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Current Gastroenterology Reports

Erschienen in:

01.01.2019 | Inflammatory Bowel Disease (S Hanauer, Section Editor)

Managing Risks with Biologics

verfasst von: Benjamin Click, Miguel Regueiro

Erschienen in: Current Gastroenterology Reports | Ausgabe 2/2019

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Abstract

Purpose of Review

With a rapidly evolving complement of advanced targeted therapies in inflammatory bowel disease, additional safety and side effect concerns emerge. It is the purpose of this review to consider various risks with biologic therapies in inflammatory bowel disease and discuss mitigating strategies.

Recent Findings

Two recently approved monoclonal antibodies (vedolizumab and ustekinumab) and a Janus kinase inhibitor small molecule (tofacitnib) have introduced a number of novel safety and risk considerations. We review the clinical trial and real-world safety data to date on these agents as well as review new data and considerations with anti-tumor necrosis factor agents. New vaccines for varicella zoster virus, hepatitis B virus, and high-dose influenza have been studied, and we discuss the clinical importance of these findings. Lastly, we make management recommendations in the event of particular side effects or complications.

Summary

Understanding the risks of new agents in inflammatory bowel disease, potential mitigating strategies, and management considerations is important to achieving and maintaining clinical outcomes in IBD patients.

Cullen G, Baden RP, Cheifetz AS. Varicella zoster virus infection in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2392–403.CrossRef

Long MD, Martin C, Sandler RS, Kappelman MD. Increased risk of pneumonia among patients with inflammatory bowel disease. Am J Gastroenterol. 2013;108(2):240–8.CrossRef

Long MD, Martin C, Sandler RS, Kappelman MD. Increased risk of herpes zoster among 108 604 patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;37(4):420–9.CrossRef

Tinsley A, Navabi S, Williams ED, Liu G, Kong L, Coates MD, et al. Increased risk of influenza and influenza-related complications among 140,480 patients with inflammatory bowel disease [published online ahead of print July 18, 2018]. Inflamm Bowel Dis. https://doi.org/10.1093/ibd/izy243.

Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, 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.CrossRef

Fidder H, Schnitzler F, Ferrante M, Noman M, Katsanos K, Segaert S, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut. 2009;58(4):501–8.CrossRef

Grijalva CG, Chen L, Delzell E, Baddley JW, Beukelman T, Winthrop KL, et al. Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA. 2011;306(21):2331–9.CrossRef

Lichtenstein GR, Rutgeerts P, Sandborn WJ, Sands BE, Diamond RH, Blank M, et al. A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol. 2012;107(7):1051–63.CrossRef

Bergstrom L, Yocum DE, Ampel NM, Villanueva I, Lisse J, Gluck O, et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists. Arthritis Rheum. 2004;50(6):1959–66.CrossRef

10.

Lee JH, Slifman NR, Gershon SK, Edwards ET, Schwieterman WD, Siegel JN, et al. Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arthritis Rheum. 2002;46(10):2565–70.CrossRef

11.

Velayos FS, Sandborn WJ. Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis. 2004;10(5):657–60.CrossRef

12.

Toruner M, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134(4):929–36.CrossRef

13.

Gisbert JP, Chaparro M, Esteve M. Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33(6):619–33.CrossRef

14.

Loras C, Gisbert JP, Minguez M, Merino O, Bujanda L, Saro C, et al. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut. 2010;59(10):1340–6.CrossRef

15.

Marehbian J, Arrighi HM, Hass S, Tian H, Sandborn WJ. Adverse events associated with common therapy regimens for moderate-to-severe Crohn’s disease. Am J Gastroenterol. 2009;104(10):2524–33.CrossRef

16.

Madonia S, Orlando A, Scimeca D, Olivo M, Rossi F, Cottone M. Occult hepatitis B and infliximab-induced HBV reactivation. Inflamm Bowel Dis. 2007;13(4):508–9.CrossRef

17.

Clarke WT, Amin S, Papamichail K, Feuerstein JD, Cheifetz AS. Patients with resolved HBV infection (anti-Hbc+, Hbsag-) on anti-TNF therapy have a low rate of reactivation. Gastroenterology. 2018;154(6):S364.CrossRef

18.

Ko K-LM, Chen L, Seto W-K, Hung I, Leung WK. Natural history of patients with inflammatory bowel disease who are positive for hepatitis B Core antibody (anti-HBC) and requiring immunosuppresive therapy. Gastroenterology. 2018;154(6):S82.CrossRef

19.

Lee K-M, Lee JM, Kim H-S, Ye BD, Park SJ, Im JP, et al. Hepatitis B virus reactivation in hepatitis B virus infected patients with inflammatory bowel disease receiving antitumor necrosis factor alpha therapy. Gastroenterology. 2018;154(6):S365.CrossRef

20.

• Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut. 2017;66(5):839–51. This post-hoc analysis of pooled data from the GEMINI trials focuses on safety signals including infections, malignancies, immunogenicity and other rare complications with vedolizumab. CrossRef

21.

Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946–60.CrossRef

22.

Loftus EV, Augustin M, Bissonnette R, Krueger G, Calabro S, Langholff W, et al. Prevalence of inflammatory bowel disease among patients with psoriasis and incidence of serious infections in this subset: results from the PSOLAR registry. Gastroenterology. 2016;150(4):S805.

23.

Sandborn WJ, Su C, Sands BE, D'Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376(18):1723–36.CrossRef

24.

Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843–7.CrossRef

25.

Ananthakrishnan AN, Cagan A, Cai T, Gainer VS, Shaw SY, Churchill S, et al. Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2015;41(11):1141–8.CrossRef

26.

Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215–9 quiz e16–7.CrossRef

27.

Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology (Baltimore, Md). 2018;67(4):1560–99.CrossRef

28.

Chen YM, Huang WN, Wu YD, Lin CT, Chen YH, Chen DY, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis. 2018;77(5):780–2.CrossRef

29.

Selby L, Kane S, Wilson J, Balla P, Riff B, Bingcang C, et al. Receipt of preventive health services by IBD patients is significantly lower than by primary care patients. Inflamm Bowel Dis. 2008;14(2):253–8.CrossRef

30.

• Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017;112(2):241–58. Published last year, this guideline incorporates excellent reviews of the literature and makes practical recommendations for an assortment of commonly encountered health maintenance issues in IBD including vaccination, bone-health, and mental health. CrossRef

31.

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):309–18.CrossRef

32.

Melmed GY. Immunizations and IBD: whose responsibility is it? If I’m the prescribing doctor, shouldn't it be mine? Inflamm Bowel Dis. 2012;18(1):41–2.CrossRef

33.

Selby L, Hoellein A, Wilson JF. Are primary care providers uncomfortable providing routine preventive care for inflammatory bowel disease patients? Dig Dis Sci. 2011;56(3):819–24.CrossRef

34.

Wasan SK, Coukos JA, Farraye FA. Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists knowledge. Inflamm Bowel Dis. 2011;17(12):2536–40.CrossRef

35.

Yeung JH, Goodman KJ, Fedorak RN. Inadequate knowledge of immunization guidelines: a missed opportunity for preventing infection in immunocompromised IBD patients. Inflamm Bowel Dis. 2012;18(1):34–40.CrossRef

36.

Wichmann A, Krugliak Cleveland N, Rubin DT. Safety and efficacy of live measles vaccine administered to a Crohn's disease patient receiving vedolizumab. Am J Gastroenterol. 2016;111(4):577.CrossRef

37.

Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–96.CrossRef

38.

Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Diez-Domingo J, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–32.CrossRef

39.

Natori Y, Shiotsuka M, Slomovic J, Hoschler K, Ferreira V, Ashton P, et al. A double blind randomized trial of high dose vs. standard dose influenza vaccine in adult solid organ transplant recipients. Clin Infect Dis. 2018;66(11):1698–1704.

40.

Caldera F, Saha S, Wald A, Grimes I, Hillman L, Zhang Y, et al. Randomized trial evaluating the immunogenicity of high dose vs. standard dose influenza vaccine in IBD patients on anti-tnf monotherapy. Gastroenterology. 2018;154(6):S69.CrossRef

41.

Vermeire S, Noman M, Van Assche G, Baert F, Van Steen K, Esters N, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn's disease: a prospective cohort study. Gastroenterology. 2003;125(1):32–9.CrossRef

42.

Collamer AN, Guerrero KT, Henning JS, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Arthritis Rheum. 2008;59(7):996–1001.CrossRef

43.

Luthra P, Peyrin-Biroulet L, Ford AC. Systematic review and meta-analysis: opportunistic infections and malignancies during treatment with anti-integrin antibodies in inflammatory bowel disease. Aliment Pharmacol Ther. 2015;41(12):1227–36.CrossRef

44.

Kotlyar DS, Osterman MT, Diamond RH, Porter D, Blonski WC, Wasik M, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9(1):36–41.e1.CrossRef

45.

• Lemaitre M, Kirchgesner J, Rudnichi A, Carrat F, Zureik M, Carbonnel F, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017;318(17):1679–86. Perhaps the most definitive IBD and lymphoma trial to date, this is a well-designed and executed study investigating the question of lymphoma risk in IBD patients and risk according to therapies using a French population based dataset. CrossRef

46.

Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA, Pollono EN, Cueto JP, Gonzales-Crespo MR, et al. Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA. 2012;308(9):898–908.CrossRef

47.

Williams CJ, Peyrin-Biroulet L, Ford AC. Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-alpha therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39(5):447–58.CrossRef

48.

Fiorentino D, Ho V, Lebwohl MG, Leite L, Hopkins L, Galindo C, et al. Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry. J Am Acad Dermatol. 2017;77(5):845–54.e5.CrossRef

49.

Gordon KB, Papp KA, Langley RG, Ho V, Kimball AB, Guzzo C, et al. Long-term safety experience of ustekinumab in patients with moderate to severe psoriasis (part II of II): results from analyses of infections and malignancy from pooled phase II and III clinical trials. J Am Acad Dermatol. 2012;66(5):742–51.CrossRef

50.

Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, 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.PubMed

51.

Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017;76(7):1253–62.CrossRef

52.

Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75(5):831–41.CrossRef

53.

Xeljanz (tofacitinib) [package insert]. New York: Pfizer Laboratories; 2018 (update).

54.

Shelton E, Laharie D, Scott FI, Mamtani R, Lewis JD, Colombel JF, 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.CrossRef

55.

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):390–9.e1.CrossRef

56.

Kopylov U, Vutcovici M, Kezouh A, Seidman E, Bitton A, Afif W. Risk of lymphoma, colorectal and skin cancer in patients with IBD treated with immunomodulators and biologics: a Quebec claims database study. Inflamm Bowel Dis. 2015;21(8):1847–53.CrossRef

57.

Ko JM, Gottlieb AB, Kerbleski JF. Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat. 2009;20(2):100–8.CrossRef

58.

Cullen G, Kroshinsky D, Cheifetz AS, Korzenik JR. Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature. Aliment Pharmacol Ther. 2011;34(11–12):1318–27.CrossRef

59.

Guerin M, Haettich B, Bara C, Artru L, Prophette B, Celerier P, et al. Lupus attributable to anti-TNF therapy and revealed by interstitial granulomatous dermatitis. Rheumatol Int. 2012;32(9):2937–40.CrossRef

60.

Mocci G, Marzo M, Papa A, Armuzzi A, Guidi L. Dermatological adverse reactions during anti-TNF treatments: focus on inflammatory bowel disease. J Crohns Colitis. 2013;7(10):769–79.CrossRef

61.

Guarneri C, Lentini M, Polimeni G, Giuffrida R, Cannavo SP. Ustekinumab-induced drug eruption resembling lymphocytic infiltration (of Jessner-Kanof) and lupus erythematosus tumidus. Br J Clin Pharmacol. 2016;81(4):792–4.CrossRef

62.

Seror R, Richez C, Sordet C, Rist S, Gossec L, Direz G, et al. Pattern of demyelination occurring during anti-TNF-alpha therapy: a French national survey. Rheumatology (Oxford, England). 2013;52(5):868–74.CrossRef

63.

Lozeron P, Denier C, Lacroix C, Adams D. Long-term course of demyelinating neuropathies occurring during tumor necrosis factor-alpha-blocker therapy. Arch Neurol. 2009;66(4):490–7.CrossRef

64.

Badat Y, Meissner WG, Laharie D. Demyelination in a patient receiving ustekinumab for refractory Crohn's disease. J Crohns Colitis. 2014;8(9):1138–9.CrossRef

65.

Tillack C, Ehmann LM, Friedrich M, Laubender RP, Papay P, Vogelsang H, et al. Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-gamma-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014;63(4):567–77.CrossRef

66.

Ghabril M, Bonkovsky HL, Kum C, Davern T, Hayashi PH, Kleiner DE, et al. Liver injury from tumor necrosis factor-alpha antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013;11(5):558–64.e3.CrossRef

67.

Rodrigues S, Lopes S, Magro F, Cardoso H, Horta e Vale AM, Marques M, et al. Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: a single center report of 8 cases. World J Gastroenterol. 2015;21(24):7584–8.CrossRef

68.

Shelton E, Chaudrey K, Sauk J, Khalili H, Masia R, Nguyen DD, et al. New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2015;41(10):972–9.CrossRef

69.

Bessissow T, Renard M, Hoffman I, Vermeire S, Rutgeerts P, Van Assche G. Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy. Aliment Pharmacol Ther. 2012;36(4):312–23.CrossRef

70.

Hastings R, Ding T, Butt S, Gadsby K, Zhang W, Moots RJ, et al. Neutropenia in patients receiving anti-tumor necrosis factor therapy. Arthritis Care Res. 2010;62(6):764–9.CrossRef

71.

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710.CrossRef

72.

Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8):711–21.CrossRef

73.

Charles-Schoeman C, Gonzalez-Gay MA, Kaplan I, Boy M, Geier J, Luo Z, et al. Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum. 2016;46(1):71–80.CrossRef

74.

Charles-Schoeman C, Fleischmann R, Davignon J, Schwartz H, Turner SM, Beysen C, et al. Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib. Arthritis Rheumatol (Hoboken, NJ). 2015;67(3):616–25.CrossRef

Titel: Managing Risks with Biologics
verfasst von: Benjamin Click
Miguel Regueiro
Publikationsdatum: 01.01.2019
Verlag: Springer US
Erschienen in: Current Gastroenterology Reports / Ausgabe 2/2019
Print ISSN: 1522-8037
Elektronische ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-019-0669-6

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