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Management of Inflammatory Bowel Disease in the Elderly
John, Elizabeth S; Katz, Kristina; Saxena, Mark; Chokhavatia, Sita; Katz, Seymour
OPINION STATEMENT: A substantial and growing proportion of patients with inflammatory bowel disease (IBD) are elderly, and these patients require tailored treatment strategies. However, significant challenges exist in the management of this population due to the paucity of data. Establishing the initial diagnosis and assessing the etiology of future symptoms and flares can be challenging as several other prevalent diseases can masquerade as IBD, such as ischemic colitis, diverticular disease, and infectious colitis. Important pharmacologic considerations include reduced glomerular filtration rate and drug-drug interactions in the elderly. No drug therapy is absolutely contraindicated in this population; however, special risk and benefit assessments should be made. Older patients are more susceptible to side effects of steroids such as delirium, fractures, and cataracts. Budesonide can be an appropriate alternative for mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) as it has limited systemic absorption. Pill size and quantity, nephrotoxicity, and difficulty of administration of rectal preparations should be considered with 5-aminosalicylic (5-ASA) therapy. Biologics are very effective, but modestly increase the risk of infection in a susceptible group. Based on their mechanisms, integrin receptor antagonists (e.g., vedolizumab) may reduce these risks. Use of antibiotics for anorectal or fistulizing CD or pouchitis in UC increases the risk of Clostridium difficile infection. Pre-existing comorbidities, functional status, and nutrition are important indicators of surgical outcomes. Morbidity and mortality are increased among IBD patients undergoing surgery, often due to postoperative complications or sepsis. Elderly adults with IBD, particularly UC, have very high rates of venous thromboembolism (VTE). Colonoscopy appears safe, but the optimal surveillance interval has not been well defined. Should the octogenarian, nonagenarian, and centurion undergo colonoscopy? The length of surveillance should likely account for the individual's overall life expectancy. Specific health maintenance should emphasize administering non-live vaccines to patients on thiopurines or biologics and regular skin exams for those on thiopurines. Smoking cessation is crucial to overall health and response to medical therapy, even among UC patients. This article will review management of IBD in the elderly.
PMID: 27387455
ISSN: 1092-8472
CID: 2190942
A PH3 RANDOMISED, MULTICENTER, DOUBLE-BLIND, PLACEBO (PBO)-CONTROLLED STUDY OF USTEKINUMAB (UST) MAINTENANCE THERAPY IN MODERATE-SEVERE CROHN'S DISEASE (CD) PTS: RESULTS FROM IM-UNITI [Meeting Abstract]
Sandborn, WJ; Feagan, BG; Gasink, C; Jacobstein, D; Gao, L-L; Johanns, J; Sands, B; Hanauer, S; Targan, S; Ghosh, S; de Villiers, W; Colombel, J-F; Lee, SD; Dieleman, L; Katz, S; Rutgeerts, P; IM-UNITI Study Grp
ISI:000393603400057
ISSN: 1468-3288
CID: 2472092
A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies
Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn; [Katz, Seymour]
One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.
PMCID:4864319
PMID: 27087321
ISSN: 1537-6605
CID: 2195822
Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis
Sandborn, William J; Feagan, Brian G; Wolf, Douglas C; D'Haens, Geert; Vermeire, Severine; Hanauer, Stephen B; Ghosh, Subrata; Smith, Heather; Cravets, Matthew; Frohna, Paul A; Aranda, Richard; Gujrathi, Sheila; Olson, Allan; [Katz, Seymour]
BACKGROUND: Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract. METHODS: We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12, with higher scores indicating more severe disease; subscores range from 0 to 3, with higher scores indicating more severe disease. The primary outcome was clinical remission (Mayo Clinic score =2, with no subscore >1) at 8 weeks. RESULTS: The primary outcome occurred in 16% of the patients who received 1 mg of ozanimod and in 14% of those who received 0.5 mg of ozanimod, as compared with 6% of those who received placebo (P=0.048 and P=0.14, respectively, for the comparison of the two doses of ozanimod with placebo). Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant; therefore, the hierarchical testing plan deemed the analyses of secondary outcomes exploratory. Clinical response (decrease in Mayo Clinic score of >/=3 points and >/=30% and decrease in rectal-bleeding subscore of >/=1 point or a subscore =1) at 8 weeks occurred in 57% of those receiving 1 mg of ozanimod and 54% of those receiving 0.5 mg, as compared with 37% of those receiving placebo. At week 32, the rate of clinical remission was 21% in the group that received 1 mg of ozanimod, 26% in the group that received 0.5 mg of ozanimod, and 6% in the group that received placebo; the rate of clinical response was 51%, 35%, and 20%, respectively. At week 8, absolute lymphocyte counts declined 49% from baseline in the group that received 1 mg of ozanimod and 32% from baseline in the group that received 0.5 mg. The most common adverse events overall were anemia and headache. CONCLUSIONS: In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety. (Funded by Receptos; TOUCHSTONE ClinicalTrials.gov number, NCT01647516.)
