Eighty-five patients with IBD and PsO and/or PsA were identified and matched with a control group of patients with IBD alone in a 1:2 fashion based on age, sex and IBD type (n=190). Patient demographics, IBD phenotype and history, treatment patterns, and family history were collected.
Result(s): We identified 85 patients with IBD and PsO +/-PsA, matched with 190 controls. IBD 1 PsO/PsA patients were less frequently White (85% vs. 94%) and more frequently Asian (7% vs. 3%), compared with IBD only patients (P, 0.01, Table 1). There were no differences in extent of ulcerative colitis (UC) or distribution of Crohn's disease (CD), but patients with IBD alone were more likely to have penetrating Crohn's disease (48% vs. 7%; P, 0.01), prior hospitalizations (48% vs. 28%; P, 0.01), and prior surgeries (35% vs. 17%; P=0.02), compared to patients with overlap PsO +/-PsA. Rates of exposure to various biologic therapies were similar between the two groups, with the exception of decreased vedolizumab use in the IBD 1 PsO/PsA group (12% vs. 31% respectively; P, 0.01, Table 2). IBD only patients were more likely to have first-degree relatives (FDR) with IBD (35% vs. 23%; P=0.02) and numerically less likely to have a FDR with PsO or PsA (14% vs. 20%; P=0.21) than patients with PsO/PsA overlap (Table 1).
Conclusion(s): In this study, we report for the first time disease characteristics of patients with IBD and overlap PsO or PsA. Our results suggests that patients with IBD and PsO/PsA may have a less severe disease phenotype than patients with IBD alone, and that genetic risks may differ between these two groups. Further prospective studies are needed to confirm these findings
EMBASE:636476207
ISSN: 1572-0241
CID: 5083712

Comparative safety of biologic agents in patients with inflammatory bowel disease with active or recent malignancy: A multi-center cohort study [Meeting Abstract]

Holmer, A K; Luo, J; Park, S; Yang, J Y; Nguyen, V Q; Sofia, M A; Ertem, F; Dueker, J M; Petrov, J C; Al, Bawardy B F; Llano, E M; Fudman, D; Joseph, D; Jangi, S; Russ, K; Khakoo, N S; Damas, O; Barnes, E L; Hong, S J; Zenger, C; Axelrad, J; Scott, F I; Ungaro, R; Singh, S
Introduction: With an aging population, management of biologic therapy in IBD patients with active or recent cancer is challenging. We evaluated the comparative safety of non-tumor necrosis factor (TNF)-a directed therapy vs. TNFa antagonists vs. immunomodulator monotherapy (IMM) in IBD patients with active or recent cancer (<=5 years).
Method(s): Through the collaborative REACH-IBD (Rising Educators Academics and Clinicians Helping IBD) research initiative, we conducted a retrospective, multi-center cohort study. We included IBD patients from 12 centers with active cancer (Cohort A) or recent cancer within = years (Cohort B) who were treated with non-TNFa biologics vs. TNFa antagonists (reference) after cancer diagnosis.We excluded patients with nonmelanoma skin cancer. Primary outcomes were cancer progression (Cohort A) or new/recurrent cancer (Cohort B). We performed Cox proportional hazard analysis to compare the safety of different biologics.
Result(s): (Cohort A)We included 107 patients with active cancer (5416y, 62% male, 72% solid cancer, 400 person-year follow-up), of whom 35 were treated with non-TNFa biologics (29 vedolizumab, 6 ustekinumab), 45 with TNFa antagonists and 27 with IMM (Table 1). Overall, 19 patients had progression of cancer, 13 died and 20 were hospitalized for serious infection (Figure 1A). After adjusting for age and type of active cancer, there was no difference in the risk of cancer progression (non-TNFa biologics vs. TNFa antagonists: HR, 1.55; 95% CI, 0.48-5.03), mortality (HR, 2.74; 95% CI, 0.25-30.5) and serious infections (HR, 1.90; 95% CI, 0.15-24.0) between patients treated with non-TNFa biologics vs. TNFa antagonists. (Cohort B) We included 141 patients with recent prior cancer (5214y, 51% male, 86% solid cancer; duration of remission prior to starting biologics, 1719m) of whom 54 were treated with non-TNFa biologics (40 vedolizumab, 14 ustekinumab), 63 with TNFa antagonists and 24 with IMM (Table 1). Overall, 14 patients had recurrence of cancer (or developed new incident cancer) and 6 died (Figure 1B). After adjusting for age, type of prior cancer and duration of remission, there was no difference in the risk of cancer recurrence between non-TNFa biologics vs. TNFa antagonists (HR, 0.97; 95% CI, 0.16-5.75).
Conclusion(s): In IBD patients with active or recent cancer (within = years), non-TNFa-directed biologics and TNFa antagonists have comparable safety. Choice of biologic should be dictated by IBD disease severity, in collaboration with an oncologist
EMBASE:636475073
ISSN: 1572-0241
CID: 5083932

