Searched for: in-biosketch:true
person:katzs04
Drug-Herb Interactions in the Elderly Patient with IBD: a Growing Concern
Rahman, Haider; Kim, Marina; Leung, Galen; Green, Jesse A; Katz, Seymour
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.
PMID: 28918484
ISSN: 1092-8472
CID: 2708792
INFLIXIMAB RE-INTRODUCTION AFTER TEMPORARY DISCONTINUATION: A MULTICENTRIC SURVEY [Meeting Abstract]
Leung, Galen; Faleck, David; Colombel, Jean Frederic; Dubinsky, Marla; Berkowitz, Joshua; Keith, Sultan; Axelrad, Jordan; Cohen, Margot E.; Lawlor, Garrett; Agrawal, Manasi; Lukin, Dana J.; Katz, Seymour; Chen, Lea A.
ISI:000403140301458
ISSN: 0016-5085
CID: 3182892
Interactions Between Inflammatory Bowel Disease Drugs and Chemotherapy
Leung, Galen; Papademetriou, Marianna; Chang, Shannon; Arena, Francis; Katz, Seymour
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.
PMID: 27709332
ISSN: 1092-8472
CID: 2274212
Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease
Feagan, Brian G; Sandborn, William J; Gasink, Christopher; Jacobstein, Douglas; Lang, Yinghua; Friedman, Joshua R; Blank, Marion A; Johanns, Jewel; Gao, Long-Long; Miao, Ye; Adedokun, Omoniyi J; Sands, Bruce E; Hanauer, Stephen B; Vermeire, Severine; Targan, Stephan; Ghosh, Subrata; de Villiers, Willem J; Colombel, Jean-Frederic; Tulassay, Zsolt; Seidler, Ursula; Salzberg, Bruce A; Desreumaux, Pierre; Lee, Scott D; Loftus, Edward V Jr; Dieleman, Levinus A; Katz, Seymour; Rutgeerts, Paul
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 .).
PMID: 27959607
ISSN: 1533-4406
CID: 2357792
Therapeutic Use of Cannabis in Inflammatory Bowel Disease
Ahmed, Waseem; Katz, Seymour
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.
PMCID:5193087
PMID: 28035196
ISSN: 1554-7914
CID: 2383752
Acute Perforating Diverticulitis Associated with Active Ulcerative Colitis: Yes, It Does Occur [Meeting Abstract]
Ahmed, Waseem; Katz, Seymour
ISI:000395764603022
ISSN: 1572-0241
CID: 2492592
A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GMCSF
Chuang, Ling-Shiang; Villaverde, Nicole; Hui, Ken Y; Mortha, Arthur; Rahman, Adeeb; Levine, Adam P; Haritunians, Talin; Ng, Sok Meng Evelyn; Zhang, Wei; Hsu, Nai-Yun; Facey, Jody-Ann; Luong, Tramy; Fernandez-Hernandez, Heriberto; Li, Dalin; Rivas, Manuel; Schiff, Elena R; Gusev, Alexander; Schumm, L Phillip; Bowen, Beatrice M; Sharma, Yashoda; Ning, Kaida; Remark, Romain; Gnjatic, Sacha; Legnani, Peter; George, James; Sands, Bruce E; Stempak, Joanne M; Datta, Lisa W; Lipka, Seth; Katz, Seymour; Cheifetz, Adam S; Barzilai, Nir; Pontikos, Nikolas; Abraham, Clara; Dubinsky, Marla J; Targan, Stephan; Taylor, Kent; Rotter, Jerome I; Scherl, Ellen J; Desnick, Robert J; Abreu, Maria T; Zhao, Hongyu; Atzmon, Gil; Pe'er, Itsik; Kugathasan, Subra; Hakonarson, Hakon; McCauley, Jacob L; Lencz, Todd; Darvasi, Ariel; Plagnol, Vincent; Silverberg, Mark S; Muise, Aleixo M; Brant, Steven R; Daly, Mark J; Segal, Anthony W; Duerr, Richard H; Merad, Miriam; McGovern, Dermot P B; Peter, Inga; Cho, Judy H
BACKGROUND & AIMS: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS: We performed exome-sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony stimulating factor 2 receptor beta common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and GMCSF-responsive cells were defined by mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and expression and functions of gene products were compared. RESULTS: In the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P=8.52x10-4); the finding was validated in the replication cohort (combined P=3.42x10-6). Incubation of intestinal lamina propria leukocytes with GMCSF resulted in high levels of phosphorylation of STAT5 and lesser increases in phosphorylation of ERK and AKT. Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 following stimulation with GMCSF, compared to cells transfected with control CSF2RB, indicating a dominant negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to GMCSF and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. CONCLUSIONS: In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to GMCSF, providing an additional mechanism for alterations to the innate immune response in individuals with CD.
PMCID:5037012
PMID: 27377463
ISSN: 1528-0012
CID: 2195792
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