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Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies

. 2019 ; 8 () : . [epub] 20190830

Language English Country Great Britain, England Media electronic-ecollection

Document type Journal Article, Research Support, Non-U.S. Gov't, Review

Advances in the treatment of rheumatoid arthritis (RA) are attributed to several aspects such as new classification criteria enabling early diagnosis and intensive treatment with the application of treat-to-target principles as well as better understanding of the pathogenesis of RA contributing to the development of targeted therapies. However, reaching remission is still not achieved in most patients with RA, which is one of the driving forces behind the continuous development of novel therapies and the optimization of therapeutic strategies. This review will outline several new therapeutic antibodies modulating anti-inflammatory cytokines interleukin (IL)-2 and IL-10 and pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor, fractalkine, and IL-6 that are in various stages of clinical development as well as the progress in manufacturing biotechnologies contributing to the next generation of antibodies and their potential to expand the therapeutic armamentarium for RA. In addition, the fate of unsuccessful therapies including agents targeting IL-15, the IL-20 family, IL-21, chemokine CXCL10, B-cell activating factor (BAFF), and regulatory T (Treg) cells or a novel concept targeting synovial fibroblasts via cadherin-11 will be discussed.

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Cho JH, Feldman M: Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nat Med. 2015;21(7):730–8. 10.1038/nm.3897 PubMed DOI PMC

Hench PS, Kendall EC, Slocumb CH, et al. : The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: compound E) and of pituitary adrenocortical hormone in arthritis: preliminary report. Ann Rheum Dis. 1949;8(2):97–104. 10.1136/ard.8.2.97 PubMed DOI PMC

Weinblatt ME, Maier AL: Longterm experience with low dose weekly methotrexate in rheumatoid arthritis. J Rheumatol Suppl. 1990;22:33–8. PubMed

Aletaha D, Neogi T, Silman AJ, et al. : 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580–8. 10.1136/ard.2010.138461 PubMed DOI

Felson DT, Smolen JS, Wells G, et al. : American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70(3):404–13. 10.1136/ard.2011.149765 PubMed DOI

Smolen JS, Breedveld FC, Burmester GR, et al. : Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2015;75(1):3–15. 10.1136/annrheumdis-2015-207524 PubMed DOI PMC

Lipsky PE, van der Heijde DM, St Clair EW, et al. : Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000;343(22):1594–602. 10.1056/NEJM200011303432202 PubMed DOI

Senolt L, Vencovský J, Pavelka K, et al. : Prospective new biological therapies for rheumatoid arthritis. Autoimmun Rev. 2009;9(2):102–7. 10.1016/j.autrev.2009.03.010 PubMed DOI

Buch MH, Emery P: New therapies in the management of rheumatoid arthritis. Curr Opin Rheumatol. 2011;23(3):245–51. 10.1097/BOR.0b013e3283454124 PubMed DOI

Burmester GR, Feist E, Dörner T: Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol. 2014;10(2):77–88. 10.1038/nrrheum.2013.168 PubMed DOI

Stavre Z, Upchurch K, Kay J, et al. : Differential Effects of Inflammation on Bone and Response to Biologics in Rheumatoid Arthritis and Spondyloarthritis. Curr Rheumatol Rep. 2016;18(12):72. 10.1007/s11926-016-0620-x PubMed DOI

Schwartz DM, Kanno Y, Villarino A, et al. : JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843–62. 10.1038/nrd.2017.201 PubMed DOI

Kievit W, Fransen J, de Waal Malefijt MC, et al. : Treatment changes and improved outcomes in RA: an overview of a large inception cohort from 1989 to 2009. Rheumatology (Oxford). 2013;52(8):1500–8. 10.1093/rheumatology/ket166 PubMed DOI

Aletaha D, Smolen JS: Achieving Clinical Remission for Patients With Rheumatoid Arthritis. JAMA. 2019;321(5):457–458. 10.1001/jama.2018.21249 PubMed DOI

Veale DJ, Orr C, Fearon U: Cellular and molecular perspectives in rheumatoid arthritis. Semin Immunopathol. 2017;39(4):343–54. 10.1007/s00281-017-0633-1 PubMed DOI

