Secukinumab, a novel anti–IL-17A antibody, shows low immunogenicity potential in human in vitro assays comparable to other marketed biotherapeutics with low clinical immunogenicity

mAbs

Volumn 8, Issue 3, 2016, Pages 536-550

  Karle, Anette ^a   Spindeldreher, Sebastian ^a   Kolbinger, Frank ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

AIN457; Anti drug antibodies; antigen presentation assay; dendritic cell; IL 17A; immunogenicity prediction; major histocompatibility complex associated peptide proteomics; psoriasis; secukinumab; T cell assay

Indexed keywords

ADALIMUMAB; INFLIXIMAB; INTERLEUKIN 17; RITUXIMAB; SECUKINUMAB; EPITOPE; IL17A PROTEIN, HUMAN; MONOCLONAL ANTIBODY;

ARTICLE; BIOLOGICAL THERAPY; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; HUMAN; HUMAN CELL; IMMUNOGENICITY; MAJOR HISTOCOMPATIBILITY COMPLEX; PROTEOMICS; SEQUENCE ANALYSIS; T LYMPHOCYTE ACTIVATION; ANTAGONISTS AND INHIBITORS; CD4+ T LYMPHOCYTE; CYTOLOGY; DENDRITIC CELL; DRUG EFFECTS; FEMALE; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MALE; PRECLINICAL STUDY;

ANTIBODIES, MONOCLONAL; CD4-POSITIVE T-LYMPHOCYTES; DENDRITIC CELLS; DRUG EVALUATION, PRECLINICAL; EPITOPES, T-LYMPHOCYTE; FEMALE; HUMANS; INTERLEUKIN-17; LYMPHOCYTE ACTIVATION; MALE;

EID: 84961205663     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2015.1136761     Document Type: Article

References (75)

