Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Novel Targets For Therapeutic Intervention in Inflammatory Bowel Disease. What is the Best Way to Assess the Safety Profile of a Drug?

Author(s): Clara Yzet, Stacy S. Tse, Maia Kayal, Robert Hirten and Jean-Frédéric Colombel*

Volume 25, Issue 1, 2019

Page: [57 - 63] Pages: 7

DOI: 10.2174/1381612825666190308102021

Price: $65

Abstract

The emergence of biologic therapies has revolutionized the management of inflammatory bowel disease (IBD) by halting disease progression, increasing remission rates and improving long-term clinical outcomes. Despite these well-described benefits, many patients are reluctant to commence therapy due to drug safety concerns. Adverse events can be detected at each stage of drug development and during the post-marketing period. In this article, we review how to best assess the safety parameters of new IBD medications, from the earliest stage of development to population-based registries, with a focus on the special populations often excluded from the evaluation process.

Keywords: Drug development, safety, adverse effect, side effect, biologics, inflammatory bowel disease, clinical trials.

[1]
Selinger CP, Eaden J, Jones DB, et al. Modifiable factors associated with nonadherence to maintenance medication for inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(10): 2199-206.
[2]
Kim SB, Kim KO, Jang BI, et al. Patients’ beliefs and attitudes about their treatment for inflammatory bowel disease in Korea. J Gastroenterol Hepatol 2016; 31(3): 575-80.
[3]
Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: A report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res 2010; 16(6): 1726-36.
[4]
Johnson RA, Rid A, Emanuel E, Wendler D. Risks of phase I research with healthy participants: A systematic review. Clin Trials 2016; 13(2): 149-60.
[5]
Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol 2014; 32(1): 40-51.
[6]
Attarwala H. TGN1412: From Discovery to Disaster. J Young Pharm 2010; 2(3): 332-6.
[7]
Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB. Fundamentals of Clinical Trials 2015.http://link.springer.com/ 10.1007/978-3-319-18539-2 Internet [cited 2018 Aug 3].
[8]
Brody T. Origins of Drugs. Clin Trials 2016; 1-30.http://linkinghub.elsevier.com/retrieve/pii/B9780128042175000011 Internet [cited 2018 Jul 23]
[9]
Brody T. Drug Safety. Clin Trials 2016; 483-568.http://linkinghub.elsevier.com/retrieve/pii/B9780128042175000254 Internet [cited 2018 Aug 3]
[10]
Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: Unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012; 61(12): 1693-700.
[11]
Schreiber S, Feagan B, D’Haens G, et al. Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006; 4(3): 325-34.
[12]
Winthrop KL, Melmed GY, Vermeire S, et al. Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflamm Bowel Dis 2018; 24(10): 2258-65.
[14]
Berlin JA, Glasser SC, Ellenberg SS. Adverse event detection in drug development: recommendations and obligations beyond phase 3. Am J Public Health 2008; 98(8): 1366-71.
[15]
Glasser SP, Salas M, Delzell E. Importance and challenges of studying marketed drugs: What is a phase IV study? Common clinical research designs, registries, and self-reporting systems. J Clin Pharmacol 2007; 47(9): 1074-86.
[16]
Ha C, Ullman TA, Siegel CA, Kornbluth A. Patients enrolled in randomized controlled trials do not represent the inflammatory bowel disease patient population. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 2012; 10(9): 1002-7.
[17]
Nell GKH. Phase IV Studies and Lifecycle Management. Pharmaceutical Medicine and Translational Clinical Research 2018; 383-91.http://linkinghub.elsevier.com/retrieve/pii/B9780128021033000250 Internet [cited 2018 Aug 22].
[18]
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 2006; 4(5): 621-30.
[19]
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol 2012; 107(9): 1409-22.
[20]
Lichtenstein GR, Langholff W, Feagan BG, et al. Mo1800 Risk Factors for Serious Infections in Elderly Patients Receiving Infliximab and Other Crohn’s Disease Therapies: TREATTMRegistry Data. Gastroenterology 2016; 150(4): S779-80.
[21]
D’Haens G, Reinisch W, Colombel J-F, et al. Five-year Safety Data From ENCORE, a European Observational Safety Registry for Adults With Crohn’s Disease Treated With Infliximab [Remicade®] or Conventional Therapy. J Crohn’s Colitis 2017; 11(6): 680-9.
[22]
D’Haens G, Reinisch W, Panaccione R, et al. Lymphoma Risk and Overall Safety Profile of Adalimumab in Patients With Crohn’s Disease With up to 6 Years of Follow-Up in the Pyramid Registry. Am J Gastroenterol 2018; 113(6): 872-82.
[23]
Bourrier A, Carrat F, Colombel J-F, et al. Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Aliment Pharmacol Ther 2016; 43(2): 252-61.
[24]
Lopez A, Mounier M, Bouvier A-M, et al. Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease. Clin Gastroenterol Hepatol 2014; 12(8): 1324-9.
[25]
Sokol H, Beaugerie L, Maynadié M, et al. Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(11): 2063-71.
[26]
Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374(9701): 1617-25.
[27]
Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology 2011; 141(5): 1621-28. e1-5
[28]
Sharrar RG, Dieck GS. Monitoring product safety in the postmarketing environment. Ther Adv Drug Saf 2013; 4(5): 211-9.
[29]