Azhar A, Ahmad E, Zia Q, et al. : Recent Updates on Molecular Genetic Engineering Approaches and Applications of Human Therapeutic Proteins. Curr Protein Pept Sci. 2017;18(3):217–32. 10.2174/1389203717666160901114911 PubMed DOI

Burgess AW, Metcalf D: The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980;56(6):947–58. PubMed

Zhou D, Huang C, Lin Z, et al. : Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal. 2014;26(2):192–7. 10.1016/j.cellsig.2013.11.004 PubMed DOI

Cook AD, Hamilton JA: Investigational therapies targeting the granulocyte macrophage colony-stimulating factor receptor-α in rheumatoid arthritis: focus on mavrilimumab. Ther Adv Musculoskelet Dis. 2018;10(2):29–38. 10.1177/1759720X17752036 PubMed DOI PMC

Burmester GR, Weinblatt ME, McInnes IB, et al. : Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013;72(9):1445–52. 10.1136/annrheumdis-2012-202450 PubMed DOI PMC

Burmester GR, McInnes IB, Kremer J, et al. : A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2017;76(6):1020–30. 10.1136/annrheumdis-2016-210624 PubMed DOI

Weinblatt ME, McInnes IB, Kremer JM, et al. : A Randomized Phase IIb Study of Mavrilimumab and Golimumab in Rheumatoid Arthritis. Arthritis Rheumatol. 2018;70(1):49–59. 10.1002/art.40323 PubMed DOI PMC

Burmester GR, McInnes IB, Kremer JM, et al. : Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor α Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2018;70(5):679–89. 10.1002/art.40420 PubMed DOI PMC

Buckley C, Simon Campos JA, Yakushin S, et al. : A Phase IIb Dose-ranging Study of Anti-GM-CSF with Methotrexate Treatment in Patients with Rheumatoid Arthritis (RA) and an Inadequate Response to Methotrexate (abstract). Arthritis Rheumatol. 2018;70(suppl 10): abstract number 1938. Reference Source

Huizinga TW, Batalov A, Stoilov R, et al. : Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis. Arthritis Res Ther. 2017;19(1):53. 10.1186/s13075-017-1267-3 PubMed DOI PMC

Papp KA, Gooderham M, Jenkins R, et al. : Granulocyte-macrophage colony-stimulating factor (GM-CSF) as a therapeutic target in psoriasis: randomized, controlled investigation using namilumab, a specific human anti-GM-CSF monoclonal antibody. Br J Dermatol. 2019;180(6):1352–60. 10.1111/bjd.17195 PubMed DOI PMC

Schett G, Bainbridge C, Berkowitz M, et al. : A Phase IIb Study of Anti-GM-CSF Antibody GSK3196165 in Subjects with INflammatory Hand Osteoarthritis (abstract). Arthritis Rheumatol. 2018;70(suppl 10): abstract number 1365. Reference Source

Rafque A, Martin J, Blome M, et al. : Evaluation of the binding kinetics and functional bioassay activity of sarilumab and tocilizumab to the human IL-6 receptor (IL-6R) alpha. Ann Rheum Dis. 2013;72 (suppl 3), abstract number 797. 10.1136/annrheumdis-2013-eular.2360 DOI

Avci AB, Feist E, Burmester GR: Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What's the Difference? BioDrugs. 2018;32(6):531–46. 10.1007/s40259-018-0320-3 PubMed DOI

Weinblatt ME, Mease P, Mysler E, et al. : The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol. 2015;67(10):2591–600. 10.1002/art.39249 PubMed DOI

Genovese MC, Fleischmann R, Furst D, et al. : Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014;73(9):1607–15. 10.1136/annrheumdis-2013-204760 PubMed DOI PMC

Bartoli F, Bae S, Cometi L, et al. : Sirukumab for the treatment of rheumatoid arthritis: update on sirukumab, 2018. Expert Rev Clin Immunol. 2018;14(7):539–47. 10.1080/1744666X.2018.1487291 PubMed DOI