1. D.A.Martin, J.E.Towne, G.Kricorian, P.Klekotka, J.E.Gudjonsson, J.G.Krueger, C.B.Russell. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol 2013; 133:17-26; PMID:22673731; http://dx.doi.org/10.1038/jid.2012.194
2. M.A.Lowes, T.Kikuchi, J.Fuentes-Duculan, I.Cardinale, L.C.Zaba, A.S.Haider, E.P.Bowman, J.G.Krueger. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008; 128:1207-11; PMID:18200064; http://dx.doi.org/10.1038/sj.jid.5701213
3. C.Johansen, P.Usher, R.B.Kjellerup, D.Lundsgaard, L.Iverson, K.Kragballe. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 2009; 160:319-24; PMID:19016708; http://dx.doi.org/10.1111/j.1365-2133.2008.08902.x
4. A.M.Lin, C.J.Rubin, R.Khandpur, J.Y.Wang, M.Riblett, S.Yalavarthi, E.C.Villaneuva, P.Shah, M.J.Kaplan, A.T.Bruce. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol 2011; 187:490-500; PMID:21606249; http://dx.doi.org/10.4049/jimmunol.1100123
5. P.C.Res, G.Piskin, O.J.deBoer, C.M.van der Loos, P.Teeling, J.D.Bos, M.B.Teunissen. Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggest their involvement in the pathogenesis of psoriasis. PLoS One 2010; 5:e14108; PMID:21124836; http://dx.doi.org/10.1371/journal.pone.0014108
6. +T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol 2009; 86:435-43; PMID:19487306; http://dx.doi.org/10.1189/JLB.0109046
7. R.G.Langley, B.E.Elewski, M.Lebwohl, K.Reich, C.E.Griffiths, K.Papp, L.Puig, H.Nakagawa, L.Spelman, B.Sigurgeirsson, E.Rivas, et al. ERASURE Study Group; FIXTURE Study Group. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med 2014; 371:326-38; PMID:25007392; http://dx.doi.org/10.1056/NEJMoa1314258
8. A.Blauvelt, J.C.Prinz, A.B.Gottlieb, K.Kingo, H.Sofen, M.Ruer-Mulard, V.Singh, R.Pathan, C.Papavassilis, S.Cooper; FEATURE Study Group. Secukinumab administration by pre-filled syringe: efficacy, safety, and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015; 172:484-93; PMID:25132411; http://dx.doi.org/10.1111/bjd.13348
9. C.Paul, J.P.Lacour, L.Tedremets, K.Kreutzer, S.Jazayeri, S.Adams, C.Guindon, R.You, C.Papavassilis. JUNCTURE Study Group. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015; 29:1082-90; PMID:25243910; http://dx.doi.org/10.1111/jdv.12751
10. U.Mrowietz, C.L.Leonardi, G.Girolomoni, D.Toth, A.Morita, S.A.Balki, J.C.Szepietowski, P.Regnault, H.Thurston, C.Papavassilis, SCULPTURE Study Group. Secukinumab retreatment-as-needed vs. fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE). J Am Acad Dermatol 2015 Jul; 73(1):277–36.e1; http://dx.doi.org/10.1016/j.jaad.2015.04.011. Epub 2015 May 14.
11. D.Thaçi, J.Humeniuk, Y.Frambach, R.Bissonnette, J.J.Goodman, S.Shevade, Y.Gong, C.Papavassilis. STATURE Study Group. Secukinumab in psoriasis: randomized, controlled phase 3 trial results assessing the potential to improve treatment response in partial responders (STATURE). Br J Dermatol 2015 Sep; 173(3):777–87; http://dx.doi.org/10.1111/bjd.13814. Epub 2015 May 16.
12. P.J.Mease, I.B.McInnes, B.Kirkham, A.Kavanaugh, P.Rahman, D.van der Heijde, R.Landewé, P.Nash, L.Pricop, J.Yuan, et al. Secukinumab interleukin-17A inhibition in patients with psoriatic arthritis. N Engl J Med 2015; 373:1329-39; PMID:26422723; http://dx.doi.org/10.1056/NEJMoa1412679
13. I.B.McInnes, P.J.Mease, B.Kirkham, A.Kavanaugh, C.T.Ritchlin, P.Rahman, D.van der Heijde, R.Landewé, P.G.Conaghan, A.B.Gottlieb, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 386:1137-46; PMID:26135703; http://dx.doi.org/10.1016/S0140-6736(15)61134-5
14. D.Baeten, J.Braun, X.Baraliakos, J.Sieper, M.Dougados, P.Emery, A.A.Deodhar, B.Porter, R.Martin, S.Mpofu, et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a 52-week phase 3 randomized placebo-controlled trial with intravenous loading and subcutaneous maintenance dosing. Arthritis Rheumatol 2014; 66:S360.
