BACKGROUND & AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class. CONCLUSIONS: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.
Spirochete colonization of the gastrointestinal tract is a poorly understood phenomenon presenting with varying signs and symptoms. Due to the lack of a unified approach and its varying presentations, the management decision for intestinal spirochetosis (IS) has always been challenging. While metronidazole is the commonly preferred antimicrobial treatment, it remains unclear if therapeutic intervention is indicated for everyone, especially asymptomatic patients. We present three patients, diagnosed with IS. They presented with varying demographics, clinical presentations, and past medical histories and underwent different clinical managements. Our decisions for treatment not only included presenting symptoms but also factors like history of pre-existing gastrointestinal diseases, age, and immune status.
Background: The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. Objectives: We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. Design: We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. Methods: Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. Results: From 1 March 2020 to 31 August 2021, there were 2508 patients with IBD who had at least one telehealth appointment, with 1088 (43%) having Crohn's disease (CD), 1037 (41%) having ulcerative colitis (UC), and 383 (15%) having indeterminate colitis. Of the initial telehealth visits, 519 (21%) were not completed, including 435 (20%) among patients <60 years as compared to 84 (23%) among patients ⩾60 years (p = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. Conclusion: Patients with CD, females, and those with less social support were at higher risk for missed telehealth appointments, as were adults >80 years. Engaging older adults via telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.
As the prevalence of older adults with inflammatory bowel disease (IBD) is rising, understanding the unique challenges in both diagnosis and management is becoming increasingly important. Knowledge of phenotypic differences as well as overlapping symptoms with other medical conditions is critical to obtaining a timely diagnosis of IBD in older adults. Although older adults with IBD are at higher risk for adverse events compared with younger adults with IBD, recent data have suggested that ongoing disease activity may be a significant driver of adverse clinical outcomes rather than use of current treatment modalities. Ultimately, earlier and effective treatments can improve outcomes and quality of life for older adults with IBD. However, to help improve medical decision-making, clinicians must move away from the use of chronological age alone and begin to integrate measures of biological age, such as frailty and sarcopenia, into risk stratification tools. This article reviews the management considerations for older adults with IBD and provides the rationale for incorporating measures of biological age into current practice.
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.
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Aged , Biology , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Humans , Incidence , Inflammatory Bowel Diseases/therapy
The management and understanding of Crohn's disease (CD) continues to evolve quickly. Intestinal strictures were previously thought to be an inevitable result of irreversible fibrosis caused by chronic inflammation. However, increased understanding of the dynamic nature of strictures and of the pathophysiology of this condition has highlighted emerging targets for potential treatment. In the diagnosis of strictures, a distinction must be made between inflammatory and fibrotic types, as the former may respond to medical therapy. Emerging technologies, such as dual-energy computed tomography enterography and iodine density, have allowed more accurate characterization of strictures. Surgical and endoscopic treatment remains the mainstay for fibrotic strictures, but developments in systemic and intralesional biologic therapy have shown efficacy. This article reviews the pathophysiology of this debilitating complication of CD as well as current and emerging diagnostics and treatments.
The incidence and prevalence of inflammatory bowel disease (IBD) is rising in the elderly population. Compared with patients with onset during their 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 biological changes associated with aging including immunosenescence, dysbiosis, and frailty have a greater impact on disease outcomes. With the advent of an increasingly wider array of biologic and small-molecule therapeutic options, data regarding efficacy and safety of these agents in elderly IBD patients specifically are paramount, given the unique characteristics of this population.
Inflammatory bowel disease (IBD) is often treated with biologics and immunomodulators, which can place elderly IBD patients at risk for serious and opportunistic infections. This article provides an updated account of research on therapies in IBD that are associated with an increased infection risk. Relevant serious and opportunistic infections in the elderly population are discussed along with methods for prevention and treatment. The incidence of infection increases with age and the degree of immunosuppression. Emphasis should be placed on performing vaccinations at the time of IBD diagnosis. Additionally, patients receiving immunosuppressive therapy should avoid live vaccines. Physicians should have a greater awareness of the increased risk of infection in elderly adults and the need for screening for infection prior to initiation of immunosuppressive IBD therapies.
Small bowel adenocarcinoma is a rare but well-known complication of Crohn's disease. The diagnosis of small bowel adenocarcinoma remains difficult since its presentation is highly variable and mimics active or obstructive Crohn's disease. The diagnosis is often delayed and typically detected only at surgery in an advanced stage with a poor prognosis. We report a case of metastatic ileal adenocarcinoma in a patient with Crohn's disease with prolonged survival. Our case describes serial promising treatment options of these advanced malignancies and raises a possible role for checkpoint immunotherapy.
The role of vitamin D has long been discussed in many chronic diseases, and its significance in inflammatory bowel disease has recently gained attention. This article reviews vitamin D homeostasis, the involvement of vitamin D in the pathophysiology of inflammatory bowel disease, and vitamin D deficiency as a result of inflammatory bowel disease. In addition, this article explores the possibility of age, specifically in the elderly population, as a risk factor for developing vitamin D deficiency in patients with inflammatory bowel disease.
PURPOSE OF REVIEW: Early- and late-onset of inflammatory bowel disease (IBD) may perhaps be etiologically distinct and potentially attributed to genetics, environmental or microbial factors. We review disease factors and clinical characteristics, as well as unique management and treatment strategies to consider when caring for the "baby" or "baby boomer" with IBD. RECENT FINDINGS: Around 25% of cases of initial diagnosis of IBD is made before the age of 18 years old, and another 15-20% made after the age of 60. Crohn's disease (CD) typically presents as ileocolonic and stricturing or penetrating phenotype among early-onset, whereas among late-onset, it is mainly colonic and inflammatory. Pediatric ulcerative colitis (UC) is mostly pan-colonic versus primarily left-sided among the elderly. Treatment goal for both age groups is primarily symptom control, with growth and development also considered among pediatric patients. Due to alterations in pharmacokinetics, careful monitoring and reduced dose should be considered. A multidisciplinary care team is necessary to ensure better clinical outcomes. Onset of disease at either spectrum of age requires careful management and treatment, with both unique disease- and age-appropriate factors carefully considered.
Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10-8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.
Crohn Disease/enzymology , Crohn Disease/genetics , Genetic Predisposition to Disease , Genetic Variation , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Parkinson Disease/enzymology , Parkinson Disease/genetics , Alleles , Autophagy , Cytoskeleton/metabolism , Exome/genetics , Gene Frequency , Gene Regulatory Networks , Genetic Loci , Genome, Human , Humans , Macrophages/metabolism , Macrophages/pathology , Odds Ratio , Open Reading Frames/genetics , Phenotype , Reproducibility of Results , Risk Factors , Exome Sequencing
OPINION STATEMENT: Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is becoming more prevalent with the elderly being the fastest growing group. Parallel to this, there is an increasing interest in the use of complementary and alternative medicine (CAM). Nearly half of patients with IBD have used CAM at one time. The elderly patients, however, are burdened by comorbid conditions, polypharmacy, and altered functional status. With increasing use of complementary and alternative medicine in our elderly patients with IBD, it is vital for the provider to provide counsel on drug-herb potential interactions. CAM includes herbal products, diet, dietary supplements, acupuncture, and prayer. In this paper, we will review common CAM, specifically herbs, that are used in patients with IBD including the herb background, suggested use, evidence in IBD, and most importantly, potential interactions with IBD medications used in elderly patients. Most important evidence-based adverse events and drug-herb interactions are summarized. The herbs discussed include Triticum aestivum (wheat grass), Andrographis paniculata (chiretta), Boswellia serrata, tormentil, bilberry, curcumin (turmeric), Plantago ovata (blond psyllium), Oenothera biennis (evening primrose oil), germinated barley foodstuff, an herbal preparation of myrrh, chamomile and coffee extract, chios mastic gum, wormwood (absinthe, thujone), Cannabis sativa (marijuana, THC), tripterygium wilfordii (thunder god vine), Ulmus rubra (slippery elm bark), trigonella foenugraecum (fenugreek), Dioscorea mexicana (wild yam), Harpagophytum procumbens (devil's claw), ginger, cinnamon, licorice, and peppermint.
The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines.
BACKGROUND: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS: We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS: The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS: Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).
Crohn Disease/drug therapy , Ustekinumab/therapeutic use , Adult , Female , Humans , Induction Chemotherapy , Infusions, Intravenous , Maintenance Chemotherapy , Male , Middle Aged , Remission Induction , Ustekinumab/adverse effects , Ustekinumab/immunology , Ustekinumab/pharmacokinetics
OPINION STATEMENT: As new and effective novel therapies in inflammatory bowel disease (IBD) become available, patients are living longer with advancing age and are at increased risk for malignancy. The management of IBD and malignancy involves multiple combinations of chemotherapy agents and IBD drugs, with the potential for interactions between these therapies. Interactions may either potentiate the effectiveness of drug class or exacerbate their common side effects. In this review article, we present a guide on studied interactions between IBD therapies and chemotherapy agents, specifically those of colorectal cancer, breast cancer, non-Hodgkin's lymphoma, and melanoma. The pharmacology and pharmocokinetics of each IBD drug will be discussed. Then, the IBD drug and chemotherapy interactions are summarized in table format. This guide will provide a quick reference to guide clinicians with this challenging management of two disease processes.