Aletaha D, Bingham CO, 3rd, Tanaka Y, et al. : Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017;389(10075):1206–17. 10.1016/S0140-6736(17)30401-4 PubMed DOI

Takeuchi T, Thorne C, Karpouzas G, et al. : Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017;76(12):2001–8. 10.1136/annrheumdis-2017-211328 PubMed DOI PMC

Taylor PC, Schiff MH, Wang Q, et al. : Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study. Ann Rheum Dis. 2018;77(5):658–66. 10.1136/annrheumdis-2017-212496 PubMed DOI

Klatzmann D, Abbas AK: The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015;15(5):283–94. 10.1038/nri3823 PubMed DOI

Rosenzwajg M, Lorenzon R, Cacoub P, et al. : Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019;78(2):209–17. 10.1136/annrheumdis-2018-214229 PubMed DOI

Tchao N, Gorski KS, Yuraszeck T, et al. : Amg 592 Is an Investigational IL-2 Mutein That Induces Highly Selective Expansion of Regulatory T Cells. Blood. 2017;130(Suppl 1):696 Reference Source PubMed

Saxena A, Khosraviani S, Noel S, et al. : Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine. 2015;74(1):27–34. 10.1016/j.cyto.2014.10.031 PubMed DOI PMC

Galeazzi M, Bazzichi L, Sebastiani GD, et al. : A phase IB clinical trial with Dekavil (F8-IL10), an immunoregulatory 'armed antibody' for the treatment of rheumatoid arthritis, used in combination wiIh methotrexate. Isr Med Assoc J. 2014;16(10):666. PubMed

Verma R, Balakrishnan L, Sharma K, et al. : A network map of Interleukin-10 signaling pathway. J Cell Commun Signal. 2016;10(1):61–7. 10.1007/s12079-015-0302-x PubMed DOI PMC

Maini RNPH, Breedveld PC: Hu lL-10 in subjects with active rheumatoid arthritis (I&A): phase I and cytokine response study. Arthritis Rheum; Abstract Supplement of National Scientific Meeting; Washington,1997;224.

Galeazzi M, Sebastiani G, Voll R, et al. : Dekavil (F8IL10) – update on the results of clinical trials investigating the immunocytokine in patients with rheumatoid arthritis. Ann Rheum Dis 2018;77(2):603–604. 10.1136/annrheumdis-2018-eular.5550 DOI

Nanki T, Imai T, Kawai S: Fractalkine/CX3CL1 in rheumatoid arthritis. Mod Rheumatol. 2017;27(3):392–7. 10.1080/14397595.2016.1213481 PubMed DOI

Tanaka Y, Takeuchi T, Yamanaka H, et al. : OP0223 EFFICACY AND SAFETY OF E6011, AN ANTI-FRACTALKINE MONOCLONAL ANTIBODY, IN MTX-IR PATIENTS WITH RHEUMATOID ARTHRITIS. Ann Rheum Dis. 2019;78(Suppl 2):188 10.1136/annrheumdis-2019-eular.1671 DOI

Ridgley LA, Anderson AE, Pratt AG: What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207–14. 10.1097/BOR.0000000000000470 PubMed DOI PMC

Cavalli G, Dinarello CA: Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford). 2015;54(12):2134–44. 10.1093/rheumatology/kev269 PubMed DOI PMC

Baslund B, Tvede N, Danneskiold-Samsoe B, et al. : Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum. 2005;52(9):2686–92. 10.1002/art.21249 PubMed DOI

Bridgewood C, Watad A, Cuthbert RJ, et al. : Spondyloarthritis: new insights into clinical aspects, translational immunology and therapeutics. Curr Opin Rheumatol. 2018;30(5):526–32. PubMed

Baker KF, Isaacs JD: Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175–87. 10.1136/annrheumdis-2017-211555 PubMed DOI

Kragstrup TW, Andersen T, Heftdal LD, et al. : The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis. Front Immunol. 2018;9:2226. 10.3389/fimmu.2018.02226 PubMed DOI PMC