15. J.Sieper, J.Braun, X.Baraliakos, D.L.Baeten, M.Dougados, P.Emery, A.A.Deodhar, B.Porter, M.Andersson, S.Mpofu, et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a phase 3, randomized, placebo-controlled trial with subcutaneous loading and maintenance dosing. Arthritis Rheumatol 2014; 66:S232; http://dx.doi.org/10.1002/art.38604
16. P.J.Mease, I.McInnes, B.Kirkham, A.Kavanaugh, P.Rahman, D.van der Heijde, R.Landewé, P.Nash, L.Pricop, J.Yuan, et al. Secukinumab, a human anti–interleukin-17A monoclonal antibody, improves active psoriatic arthritis and inhibits radiographic progression: efficacy and safety data from a phase 3 randomized, multicenter, double-blind, placebo-controlled study. Arthritis Rheumatol 2014; 66:S423.
17. L.Xue, T.Hickling, R.Song, J.Nowak, B.Rup. Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody. Clin Exp Immunol. 2016 jan; 183(1):102–13; http://dx.doi.org/10.1111/cei.12711
18. R.T.Purcell, R.F.Lockey. Immunologic responses to therapeutic biologic agents. J Invest Allergol Clin Immunol 2008; 18(5):335-42
19. M.W.Leach, J.B.Rottman, M.B.Hock, D.Finco, J.L.Rojko, J.C.Beyer. Immunogenicity/hypersensitivity of biologics. Toxicol Pathol 2014; 42:293-300; PMID:24240973; http://dx.doi.org/10.1177/0192623313510987
20. J.Descotes. Immunotoxicity of monoclonal antibodies. mAbs 2009; 1:104-10; PMID:20061816; http://dx.doi.org/10.4161/mabs.1.2.7909
21. C.De Simone, P.Amerio, G.Amoruso, F.Bardazzi, A.Campanati, A.Conti, P.Gisondi, G.Gualdi, C.Guarneri, L.Leoni, et al. Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue. Expert Opin Biol Ther 2013; 13:1673-82; PMID:24107126; http://dx.doi.org/10.1517/14712598.2013.848194
22. D.Jullien, J.C.Prinz, F.O.Nestle. Immunogenicity of biotherapy used in psoriasis: the science behind the scenes. J Invest Dermatol 2014; 135:31-8; PMID:25120005; http://dx.doi.org/10.1038/jid.2014.295
23. A.L.Nelson, E.Dhimolea, J.M.Reichert. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 2010; 9:767-74; PMID:20811384; http://dx.doi.org/10.1038/nrd3229
24. A.S.De Groot, D.W.Scott. Immunogenicity of protein therapeutics. Trend Immunol 2007; 28:482-90; http://dx.doi.org/10.1016/j.it.2007.07.011
25. F.A.Harding, M.M.Stickler, J.Razo, R.B.DuBridge. The immunogenicity of humanized and fully human antibodies: residual immunogenicity residue in the CDR regions. mAbs 2010; 2:256-65; PMID:20400861; http://dx.doi.org/10.4161/mabs.2.3.11641
26. P.A.van Schouwenburg, S.Kruithof, C.Votsmeier, K.van Schie, M.H.Hart, R.N.de Jong, E.E.van Buren, M.van Ham, L.Aarden, G.Wolbink, et al. Functional analysis of the anti-adalimumab response using patient-derived monoclonal antibodies. J Biol Chem 2014; 289:34482-8; PMID:25326381; http://dx.doi.org/10.1074/jbc.M114.615500
27. S.Malucchi, A.Bertolotto. Clinical aspects of immunogenicity to biotherapeutics. In: M.van de Weert, E.H.Moller, eds. Immunogenicity of Biopharmaceuticals. New York, NY: Springer Science-Business Media, LLC. 2008.
28. V.Rombach-Riegraf, A.C.Karle, B.Wolf, L.Sorde, S.Koepke, S.Gottlieb, J.Krieg, M.C.Djidja, A.Baban, S.Spindeldreher, et al. Aggregation of human recombinant monoclonal antibodies influences the capacity of dendritic cells to stimulate adaptive T-cell responses in vitro. PLoS One 2014; 9:e86322; PMID:24466023; http://dx.doi.org/10.1371/journal.pone.0086322
29. M.K.Joubert, M.Hokum, C.Eakin, L.Zhou, M.Deshpande, M.P.Baker, T.J.Goletz, B.A.Kerwin, N.Chirmule, L.O.Narhi, V.Jawa. Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses. J Biol Chem 2012; 287:25266-79; PMID:22584577; http://dx.doi.org/10.1074/jbc.M111.330902
30. K.D.Ratanji, J.P.Derrick, R.J.Dearman, I.Kimber. Immunogenicity of therapeutic proteins: influence of aggregation. J Immunotoxicol 2014; 11:99-109; PMID:23919460; http://dx.doi.org/10.3109/1547691X.2013.821564