Risk of new or recurrent cancer after vedolizumab or ustekinumab exposure in patients with inflammatory bowel disease and previous cancer [Meeting Abstract]

Zenger, C; Hong, S J; Pecoriello, J; Pang, A S; Vallely, M; Hudesman, D; Chang, S; Axelrad, J
Introduction: Previous studies have demonstrated that exposure to anti-TNFa medications or immunomodulators (IMM) does not increase the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a previous history of cancer. There is little data regarding this risk after the use of newer biologics such as ustekinumab and vedolizumab. In this study, we assessed whether patients with IBD and a history of previous cancer who are exposed to these newer agents have an increased risk of developing subsequent cancer.
Method(s): We performed a retrospective cohort study of patients with IBD and cancer from a single academic medical center between January 2013 and December 2020. We recorded information on demographics, cancer type and treatment, and IBD characteristics and drug exposures. The primary exposure was type of IBD monotherapy after a cancer diagnosis. The primary outcome was development of new or recurrent cancer.
Result(s): Of 401 patients with IBD and a history of cancer, 37 subsequently received vedolizumab, 14 ustekinumab, 31 IMM, 41 anti-TNF, 11 combination anti-TNF with an IMM, and 267 were not exposed to any immunosuppression following a cancer diagnosis (Table 1). There were no differences in duration of IBD, median age at cancer diagnosis, or smoking history. During a total median follow-up of 52 months, 81 (20%) patients developed incident cancer including 6 (16%) exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to IMM, 12 (29%) to anti-TNF, 2 (18%) to combination anti-TNF with an IMM, and 56 (21%) with no immunosuppression (P = 0.41). Sensitivity analyses assessing any history of exposure to vedolizumab or ustekinumab, inclusive of both single and multiple biologic exposures, also did not reveal an increased rate of incident cancer.
Conclusion(s): In this single-center study, vedolizumab or ustekinumab monotherapy in patients with IBD and a history of cancer was not associated with an increase in new or recurrent cancer compared with anti-TNF, IMM, or no immunosuppression. Prospective studies are needed to confirm this conclusion
EMBASE:636474994
ISSN: 1572-0241
CID: 5083972

Ustekinumab Does Not Increase Risk of Adverse Events: A Meta-Analysis of Randomized Controlled Trials

Rolston, Vineet S; Kimmel, Jessica; Popov, Violeta; Bosworth, Brian P; Hudesman, David; Malter, Lisa B; Hong, Simon; Chang, Shannon
GOALS AND BACKGROUND/OBJECTIVE:Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications. STUDY/METHODS:A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18 years or older with a diagnosis of an autoimmune condition. RESULTS:Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16 weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen. CONCLUSIONS:UST was not associated with an increase in short-term risk of AEs.
PMID: 32445049
ISSN: 1573-2568
CID: 4447192

From the American Epicenter: Coronavirus Disease 2019 in Patients with Inflammatory Bowel Disease in the New York City Metropolitan Area

Axelrad, Jordan E; Malter, Lisa; Hong, Simon; Chang, Shannon; Bosworth, Brian; Hudesman, David
BACKGROUND:We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). METHODS:We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. RESULTS:We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn's disease or older men with comorbidities, and 1 patient expired. DISCUSSION/CONCLUSIONS:In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.
PMID: 32578843
ISSN: 1536-4844
CID: 4493232