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Clinical Reviews in Allergy & Immunology

Erschienen in:

13.07.2019

Immunologic Adverse Effects of Biologics for the Treatment of Atopy

verfasst von: Vivian Aranez, Julian Ambrus Jr

Erschienen in: Clinical Reviews in Allergy & Immunology | Ausgabe 2/2020

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Abstract

The use of biologic agents as therapies for atopic diseases such as asthma and atopic dermatitis has increased greatly in recent years. The biological agents used to treat atopic diseases are for the most part monoclonal antibodies that suppress the immune response and reduce inflammation by targeting particular cytokines or other molecules involved in Th1, Th2, or Th17 immune reactions. Various side effects and rare complications have been reported from these agents. In this review, we discuss mechanisms of various adverse effects for the biologic agents currently in use or in development for atopic and inflammatory diseases. Monoclonal antibodies targeting the Th1 and Th17 pathways have been associated with significant side effects, partially due to their ability to cause significant impairment in immune responses to pathogens because of the immunologic alterations that they produce. Biologicals targeting Th2-mediated inflammation have had fewer reported side effects, though many are new and emerging drugs whose adverse effects may remain to be fully elucidated with more use. Therefore, continued long-term safety monitoring is required. As with all therapies, the risks associated with side effects of biologics must be balanced against the benefits these drugs offer for treating atopic diseases. One of the most apparent benefits is the steroid-sparing effect of well-chosen biologic therapy used to treat severe atopic disease. In contrast with the quite favorable safety profile of currently available biologics that target the Th2-mediated immune response, chronic systemic corticosteroid use is associated with significant side effects, many of which impact the majority of patients who are placed on long-term steroid therapy.

Pichler WJ et al (2006) Adverse side-effects to biological agents. Allergy 61(8):912–920PubMed

Aubin F, Carbonnel F, Wendling D (2013) The complexity of adverse side-effects to biological agents. J Crohns Colitis 7(4):257–262PubMed

Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJT (2010) The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 9(4):325–338PubMed

Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlén SE, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P (2009) A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 179(7):549–558PubMed

Holgate ST, Noonan M, Chanez P, Busse W, Dupont L, Pavord I, Hakulinen A, Paolozzi L, Wajdula J, Zang C, Nelson H, Raible D (2011) Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J 37(6):1352–1359PubMed

Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285PubMed

Dinarello CA, Simon A, van der Meer JWM (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 11(8):633–652PubMedPubMedCentral

Bottin C, Fel A, Butel N, Domont F, Remond AL, Savey L, Touitou V, Alexandra JF, LeHoang P, Cacoub P, Bodaghi B, Saadoun D (2018) Anakinra in the treatment of patients with refractory scleritis: a pilot study. Ocul Immunol Inflamm 26(6):915–920PubMed

Junge G, Mason J, Feist E (2017) Adult onset Still’s disease-the evidence that anti-interleukin-1 treatment is effective and well-tolerated (a comprehensive literature review). Semin Arthritis Rheum 47(2):295–302PubMed

10.

Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, Muskardin TLW, Reed A, Reynolds JC, Goldbach-Mansky R, Sanchez GAM (2017) Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight 2(16)

11.

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ (2017) Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377(12):1119–1131PubMed

12.

Hugle B et al (2017) Inflammatory bowel disease following anti-interleukin-1-treatment in systemic juvenile idiopathic arthritis. Pediatr Rheumatol Online J 15(1):16PubMedPubMedCentral

13.

Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, Bossuyt X, Boutten A, Bienvenu J, Duquesne A, Richer O, Chaussabel D, Mogenet A, Banchereau J, Treluyer JM, Landais P, Pascual V (2011) A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 70:747–754PubMed

14.

Hart KM, Choy DF, Bradding P, Wynn TA, Arron. Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma. Ann Transl Med, 2017. 5(4):91

15.

Noda S, Suarez-Farinas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H et al (2015) The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol 136(5):1254–1264PubMed

16.

Identifier NCT01478360. Safety, tolerability, and efficacy of AIN457 in patients with uncontrolled asthma. National Library of medicine: ClinicalTrials.gov.

17.

Identifier NCT03568136. Investigation of efficacy of secukinumab in patients with moderate to serve atopic dermatitis. National Library of Medicine: ClinicalTrials.gov.