31. I.Van Walle, Y.Gansemans, P.W.Parren, P.Stas, I.Lasters. Immunogenicity screening in protein drug development. Expert Opin Biol Ther 2007; 7:405-18; PMID:17309332; http://dx.doi.org/10.1517/14712598.7.3.405
32. J.M.Vyas, A.G.Van der Veen, H.L.Ploegh. The known unknowns of antigen processing and presentation. Nat Rev Immunol 2008; 8:607-18; PMID:18641646; http://dx.doi.org/10.1038/nri2368
33. R.M.Chicz, R.G.Urban, W.S.Lane, J.C.Gorga, L.J.Stern, D.A.Vignali, J.L.Strominger. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 1992; 358:764-8; PMID:1380674; http://dx.doi.org/10.1038/358764a0
34. C.A.Weber, P.J.Mehta, M.Ardito, L.Moise, B.Martin, A.S.De Groot. T cell epitope: friend or foe? Immunogenicity of biologics in context. Adv Drug Deliv Rev 2009; 30:965-76; http://dx.doi.org/10.1016/j.addr.2009.07.001
35. V.Jawa, L.P.Cousens, M.Awwad, E.Wakshull, H.Kropshofer, A.S.De Groot. T-cell dependent immunogenicity of protein therapeutics: preclinical assessment and mitigation. Clin Immunol 2013; 149:534-55; PMID:24263283; http://dx.doi.org/10.1016/j.clim.2013.09.006
36. N.K.Mehra. Histocompatibility antigens. Encyclopedia of Life Sciences 2001. Available at: http://web.udl.es/usuaris/e4650869/docencia/GenClin/content/recursos_classe_(pdf)/revisionsPDF/HLA.pdf. Accessed 18June2015.
37. T.Shiina, K.Hosomichi, H.Inoko, J.K.Kulski. The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 2009; 54:15-39; PMID:19158813; http://dx.doi.org/10.1038/jhg.2008.5
38. C.Oseroff, J.Sidney, R.Vita, V.Tripple, D.M.McKinney, S.Southwood, T.M.Brodie, F.Sallusto, H.Grey, R.Alam, et al. T cell responses to known allergen proteins are differently polarized and account for a variable fraction of total response to allergen extracts. J Immunol 2012; 189:1800-11; PMID:22786768; http://dx.doi.org/10.4049/jimmunol.1200850
39. D.M.McKinney, S.Southwood, D.Hinz, C.Oseroff, C.S.Arlehamn, V.Schulten, R.Taplitz, D.Broide, W.A.Hanekom, T.J.Scriba, et al. A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics 2013; 65:357-70; PMID:23392739; http://dx.doi.org/10.1007/s00251-013-0684-y
40. A.S.De Groot, R.Tassone, L.P.Cousens, F.Terry, R.Martin, M.Ardito, W.Martin. In silico prediction of HLA-DP and -DQ epitope content is poorly correlated with clinical immunogenicity of therapeutic proteins, manuscript in preparation, Abstract presented at the American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference (NBC), San Diego, CA, USA. May 20-22, 2013.
41. L.Hsu, B.T.Snodgrass, A.W.Armstrong. Antidrug antibodies in psoriasis: a systematic review. Br J Dermatol 2014; 170:261-73; PMID:24117166; http://dx.doi.org/10.1111/bjd.12654
42. T.Bito, R.Nishikawa, M.Hatakeyama, A.Kikusawa, H.Kanki, H.Nagai, Y.Sarayami, T.Ikeda, H.Yoshizaki, H.Seto, et al. Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis. Br J Dermatol 2014; 170:922-9; PMID:24329764; http://dx.doi.org/10.1111/bjd.12791
43. J.M.Carrascosa. Immunogenicity in biologic therapy: implications for dermatology. Actas Dermosifiliogr 2013; 104:471-9; PMID:23622932; http://dx.doi.org/10.1016/j.ad.2013.02.005
44. M.E.Farhangian, S.R.Feldman. Immunogenicity of biologic treatments for psoriasis: therapeutic consequences and the potential value of concomitant methotrexate. Am J Clin Dermatol 2015 Aug; 16(4):285-94. http://dx.doi.org/ 10.1007/s40257–015–0131–y
45. D.D.Anthony, K.A.Milkovich, W.Zhang, B.Rodriguez, N.L.Yonkers, M.Tary-Lehmann, P.V.Lehmann. Dissecting the T cell response: proliferation assays vs. cytokine signatures by ELISPOT. Cells 2012; 1:127-40; PMID:24710419; http://dx.doi.org/10.3390/cells1020127