Toki T, Ono S. Spontaneous Reporting on Adverse Events by Consumers in the United States: An Analysis of the Food and Drug Administration Adverse Event Reporting System Database. Drugs Real World Outcomes 2018; 5(2): 117-28.
[30]
Banovac M, Candore G, Slattery J, et al. Patient Reporting in the EU: Analysis of EudraVigilance Data. Drug Saf 2017; 40(7): 629-45.
[31]
Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345(15): 1098-104.
[32]
[33]
Bonovas S, Pantavou K, Evripidou D, et al. Safety of biological therapies in ulcerative colitis: An umbrella review of meta-analyses. Best Pract Res Clin Gastroenterol 2018; 32-33: 43-7.
[34]
Moćko P, Kawalec P, Pilc A. Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis. Pharmacol Rep 2016; 68(6): 1237-43.
[35]
Bonovas S, Lytras T, Nikolopoulos G, Peyrin-Biroulet L, Danese S. Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis. Aliment Pharmacol Ther 2018; 47(4): 454-65.
[36]
Cai T, Parast L, Ryan L. Meta-analysis for rare events. Stat Med 2010; 29(20): 2078-89.
[37]
Hyams JS, Dubinsky MC, Baldassano RN, et al. Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease. Gastroenterology 2017; 152(8): 1901-1914.e3.
[38]
Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet 2011; 157C(3): 175-82.
[39]
McCormack SA, Best BM. Obstetric Pharmacokinetic Dosing Studies are Urgently Needed. Front Pediatr 2014; 2: 9.
[40]
Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernández-Díaz S. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol 2011; 205(1): 51.e1-8.
[41]
Sheffield JS, Siegel D, Mirochnick M, et al. Designing drug trials: considerations for pregnant women. Clin Infect Dis 2014; 59(Suppl. 7): S437-44.
[42]
Coelho J, Beaugerie L, Colombel JF, et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study. Gut 2011; 60(2): 198-203.
[43]
Nørgård B, Pedersen L, Christensen LA, Sørensen HT. Therapeutic drug use in women with Crohn’s disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol 2007; 102(7): 1406-13.
[44]
Kanis SL, de Lima-Karagiannis A, de Boer NKH, van der Woude CJ. Use of thiopurines during conception and pregnancy is not associated with adverse pregnancy outcomes or health of infants at one year in a prospective study. Clin Gastroenterol Hepatol 2017; 15(8): 1232-1241.e1.
[45]
Mahadevan U, Martin CF, Sandler RS, Kane SV, Dubinsky M, Lewis JD. 865 PIANO: A 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology 2012; 142(5): S-149.
[46]
Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development. Gastroenterology 2018; 155(3): 696-704.
[47]
Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012; 143(2): 390-399.e1.
[48]
Shelton E, Laharie D, Scott FI, et al. Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis. Gastroenterology 2016; 151(1): 97-109.e4.
[49]
Stallmach A, Hagel S, Gharbi A, et al. Medical and surgical therapy of inflammatory bowel disease in the elderly - prospects and complications. J Crohn’s Colitis 2011; 5(3): 177-88.
[50]
Sparrow MP, Hande SA, Friedman S, et al. Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine. Aliment Pharmacol Ther 2005; 22(5): 441-6.
[51]
Teml A, Schaeffeler E, Herrlinger KR, Klotz U, Schwab M. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing. Clin Pharmacokinet 2007; 46(3): 187-208.
[52]
Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest 2013; 123(3): 958-65.
[53]
Brassard P, Bitton A, Suissa A, Sinyavskaya L, Patenaude V, Suissa S. Oral corticosteroids and the risk of serious infections in patients with elderly-onset inflammatory bowel diseases. Am J Gastroenterol 2014; 109(11): 1795-802.
[54]
Lobatón T, Ferrante M, Rutgeerts P, Ballet V, Van Assche G, Vermeire S. Efficacy and safety of anti-TNF therapy in elderly patients with inflammatory bowel disease. Aliment Pharmacol Ther 2015; 42(4): 441-51.
[55]
Taleban S, Colombel J-F, Mohler MJ, Fain MJ. Inflammatory bowel disease and the elderly: a review. J Crohn’s Colitis 2015; 9(6): 507-15.
[56]
Papp K, Gottlieb AB, Naldi L, et al. Safety Surveillance for Ustekinumab and Other Psoriasis Treatments From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol 2015; 14(7): 706-14.
[57]
Sandborn WJ, Panes J, D’Haens GR, et al. 904 - Tofacitinib for the Treatment of Ulcerative Colitis: Up to 4.4 Years of Safety Data from Global Clinical Trials. Gastroenterology 2018; 154(6): S-178.
[58]
Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2017; 376(18): 1723-36.
[59]
van de Kerkhof PCM, Griffiths CEM, Reich K, et al. Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol 2016; 75(1): 83-98.e4.
[60]
Hohenberger M, Cardwell LA, Oussedik E, Feldman SR. Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease. J Dermatolog Treat 2018; 29(1): 13-8.
[61]
Côté-Daigneault J, Bouin M, Lahaie R, Colombel J-F, Poitras P. Biologics in inflammatory bowel disease: what are the data? United European Gastroenterol J 2015; 3(5): 419-28.
[62]
Hirten RP, Iacucci M, Shah S, Ghosh S, Colombel J-F. Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders. Clin Gastroenterol Hepatol 2018; 16(9): 1374-84.
[63]
Weinblatt M, Schiff M, Goldman A, et al. Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis 2007; 66(2): 228-34.
[64]
Cargnin S, Genazzani AA, Canonico PL, Terrazzino S. Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis. Pharmacol Res 2018; 135: 102-11.
[65]
Wilson A, Jansen LE, Rose RV, et al. HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2018; 47(5): 615-20.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy