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Review

Immunogenicity-unwanted immune responses to biological drugs – can we predict them?

ORCID Icon, , , , &
Pages 47-53 | Received 27 Jan 2020, Accepted 18 May 2020, Published online: 08 Jun 2020

References

  • Vincent FB, Morand EF, Murphy K, et al. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective. Ann Rheum Dis. 2013;72:165–178.
  • Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013;108:40–47.
  • Bartelds G, Krieckaert C. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305:1460–1468.
  • Arstikyte I, Kapleryte G, Butrimiene I, et al. Influence of immunogenicity on the efficacy of long-term treatment with TNF α blockers in rheumatoid arthritis and spondyloarthritis patients. Biomed Res Int. 2015;2015:604872.
  • Hoshino M, Yoshio T, Onishi S, et al. Influence of antibodies against infliximab and etanercept on the treatment effectiveness of these agents in Japanese patients with rheumatoid arthritis. Mod Rheumatol. 2012;22:532–540.
  • Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608.
  • Wolbink GJ, Vis M, Lems W, et al. Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:711–715.
  • De Vries MK, Brouwer E, van der Horst-bruinsma IE, et al. Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis. 2009;68:1787–1788.
  • Moussa EM, Panchal JP, Moorthy BS, et al. Immunogenicity of therapeutic protein aggregates. J Pharm Sci. 2016;105:417–430.
  • Ratanji KD, Derrick JP, Dearman RJ, et al. Immunogenicity of therapeutic proteins: influence of aggregation. J Immunotoxicol. 2014;11:99–109.
  • Gorovits B, Wakshull E, Pillutla R, et al. Recommendations for the characterization of immunogenicity response to multiple domain biotherapeutics. J Immunol Methods. 2014;408:1–12.
  • Hermeling S, Crommelin DJA, Schellekens H, et al. Structure-immunogenicity relationships of therapeutic proteins. Pharm Res. 2004;21:897–903.
  • Vultaggio A, Matucci A, Nencini F, et al. Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy. 2010;65:657–661.
  • Krintel SB, Grunert VP, Hetland M, et al. The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure. Rheumatology. 2013;52:1245–1253.
  • Bender NK, Heilig CE, Dröll B, et al. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int. 2007;27:269–274.
  • Ducourau E, Mulleman D, Paintaud G, et al. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther. 2011;13:R105.
  • Vultaggio A, Petroni G, Pratesi S, et al. Circulating T cells to infliximab are detectable mainly in treated patients developing anti-drug antibodies and hypersensitivity reactions. Clin Exp Immunol. 2016;186(3):364–372.
  • Chiu HY, Chu TW, Cheng YP, et al. The Association between clinical response to ustekinumab and immunogenicity to ustekinumab and prior adalimumab. PLoS One. 2015;10(11):e0142930.
  • Papp KA, Griffiths CE, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168:844–854.
  • Vultaggio A, Matucci A, Nencini F, et al. Drug-specific Th2 cells and IgE antibodies in a patient with anaphylaxis to rituximab. Int Arch Allergy Immunol. 2012;159:321–326.
  • Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. New Engl J Med. 2008;358:1109–1117.
  • Stubenrauch K, Wessels U, Birnboeck H, et al. Subset analysis of patients experiencing clinical events of a potentially immunogenic nature in the pivotal clinical trials of tocilizumab for rheumatoid arthritis: evaluation of an antidrug antibody ELISA using clinical adverse event-driven immunogenicity testing. Clin Ther. 2010;32:1597–1609.
  • Vennegoor A, Rispens T, Strijbis EM, et al. Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis. Mult Scler. 2013;19:593–600.
  • Liefferinckx C, Minsart C, Cremer A, et al. Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance. Eur J Gastroenterol Hepatol. 2019;31(4):478–485.
  • Nencini F, Pratesi S, Petroni G, et al. Assays and strategies for immunogenicity assessment of biological agents. Drug Dev Res. 2014;75(Suppl 1):S4–S6.
  • Bloem K, van Leeuwen A, Verbeek G, et al. Systematic comparison of drug-tolerant assays for anti-drug antibodies in a cohort of adalimumab-treated rheumatoid arthritis patients. J Immunol Methods. 2015;418:29–38.
  • Llinares-Tello F, Rosas-gómez de Salazar J, Senabre-Gallego JM, et al. Practical application of acid dissociation in monitoring patients treated with adalimumab. Rheumatol Int. 2014;34:1701–1708.
  • Lallemand C, Kavrochorianou N, Steenholdt C, et al. Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists. J Immunol Methods. 2011;373:229–239.
  • Bella Ungar B, Chowers Y, Yavzori M, et al. ABIRISK consortium. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut. 2014;63:1258–1264.
  • Hoxha A, Calligaro A, Tonello M, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: a prospective multicentre study. Joint Bone Spine. 2016;83:167–171.
  • Nencini F, Vultaggio A, Pratesi S, et al. The kinetics of antidrug antibodies, drug levels, and clinical outcomes in infliximab-exposed patients with immune-mediated disorders. J Allergy Clin Immunol Pract. 2018;6:2065–2072.e2.
  • Pratesi S, Nencini F, Grosso F, et al. T cell response to infliximab in exposed patients: a longitudinal analysis. Front Immunol. 2019;9:3113.
  • Vultaggio A, Nencini F, Pratesi S, et al. IL-10-producing infliximab-specific T cells regulate the anti-drug T cell response in exposed patients. J Immunol. 2017;199(4):1283–1289.
  • Strand V, Balsa A, Al-Saleh J, et al. Immunogenicity of biologics in chronic inflammatory diseases: a systematic review. BioDrugs. 2017;31(4):299–316.
  • Harding FA, Stickler MM, Razo J, et al. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. mAbs. 2010;2(3):256–265.
  • Radstake TRDJ, Svenson M, Eijsbouts AM, et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheumatic Dis. 2009;68(11):1739–1745.
  • Chen D-Y, Chen Y-M, Hung W-T, et al. Immunogenicity, drug trough levels and therapeutic response in patients with rheumatoid arthritis or ankylosing spondylitis after 24-week golimumab treatment. Ann Rheum Dis. 2015;74(12):2261–2264.
  • Chovel-Sella A, Karplus R, Sella T, et al. Clinical efficacy and adverse effects of golimumab in the treatment of rheumatoid arthritis. Isr Med Assoc J. 2012;14(6):390–394.
  • Zidi I, Bouaziz A, Mnif W, et al. Golimumab therapy of rheumatoid arthritis: an overview. Scand J Immunol. 2010;72(2):75–85.
  • Rath T, Baker K, Dumont JA, et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol. 2015;35(2):235–254.
  • So Yun L, Moon Sung K, Woo Yeup J, et al. Hyaluronic acid-based theranostic nanomedicines for targeted cancer therapy. Cancers (Basel). 2020;12:940–957.
  • Scott LJ. Tocilizumab: a review in rheumatoid arthritis. Drugs. 2017;77(17):1865–1879.
  • Burmester GR, Choy E, Kivitz A, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76(6):1078–1085.
  • Blair HA, Deeks ED. Abatacept: a review in rheumatoid arthritis. Drugs. 2017;77(11):1221–1233.
  • Genovese MC, Pacheco-Tena C, Covarrubias A, et al. Longterm safety and efficacy of subcutaneous abatacept in patients with rheumatoid arthritis: 5-year results from a phase IIIb trial. J Rheumatol. 2018;45(8):1085–1092.
  • Matucci A, Nencini F, Rossi O, et al. The percentage of patients achieving complete remission of urticaria increases with repeated courses of treatment. J Allergy Clin Immunol Pract. 2019;7(1):339–340.
  • Holgate ST, Chuchalin AG, Hebert J, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34(4):632–638.
  • Odajima H, Ebisawa M, Nagakura T, et al. Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma. Allergol Int. 2017;66(1):106–115.
  • Prussin C, Griffith DT, Boesel KM, et al. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol. 2003;112(6):1147–1154.
  • Schroeder JT, Bieneman AP, Chichester KL, et al. Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization. J Allergy Clin Immunol. 2010;125(4):896–901.e6.
  • Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390–400.
  • Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115–2127.
  • Gisbert JP, Marín AC, Chaparro M. The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease: systematic review and meta- analysis. Am J Gastroenterol. 2016;111(5):632–647.
  • Steenholdt C, Al-khalaf M, Brynskov J, et al. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2209–2217.
  • Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology. 2004;126(2):402–413.
  • Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. New Engl J Med. 2007 19; 357(3):239–250. DOI
  • Matucci A, Pratesi S, Petroni G, et al. Allergological in vitro and in vivo evaluation of patients with hypersensitivity reactions to infliximab. Clin Exp Allergy. 2013;43:659–664.
  • Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004;50(5):1400–1411.
  • Ben-Bassat O, Hauenstein S, Iacono A, et al. Serum adalimumab and immunogenicity in IBD patients after 80 mg biweekly maintenance therapy. Gastroenterology. 2013;144(5):S771.
  • Takeuchi T, Yamamoto K, Yamanaka H, et al. THU0190 Better clinical responses seen early with the loading dose of certolizumab pegol are maintained until one year. Ann Rheum Dis. 2014;73:247.
  • Sieper J, Landewe R, Rudwaleit M, et al. Effect of certolizumab pegol over ninety-six weeks in patients with axial spondyloarthritis: results from a phase III randomized trial. Arthritis Rheumatol. 2015;67(3):668–677.
  • Abe T, Takeuchi T, Miyasaka N, et al. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. J Rheumatol. 2006;33(1):37–44.
  • Zhuang Y, Xu Z, Frederick B, et al. Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study. Clin Ther. 2012;34(1):77–90.
  • Amano K, Matsubara T, Tanaka T, et al. Japan Abatacept Study Group.Long-term safety and efficacy of treatment with subcutaneous abatacept in Japanese patients with rheumatoid arthritis who are methotrexate inadequate responders. Mod Rheumatol. 2015;25(5):665–671.
  • Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425–440.
  • Bar-Yoseph H, Pressman S, Blatt A, et al. Infliximab-tumor necrosis factor complexes elicit formation of anti-drug antibodies. Gastroenterology. 2019;157(5):1338–1351.e8.
  • Somerfield J, Hill-Cawthorne GA, Lin A, et al. A novel strategy to reduce the immunogenicity of biological therapies. J Immunol. 2010;185:763–768.
  • Van Schie KA, Kruithof S, Ooijevaar-de Heer P, et al. Restricted immune activation and internalisation of anti-idiotype complexes between drug and antidrug antibodies. Ann Rheum Dis. 2018;77:1471–1479.
  • Krishna M, Nadler SG. Immunogenicity to biotherapeutics - the role of anti-drug immune complexes. Front Immunol. 2016;2(7):21.
  • Jani M, Barton A, Warren RB, et al. The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases. Rheumatology. 2014;53:213–222.
  • Hambardzumyan K, Hermanrud C, Marits P, et al. Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: results from the SWEFOT trial population. Scand J Rheumatol. 2019;48(5):362–366.
  • Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms. Arthritis Rheum. 2009;60(8):2541–2542.
  • Astermark J, Oldenburg J, Pavlova A, et al. Polymorphisms in the IL10 but not in the IL1beta and IL4 genes are associated with inhibitor development in patients with haemophilia A. Blood. 2006 15; 107(8):3167–3172. DOI
  • Jawa V, Cousens LP, Awwad M, et al. T-cell dependent immunogenicity of protein therapeutics: preclinical assessment and mitigation. Clin Immunol. 2013;149:534–555.
  • Schaeverbeke T, Truchetet ME, Kostine M, et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology. 2016;55:210–220.
  • Thomas SS, Borazan N, Barroso N, et al. Comparative Immunogenicity of TNF inhibitors: impact on clinical efficacy and tolerability in the management of autoimmune diseases. a systematic review and meta-analysis. BioDrugs. 2015;29:241–258.
  • Burmester GR, Durez P, Shestakova G, et al. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology. 2016;55(1):49–55.
  • Liu M, Degner J, Davis JW, et al. Identification of HLA-DRB1 association to adalimumab immunogenicity. PLoS One. 2018;13(4):e0195325.
  • Billiet T, Vande Casteele N, Van Stappen T, et al. Immunogenicity to infliximab is associated with HLA-DRB1. Gut. 2015;64(8):1344–1345.
  • Sazonovs A, Kennedy NA, Moutsianas L, et al. HLA-DQA1*05 Carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn’sDisease. Gastroenterology. 2020;158(1):189–199.
  • Louis E, Ghoul Z, Vermeire S, et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn’s disease. Aliment Pharmacol Ther. 2004;19:511–519.
  • Ternant D, Berkane Z, Picon L, et al. Assessment of the influence of inflammation and FCGR3A genotype on infliximab pharmacokinetics and time to relapse in patients with Crohn’s disease. Clin Pharmacokinet. 2015;54:551–562.
  • Romero-Cara P, Torres-Moreno D, Pedregosa J, et al. A FCGR3A polymorphism predicts anti-drug antibodies in chronic inflammatory bowel disease patients treated with anti-TNF. Int J Med Sci. 2018;15(1):10–15.
  • Anderson PJ. Tumor necrosis factor inhibitors: clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum. 2005;34(S1):19–22.
  • Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. Aaps J. 2012;14(2):296–302.
  • Smith KJ, Jones RB, Burns SM, et al. Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse and re-treatment. Arthritis Rheum. 2006;54:2970–2982.
  • Schioppo T, Ingegnoli F. Current perspective on rituximab in rheumatic diseases.. Drug Des Dev Ther. 2017;11:2891–2904.
  • Vermeire S, Gils A, Accossato P, et al. Immunogenicity of biologics in inflammatory bowel diseases. Ther Adv Gastroenterol. 2008;11:1–13.

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