46. H.Kropshofer, S.Spindeldreher, T.A.Röhn, N.Platania, C.Grygar, N.Daniel, A.Wölpl, H.Langen, V.Horejsi, A.B.Vogt. Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes. Nat Immunol 2002; 3:61-8; PMID:11743588; http://dx.doi.org/10.1038/ni750
47. T.A.Röhn, A.Reitz, A.Paschen, X.D.Nguyen, D.Schadendorf, A.B.Voight, H.Kropshofer. A novel strategy for the discovery of MHC class II-restricted tumor antigens: identification of a melanotransferrin helper T-cell epitope. Cancer Res 2005; 65:10068-78; PMID:16267033; http://dx.doi.org/10.1158/0008-5472.CAN-05-1973
48. H.Kropshofer, T.Singer. Overview of cell-based tools for pre-clinical assessment of immunogenicity of biotherapeutics. J Immunotoxicol 2006; 3:131-6; PMID:18958693; http://dx.doi.org/10.1080/15476910600845625
49. B.Rup, M.Pallardy, D.Sikkema, T.Albert, M.Allez, P.Broet, C.Carini, P.Creeke, J.Davidson, N.De Vries, et al. ABIRISK Consortium. Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the innovative medicines initiative ABIRISK consortium. Clin Exp Immunol 2015 May 8; 181(3):385-400; http://dx.doi.org/10.1111/cei.12652. [Epub ahead of print].
50. G.Shankar, S.Arkin, L.Cocea, V.Devanarayan, S.Kirshner, A.Kromminga, V.Quarmby, S.Richards, C.K.Schneider, M.Subramanyam, S.Swanson, et al. American Association of Scientists. Assessment and reporting of the clinical immunogenicity of therapeutic proteins and peptides-harmonized terminology and tactical recommendations. AAPS J 2014; 16:658-73; PMID:24764037; http://dx.doi.org/10.1208/s12248-014-9599-2
51. M.G.Tovey, J.Legrand, C.Lallemand. Overcoming immunogenicity associated with the use of biopharmaceuticals. Expert Rev Clin Pharmacol 2011; 4:623-631; PMID:22114889; http://dx.doi.org/10.1586/ecp.11.39
52. K.Bendtzen. Immunogenicity of Anti-TNF-α Biotherapies: I. Individualized medicine based on immunopharmacological evidence. Front Immunol 2015 Apr 8; 6:152; http://dx.doi.org/10.3389/fimmu.2015.00152
53. A.Jaber, M.Baker. Assessment of the immunogenicity of different interferon β-1a formulations using ex vivo T-cell assays. J Pharm Biomed Anal 2007; 43:1256-61; PMID:17118612; http://dx.doi.org/10.1016/j.jpba.2006.10.023
54. M.Sauerborn. The Immunogenicity of Therapeutic Antibodies. Handbook of Therapeutic Antibodies: Wiley-VCH Verlag GmbH & Co. KGaA. 2014; pp. 665-680.
55. D.Wullner, L.Zhou, E.Bramhall, A.Kuck, T.J.Goletz, S.Swanson, N.Chirmule, V.Jawa. Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics. Clin Immunol 2010; 137: 5-14; PMID:20708973; http://dx.doi.org/10.1016/j.clim.2010.06.018
56. A.Kim, S.Sadegh-Nasseri. Determinants of immunodominance for CD4 T cells. Curr Opin Immunol 2015; 34:9-15; PMID:25576665; http://dx.doi.org/10.1016/j.coi.2014.12.005
57. A.C.Karle, G.J.Oostingh, S.Mutschlechner, F.Ferreira, P.Lackner, B.Bohle, G.F.Fischer, A.B.Vogt, A.Duschl. Nitration of the pollen allergen bet v 1.0101 enhances the presentation of bet v 1-derived peptides by HLA-DR on human dendritic cells. PLoS One 2012; 7(2):e31483; PMID:22348091; http://dx.doi.org/10.1371/journal.pone.0031483
58. A.M.Scott, F.T.Lee, R.Jones, W.Hopkins, D.MacGregor, J.S.Cebon, A.Hannah, G.Chong, A.Papenfuss, A.Rigopoulos, et al. A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake. Clin Cancer Res 2005; 11:4810-7; PMID:16000578; http://dx.doi.org/10.1158/1078-0432.CCR-04-2329
59. 124I-huA33 antibody PET of colorectal cancer. J Nucl Med 2011; 52:1173-80; PMID:21764796; http://dx.doi.org/10.2967/jnumed.110.086165
60. Y.T.Ting, S.Temme, N.Koch, A.D.McLellan. A new monoclonal antibody recognizing a linear determinant on the HL-DRα chain N-terminus. Hybridoma 2009; 28:423-9; PMID:20025501; http://dx.doi.org/10.1089/hyb.2009.0050
61. L.Hsu, A.W.Armstrong. Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response. Expert Rev Clin Immunol 2013; 9:949-58; PMID:24128157; http://dx.doi.org/10.1586/1744666X.2013.836060