18.

van de Kerkhof PC et al (2016) 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 75(1):83–98 e4PubMed

19.

Patel NU et al (2017) A review of the use of secukinumab for psoriatic arthritis. Rheumatol Ther 4:233–246PubMedPubMedCentral

20.

Luo, J., et al., Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab. J Mol Biol, 2010. 402(5): p. 797–812

21.

Khattri, S., et al., Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol, 2017. 26(1): p. 28–35

22.

Saeki H, Kabashima K, Tokura Y, Murata Y, Shiraishi A, Tamamura R, Randazzo B, Imanaka K (2017) Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol 177(2):419–427PubMed

23.

Bangsgaard N, Zachariae C, Menné T, Skov L (2011) Lack of effect of ustekinumab in treatment of allergic contact dermatitis. Contact Dermatitis 65(4):227–230PubMed

24.

Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371(9625):1665–1674PubMed

25.

Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371(9625):1675–1684PubMed

26.

Croxtall JD (2011) Ustekinumab: a review of its use in the management of moderate to severe plaque psoriasis. Drugs 71(13):1733–1753PubMed

27.

Johansson SG, Haahtela T, O’Byrne PM (2002) Omalizumab and the immune system: an overview of preclinical and clinical data. Ann Allergy Asthma Immunol 89(2):132–138PubMed

28.

Cox, L., Platts-Mills, T.A., Finegold, I., Schwartz, L.B., Simons, F.E., Wallace, D.V. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol, 2007. 120(6): p. 1373–1377

29.

Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, Gupta N (2001) Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 108(2):184–190PubMed

30.

Iribarren, C., Rahmaoui A., Long A.A., Szefler S.J., Bradley M.S., Carrigan G., Eisner M.D., Chen H., Omachi T.A., Farkouh M.E., Rothman K.J. Cardiovascular and cerebrovascular events among patients receiving omalizumab: results from EXCELS, a prospective cohort study in moderate to severe asthma. J Allergy Clin Immunol, 2017.139: p. 1489–1495

31.

Lefebvre P, Duh MS, Lafeuille MH, Gozalo L, Desai U, Robitaille MN, Albers F, Yancey S, Ortega H, Forshag M, Lin X, Dalal AA (2015) Acute and chronic systemic corticosteroid-related complications in patients with severe asthma. J Allergy Clin Immunol 136:1488–1495PubMed

32.

Omachi TA et al (2014) Asthma severity and increased risk of cardiovascular and cerebrovascular outcomes in patients with moderate-to-severe persistent asthma. Ann Allergy Asthma Immunol (113(suppl, 5):A37

33.

Iribarren C., Rothman K. J., Bradley M. S., Carrigan G., Eisner M. D., Chen H., Cardiovascular and cerebrovascular events among patients receiving omalizumab: pooled analysis of patient-level data from 25 randomized, double-blind, placebo-controlled clinical trials. J Allergy Clin Immunol 2017.139: p. 1678–1680

34.

Milgrom, H., et al., Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma. Curr Med Res pin, 2011. 27(1): p. 163–9

35.

Dreyfus DH, Randolph CC (2006) Characterization of an anaphylactoid reaction to omalizumab. Ann Allergy Asthma Immunol 96(4):624–627PubMed

36.

Pilette C, Coppens N, Houssiau FA, Rodenstein DO (2007) Severe serum sickness–like syndrome after omalizumab therapy for asthma. J Allergy Clin Immunol 120(4):972–973PubMed

37.

Harrison, R.G., et al., Anaphylaxis and serum sickness in patients receiving omalizumab: reviewing the data in light of clinical experience. Ann Allergy Asthma Immunol, 2015. 115(1): p. 77–78

38.

Menzella F et al (2015) Profile of anti-IL-5 mAb mepolizumab in the treatment of severe refractory asthma and hypereosinophilic diseases. J Asthma Allergy 8:105–114PubMedPubMedCentral

39.

Molfino, N.A., et al., Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy, 2012. 42(5): p. 712–37

40.

Roufosse FE, Kahn JE, Gleich GJ, Schwartz LB, Singh AD, Rosenwasser LJ, Denburg JA, Ring J, Rothenberg ME, Sheikh J, Haig AE, Mallett SA, Templeton DN, Ortega HG, Klion AD (2013) Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol 131(2):461–7 e1-5PubMed

41.