Šenolt L, Leszczynski P, Dokoupilová E, et al. : Efficacy and Safety of Anti-Interleukin-20 Monoclonal Antibody in Patients With Rheumatoid Arthritis: A Randomized Phase IIa Trial. Arthritis Rheumatol. 2015;67(6):1438–48. 10.1002/art.39083 PubMed DOI

Yellin M, Paliienko I, Balanescu A, et al. : A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(6):1730–9. 10.1002/art.34330 PubMed DOI

Du FH, Mills EA, Mao-Draayer Y: Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment. Auto Immun Highlights. 2017;8(1):12. 10.1007/s13317-017-0100-y PubMed DOI PMC

Damjanov N, Tlustochowicz M, Aelion J, et al. : Safety and Efficacy of SBI-087, a Subcutaneous Agent for B Cell Depletion, in Patients with Active Rheumatoid Arthritis: Results from a Phase II Randomized, Double-blind, Placebo-controlled Study. J Rheumatol. 2016;43(12):2094–100. 10.3899/jrheum.160146 PubMed DOI

Genovese MC, Fleischmann RM, Greenwald M, et al. : Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors. Ann Rheum Dis. 2013;72(9):1461–8. 10.1136/annrheumdis-2012-202775 PubMed DOI

Hepburn TW, Totoritis MC, Davis CB: Antibody-mediated stripping of CD4 from lymphocyte cell surface in patients with rheumatoid arthritis. Rheumatology (Oxford). 2003;42(1):54–61. 10.1093/rheumatology/keg030 PubMed DOI

van Vollenhoven RF, Keystone EC, Strand V, et al. : Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial. Ann Rheum Dis. 2018;77(4):495–9. 10.1136/annrheumdis-2017-212478 PubMed DOI

Finch R, Sostelly A, Sue-Ling K, et al. : OP0224 RESULTS OF A PHASE 2 STUDY OF RG6125, AN ANTI-CADHERIN-11 MONOCLONAL ANTIBODY, IN RHEUMATOID ARTHRITIS PATIENTS WITH AN INADEQUATE RESPONSE TO ANTI-TNFALPHA THERAPY. Ann Rheum Dis. 2019;78(Suppl 2):189 10.1136/annrheumdis-2019-eular.3028 DOI

Schmid AS, Neri D: Advances in antibody engineering for rheumatic diseases. Nat Rev Rheumatol. 2019;15(4):197–207. 10.1038/s41584-019-0188-8 PubMed DOI

Steeland S, Vandenbroucke RE, Libert C: Nanobodies as therapeutics: big opportunities for small antibodies. Drug Discov Today. 2016;21(7):1076–113. 10.1016/j.drudis.2016.04.003 PubMed DOI

Kontermann R: Dual targeting strategies with bispecific antibodies. MAbs. 2012;4(2):182–97. 10.4161/mabs.4.2.19000 PubMed DOI PMC

Neri D: Antibody-Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. Cancer Immunol Res. 2019;7(3):348–54. 10.1158/2326-6066.CIR-18-0622 PubMed DOI PMC

Fleischmann R, De Bruyn S, Duby C, et al. : A Novel Individualized Treatment Approach in Open-Label Extension Study of Ozoralizumab (ATN-103) in Subjects with Rheumatoid Arthritis On a Background of Methotrexate. Arthritis Rheumatol. ACR meeting, abstract number 1311.2012. Reference Source

Holz JB, Sargentini-Maier L, de Bruyn S, et al. : OP0043 Twenty-Four Weeks of Treatment with a Novel Anti-IL-6 Receptor Nanobody® (ALX-0061) Resulted in 84% ACR20 Improvement and 58% DAS28 Remission in a Phase I/Ii Study in RA. Ann Rheum Dis. 2014;72(Suppl 3):A64.1–A64. 10.1136/annrheumdis-2013-eular.248 DOI

Dörner T, Weinblatt M, Beneden KV, et al. : FRI0239 Results of a phase 2b study of vobarilizumab, an anti-interleukin-6 receptor nanobody, as monotherapy in patients with moderate to severe rheumatoid arthritis. Ann Rheum Dis. 2017;76(Suppl 2):575 10.1136/annrheumdis-2017-eular.3746 DOI

