Discriminating phenotypic signatures identified for tocilizumab, adalimumab, and tofacitinib monotherapy and their combinations with methotrexate

Journal of Translational Medicine

Volumn 16, Issue 1, 2018, Pages

  O'Mahony, Alison ^a   John, Markus R ^b   Cho, Hannah ^a   Hashizume, Misato ^b   Choy, Ernest H ^c  

^a Eurofins Medinet Inc   (Germany)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

^c CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Biological therapy; Disease modifying antirheumatic drugs; Inflammation; Ligands; Rheumatoid arthritis

Indexed keywords

ADALIMUMAB; BIOLOGICAL MARKER; METHOTREXATE; TOCILIZUMAB; TOFACITINIB; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN-6 RECEPTOR ALPHA; MONOCLONAL ANTIBODY; PIPERIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE;

ANTIINFLAMMATORY ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; COMBINATION DRUG THERAPY; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; HUMAN; IMMUNOGENICITY; INFLAMMATION; MONOTHERAPY; PHARMACODYNAMICS; PHENOTYPE; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; STATISTICAL ANALYSIS; STATISTICAL SIGNIFICANCE; METABOLISM; PATHOLOGY;

ADALIMUMAB; ANTIBODIES, MONOCLONAL, HUMANIZED; ARTHRITIS, RHEUMATOID; DRUG THERAPY, COMBINATION; HUMANS; INFLAMMATION; METHOTREXATE; PHENOTYPE; PIPERIDINES; PYRIMIDINES; PYRROLES; RECEPTORS, INTERLEUKIN-6; SIGNAL TRANSDUCTION;

EID: 85048307092     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/s12967-018-1532-5     Document Type: Article

References (35)

1. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1-25.
2. Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509.
3. Burmester GR, Kivitz AJ, Kupper H, Arulmani U, Florentinus S, Goss SL, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis. 2015;74(6):1037-44.
4. Murdaca G, Spano F, Contatore M, Guastalla A, Penza E, Magnani O, et al. Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety? Expert Opin Drug Saf. 2016;15(1):43-52.
5. O'Dell JR. Rheumatoid arthritis. In: Stone JH, editor. A clinician's pearls and myths in rheumatology. New York: Springer; 2016. p. 1-13.
6. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26-37.
7. Klareskog L, Van Der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363(9410):675-81.
8. Bykerk VP, Ostor AJ, Alvaro-Gracia J, Pavelka K, Román Ivorra JA, Graninger W, et al. Comparison of tocilizumab as monotherapy or with add-on disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and inadequate responses to previous treatments: an open-label study close to clinical practice. Clin Rheumatol. 2015;34(3):563-71.
9. Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2year randomized controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013;72(1):43-50.
10. XELJANZ (tofacitinib) tablets for oral administration. New York, NY: Pfizer Labs; 2012.
11. Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381(9865):451-60.
12. Kremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin-Mola E, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013;159(4):253-61.
13. Van Der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559-70.
14. Tanaka Y, Emoto K, Cai Z, Aoki T, Schlichting D, Rooney T, et al. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis receiving background methotrexate therapy: a 12-week, double-blind, randomized placebo-controlled study. J Rheumatol. 2016;43(3):504-11.
15. Genovese MC, van Vollenhoven RF, Pacheco-Tena C, Zhang Y, Kinnman N. VX-509 (decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):46-55.
16. Berg EL, Yang J, Polokoff MA. Building predictive models for mechanism-of-action classification from phenotypic assay data sets. J Biomol Screening. 2013;18(10):1260-9.
17. Berg EL, Kunkel EJ, Hytopoulos E, Plavec I. Characterization of compound mechanisms and secondary activities by BioMAP analysis. J Pharmacol Toxicol Methods. 2006;53(1):67-74.
18. Ciceri P, Muller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, et al. Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. Nat Chem Biol. 2014;10(4):305-12.
19. Berg EL, Kunkel EJ, Hytopoulos E. Biological complexity and drug discovery: a practical systems biology approach. Syst Biol. 2005;152(4):201-6.
20. Kunkel EJ, Dea M, Ebens A, Hytopoulos E, Melrose J, Nguyen D, et al. An integrative biology approach for analysis of drug action in models of human vascular inflammation. FASEB J. 2004;18(11):1279-81.
21. Kunkel EJ, Plavec I, Nguyen D, Melrose J, Rosler ES, Kao LT, et al. Rapid structure-activity and selectivity analysis of kinase inhibitors by BioMAP analysis in complex human primary cell-based models. Assay Drug Dev Tech. 2004;2(4):431-41.
22. Houck KA, Dix DJ, Judson RS, Kavlock RJ, Yang J, Berg EL. Profiling bioactivity of the ToxCast chemical library using BioMAP primary human cell systems. J Biomol Screen. 2009;14(9):1054-66.
23. Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, et al. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012;341(1):90-103.
24. Bergamini G, Bell K, Shimamura S, Werner T, Cansfield A, Müller K, et al. A selective inhibitor reveals PI3Kgamma dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012;8(6):576-82.
25. Melton AC, Melrose J, Alajoki L, Privat S, Cho H, Brown N, et al. Regulation of IL-17A production is distinct from IL-17F in a primary human cell co-culture model of T cell-mediated B cell activation. PLoS ONE. 2013;8(3):e58966.
26. Berg EL, Yang J, Melrose J, Nguyen D, Privat S, Rosler E, et al. Chemical target and pathway toxicity mechanisms defined in primary human cell systems. J Pharmacol Toxicol Methods. 2010;61(1):3-15.
27. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011;1813(5):878-88.
28. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003;374(pt 1):1-20.
29. Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8(9):1227-36.
30. Shiozawa K, Tanaka Y, Yoshihara R, Imura S, Murata M, Yamane T, et al. Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week. Mod Rheumatol. 2005;15(6):405-9.
31. Thoma G, Nuninger F, Falchetto R, Hermes E, Tavares GA, Vangrevelinghe E, et al. Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family. J Med Chem. 2011;54(1):284-8.
32. Dymock BW, See CS. Inhibitors of JAK2 and JAK3: an update on the patent literature 2. Expert Opin Ther Patents. 2013;23(4):449-501.
33. Flanagan ME, Blumenkopf TA, Brissette WH, Brown MF, Casavant JM, Shang-Poa C, et al. Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J Med Chem. 2010;53(24):8468-84.
34. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 2004;50(4):1051-65.
35. Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013;381:1541-50.