62. C.L.Krieckaert, G.M.Bartelds, W.F.Lerns, G.J.Wolbink. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review. Arthritis Res Ther 2010; 12:217-22; PMID:21029481; http://dx.doi.org/10.1186/ar3147
63. D.Mazilu, D.Opris, C.Gainaru, M.Iliuta, N.Apetrei, G.Luca, A.Borangiu, T.Gudu, A.Peltea, L.Gorseanu, et al. Monitoring drug and antidrug levels: a rational approach in rheumatoid arthritis patients treated with biologic agents who experience inadequate response while being on a stable biologic treatment. Biomed Res Int 2014:702701; http://dx.doi.org/10.1155/2014/702701
64. M.K.de Vries, G.J.Wolbink, S.O.Stapel, H.de Vrieze, J.C.van Denderen, B.A.Dijkmans, L.A.Aarden, I.E.van der Horst-Bruinsma. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation. Ann Rheum Dis 2007; 66:1252-4; PMID:17472991; http://dx.doi.org/10.1136/ard.2007.072397
65. M.Zisapel, D.Zisman, N.Madar-Balakirski, U.Arad, H.Padova, H.Matz, H.Maman-Sarvagyl, I.Kaufman, D.Paran, J.Feld, et al. Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis. J Rheumatol 2015; 42:73-8; PMID:25399390
66. C.L.Krieckaert, A.Jamnitski, M.T.Nurmohamed, P.J.Kostense, M.Boers, G.Wolbink. Comparison of long-term clinical outcome with etanercept treatment and adalimumab treatment of rheumatoid arthritis with respect to immunogenicity. Arthritis Rheum 2012; 64:3850-5; PMID:22933315; http://dx.doi.org/10.1002/art.34680
67. M.K.de Vries, E.Brouwer, I.E.van der Horst-Bruinsma, A.Spoorenberg, J.C.van Denderen, A.Jamnitski, M.T.Nurmohamed, B.A.Dijkmans, L.A.Aarden, G.J.Wolbink. Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis 2009; 68:1787-8; PMID:19822712; http://dx.doi.org/10.1136/ard.2009.109702
68. J.E.Paramarta, D.L.Baeten. Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral spondyloarthritis: no association with clinical response to treatment or with disease relapse upon treatment discontinuation. Arthritis Res Ther 2014; 16:R160; PMID:25074046; http://dx.doi.org/10.1186/ar4675
69. A.W.van Kujik, M.de Groot, S.O.Stapel, B.A.Dijkmans, G.J.Wolbink, P.P.Tak. Relationship between the clinical response to adalimumab treatment and serum levels of adalimumab and anti-adalimumab antibodies in patients with psoriatic arthritis. Ann Rheum Dis 2010; 69:624-5; PMID:20223840; http://dx.doi.org/10.1136/ard.2009.108787
70. R.F.van Vollenhoven, P.Emery, C.O.Bingham3rd, E.C.Keystone, R.Fleischmann, D.E.Furst, K.Macey, M.Sweetser, A.Kelman, R.Rao. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol 2010; 37:558-67; PMID:20110520; http://dx.doi.org/10.3899/jrheum.090856
71. C.C.Mok. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther 2013; 4:87-100; http://dx.doi.org/10.2147/DDDT.S41645
72. C.Ritchlin, P.Rahman, A.Kavanaugh, I.B.McInnes, L.Puig, S.Li, Y.Wang, Y.K.Shen, D.K.Doyle, A.M.Mendelsohn, et al. PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumor necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis 2014; 73:990-9; PMID:24482301; http://dx.doi.org/10.1136/annrheumdis-2013-204655
73. W.J.Sandborn, C.Gasink, L.L.Gao, M.A.Blank, J.Johanns, C.Guzzo, B.E.Sands, S.B.Hanauer, S.Targan, P.Rutgeerts, et al. CERTIFI Study Group. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med 2012; 367:1519-28; PMID:23075178; http://dx.doi.org/10.1056/NEJMoa1203572
74. N.Emi Aikawa, J.F.de Carvalho, C.Artur Alemida Silva, E.Bonfa. Immunogenicity of anti-TNF-α agents in autoimmune diseases. Clin Rev Allergy Immunol 2010; 38:82-9; PMID:19565360; http://dx.doi.org/10.1007/s12016-009-8140-3
75. M.C.Genovese, P.Durez, H.B.Richards, J.Supronik, E.Dokoupilova, V.Mazurov, J.A.Aelion, S.H.Lee, C.E.Codding, H.Kellner, et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 2013; 72:863-9; PMID:22730366; http://dx.doi.org/10.1136/annrheumdis-2012-201601