Fischer JA, Hueber AJ, Wilson S, et al. : Combined inhibition of tumor necrosis factor α and interleukin-17 as a therapeutic opportunity in rheumatoid arthritis: development and characterization of a novel bispecific antibody. Arthritis Rheumatol. 2015;67(1):51–62. 10.1002/art.38896 PubMed DOI

Khatri A, Klünder B, Peloso PM, et al. : Exposure-response analyses demonstrate no evidence of interleukin 17A contribution to efficacy of ABT-122 in rheumatoid or psoriatic arthritis. Rheumatology (Oxford). 2019;58(2):352–60. 10.1093/rheumatology/key312 PubMed DOI

Kloppenburg M, Peterfy C, Haugen IK, et al. : Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis. Ann Rheum Dis. 2019;78(3):413–20. 10.1136/annrheumdis-2018-213336 PubMed DOI PMC

Fleischmann RM, Bliddal H, Blanco FJ, et al. : A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis Rheumatol. 2019;71(7):1056–1069. 10.1002/art.40840 PubMed DOI

Cheung TT, McInnes IB: Future therapeutic targets in rheumatoid arthritis? Semin Immunopathol. 2017;39(4):487–500. 10.1007/s00281-017-0623-3 PubMed DOI PMC

Virtanen A, Haikarainen T, Raivola J, et al. : Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs. 2019;33(1):15–32. 10.1007/s40259-019-00333-w PubMed DOI PMC

Dörner T, Strand V, Cornes P, et al. : The changing landscape of biosimilars in rheumatology. Ann Rheum Dis. 2016;75(6):974–82. 10.1136/annrheumdis-2016-209166 PubMed DOI PMC

Aletaha D, Smolen JS: Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018;320(13):1360–72. 10.1001/jama.2018.13103 PubMed DOI

Koopman FA, Maanen MA, Vervoordeldonk MJ, et al. : Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis. J Intern Med. 2017;282(1):64–75. 10.1111/joim.12626 PubMed DOI

Frank-Bertoncelj M, Klein K, Gay S: Interplay between genetic and epigenetic mechanisms in rheumatoid arthritis. Epigenomics. 2017;9(4):493–504. 10.2217/epi-2016-0142 PubMed DOI

Filková M, Jüngel A, Gay RE, et al. : MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012;26(3):131–41. 10.2165/11631480-000000000-00000 PubMed DOI

van Vollenhoven RF, Nagy G, Tak PP: Early start and stop of biologics: has the time come? BMC Med. 2014;12: 25. 10.1186/1741-7015-12-25 PubMed DOI PMC

van Steenbergen HW, da Silva JAP, Huizinga TWJ, et al. : Preventing progression from arthralgia to arthritis: targeting the right patients. Nat Rev Rheumatol. 2018;14(1):32–41. 10.1038/nrrheum.2017.185 PubMed DOI PMC

Hilliquin S, Hugues B, Mitrovic S, et al. : Ability of disease-modifying antirheumatic drugs to prevent or delay rheumatoid arthritis onset: a systematic literature review and meta-analysis. Ann Rheum Dis. 2018;77(8):1099–1106. 10.1136/annrheumdis-2017-212612 PubMed DOI

Gerlag DM, Safy M, Maijer KI, et al. : Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2019;78(2):179–85. 10.1136/annrheumdis-2017-212763 PubMed DOI PMC

Pozsgay J, Szekanecz Z, Sármay G: Antigen-specific immunotherapies in rheumatic diseases. Nat Rev Rheumatol. 2017;13(9):525–37. 10.1038/nrrheum.2017.107 PubMed DOI

Pfeifle R, Rothe T, Ipseiz N, et al. : Regulation of autoantibody activity by the IL-23-T H17 axis determines the onset of autoimmune disease. Nat Immunol. 2017;18(1):104–13. 10.1038/ni.3579 PubMed DOI PMC

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