GlaxoSmithKline. Nucala (mepolizumab) for injection, for subcutaneous use. 2015. https:www.gsksource.com/pharma

42.

Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O’Brien C, Korn S (2015) Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 3(5):355–366PubMed

43.

Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'Acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ (2010) Medi-563, a humanized anti-IL-5 receptor a mAb with enhanced antibody-dependent cell mediated cytotoxicity function. J Allergy Clin Immunol 125(6):1344–1353PubMed

44.

Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkström V, Goldman M (2016) Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomized, multicentre, placebo-controlled phase 3 trial. Lancet 388(10056):2115–2127PubMed

45.

FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkström V, Aurivillius M, Goldman M (2016) Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 388(10056):2128–2141PubMed

46.

Corren, J., et al., Lebrikizumab treatment in adults with asthma. N Engl J Med, 2011. 365(12): p. 1088–98

47.

Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, Yokoyama A, Olsson J, Gray S, Holweg CTJ, Eisner M, Asare C, Fischer SK, Peng K, Putnam WS, Matthews JG (2016) Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med 4(10):781–796PubMed

48.

Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G (2013) Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 368(26):2455–2466PubMed

49.

Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, Eckert L, Graham NMH, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A (2016) Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomized double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 388(10039):31–44PubMed

50.

Singh D, Ravi A, Southworth T (2017) CRTH2 antagonists in asthma: current perspectives. Clin Pharm 9:165–173

51.

Singh, D., et al., Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459. Eur Respir J, 2013. 41(1): p. 46–52

52.

Barnes, N., et al., A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin Exp Allergy, 2012. 42(1): p. 38–48

53.

Horak, F., et al., The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial. Allergy, 2012. 67(12): p. 1572–9

54.

Bateman ED, O'Brien C, Rugman P, Luke S, Ivanov S, Uddin M (2018) Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β2-agonists in patients with atopic asthma. Drug Des Devel Ther 12:1093–1106PubMedPubMedCentral

55.

Verstraete K, Peelman F, Braun H, Lopez J, van Rompaey D, Dansercoer A, Vandenberghe I, Pauwels K, Tavernier J, Lambrecht BN, Hammad H, de Winter H, Beyaert R, Lippens G, Savvides SN (2017) Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma. Nat Commun 8:14937PubMedPubMedCentral

56.

Park LS, Martin U, Garka K, Gliniak B, di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG, Ziegler SF, Morrissey PJ, Paxton R, Sims JE (2000) Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 192(5):659–670PubMedPubMedCentral

57.

Corren, J., et al., Tezepelumab in adults with uncontrolled asthma. N Engl J Med, 2017. 377(10): p. 936–946

58.

Parker, J.M., et al., Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm Med, 2011. 11: p. 14

59.

Oh CK, Leigh R, McLaurin KK, Kim K, Hultquist M, Molfino NA (2013) A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir Res 14:93PubMedPubMedCentral

60.

National Heart, Lung, and Blood Institute.2002 Morbidity and mortality: 2002. Bethesda (MD): National Heart, Lung, and Blood Institute;

61.

Oba Y, Salzman GA (2004) Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol 114:265–269PubMed

62.

Wu A et al (2007 November) Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model. J Allergy Clin Immunol 120(5):1146–1152PubMedPubMedCentral

63.

Whittington MD, McQueen RB, Ollendorf DA, Tice JA, Chapman RH, Pearson SD, Campbell JD (2017) Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis. Ann Allergy Asthma Immunol 118(2):220–225PubMed

64.

Kuznik A, Bégo-le-Bagousse G, Eckert L, Gadkari A, Simpson E, Graham CN, Miles LS, Mastey V, Mahajan P, Sullivan SD (2017) Economic evaluation of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Dermatol Ther 7:493–505

Titel: Immunologic Adverse Effects of Biologics for the Treatment of Atopy
verfasst von: Vivian Aranez
Julian Ambrus Jr
Publikationsdatum: 13.07.2019
Verlag: Springer US
Erschienen in: Clinical Reviews in Allergy & Immunology / Ausgabe 2/2020
Print ISSN: 1080-0549
Elektronische ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-019-08739-8

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Immunologic Adverse Effects of Biologics for the Treatment of Atopy

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