PMID: 27144850
ISSN: 1533-4406
CID: 2195832
How Relative Value Units Undervalue the Cognitive Physician Visit: A Focus on Inflammatory Bowel Disease
Katz, Seymour; Melmed, Gil
PMCID:4872854
PMID: 27231455
ISSN: 1554-7914
CID: 2115162
Fulminant Colitis Following Rituximab Therapy
Lipka, Seth; Katz, Seymour; Crawford, James M
PMCID:4865788
PMID: 27330506
ISSN: 1554-7914
CID: 2157992
Risk of New or Recurrent Cancer in Patients with Inflammatory Bowel Disease and Previous Cancer Exposed to Immunosuppressive and Anti-TNF Agents
Axelrad, Jordan; Bernheim, Oren; Colombel, Jean-Frederic; Malerba, Stefano; Ananthakrishnan, Ashwin; Yajnik, Vijay; Hoffman, Gila; Agrawal, Manasi; Lukin, Dana; Desai, Amit; Mceachern, Elisa; Bosworth, Brian; Scherl, Ellen; Reyes, Andre; Zaidi, Hina; Mudireddy, Prashant; DiCaprio, David; Sultan, Keith; Korelitz, Burton; Wang, Erwin; Williams, Renee; Chen, LeaAnn; Katz, Seymour; Itzkowitz, Steven
BACKGROUND AND AIMS: Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. METHODS: We performed a retrospective analysis of data from 333 patients with IBD treated at 7 academic medical centers who developed cancer and subsequently received treatment with anti-tumor necrosis factor (TNF), anti-TNF with an anti-metabolite (thiopurines, methotrexate), anti-metabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared using the Log-Rank test. RESULTS: During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible due to the relatively small sample sizes. There was no difference in time to (p=0.14) or type of (p= 0.61) incident cancer among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF=0.32; 95% confidence interval [CI], 0.09-1.09; HR for anti-TNF with an anti-metabolite=0.64; 95% CI, 0.26-1.59; HR for an anti-metabolite=1.08; 95% CI, 0.54-2.15) or time to subsequent cancer between study arms (p=.22). CONCLUSION: Based on a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an anti-metabolite following cancer was not associated with an increased risk of incident cancer, compared to patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.
PMID: 26247164
ISSN: 1542-7714
CID: 1709242
Chronic appendicitis: uncommon cause of chronic abdominal pain
Kothadia, Jiten P; Katz, Seymour; Ginzburg, Lev
PMCID:4416293
PMID: 25949528
ISSN: 1756-283x
CID: 1565742
Patients With Inflammatory Bowel Disease and a History of Cancer: The Risk of Cancer Following Exposure to Immunosuppression [Meeting Abstract]
Axelrad, Jordan E.; Bernheim, Oren; Colombel, Jean-Frederic; Malerba, Stefano; Ananthakrishnan, Ashwin N.; Yajnik, Vijay; Hoffman, Gila; Agrawal, Manasi; Lukin, Dana J.; Desai, Amit P.; McEachern, Elisa; Bosworth, Brian; Scherl, Ellen J.; Reyes, Andre; Zaidi, Hina; Mudireddy, Prashant R.; DiCaprio, David; Sultan, Keith; Korelitz, Burton I.; Wang, Erwin; Williams, Renee; Chen, Lea Ann; Katz, Seymour; Itzkowitz, Steven H.
ISI:000360115800112
ISSN: 0016-5085
CID: 3177942
Pathogenesis, diagnosis, and management of ulcerative proctitis, chronic radiation proctopathy, and diversion proctitis
Wu, Xian-Rui; Liu, Xiu-Li; Katz, Seymour; Shen, Bo
: Chronic proctitis refers to persistent or relapsing inflammation of the rectum, which results from a wide range of etiologies with various pathogenic mechanisms. The patients may share similar clinical presentations. Ulcerative proctitis, chronic radiation proctitis or proctopathy, and diversion proctitis are the 3 most common forms of chronic proctitis. Although the diagnosis of these disease entities may be straightforward in the most instances based on the clinical history, endoscopic, and histologic features, differential diagnosis may sometimes become problematic, especially when their etiologies and the disease processes overlap. The treatment for the 3 forms of chronic proctitis is different, which may shed some lights on their pathogenetic pathway. This article provides an overview of the latest data on the clinical features, etiologies, diagnosis, and management of ulcerative proctitis, chronic radiation proctopathy, and diversion proctitis.
PMID: 25687266
ISSN: 1078-0998
CID: 1466722