Phase II Study of ABT-122, a Tumor Necrosis Factor– and Interleukin-17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

Arthritis and Rheumatology

Volumn 70, Issue 11, 2018, Pages 1778-1789

  Mease, Philip J ^a   Genovese, Mark C ^b   Weinblatt, Michael E ^c   Peloso, Paul M ^d   Chen, Kun ^d   Othman, Ahmed A ^d   Li, Yihan ^d   Mansikka, Heikki T ^d   Khatri, Amit ^d   Wishart, Neil ^d   Liu, John ^d  

^a UNIVERSITY OF WASHINGTON   (United States)

^b STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d ABBVIE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; INTERLEUKIN 17; METHOTREXATE; PLACEBO; REMTOLUMAB; TUMOR NECROSIS FACTOR; ABT-122; ANTIRHEUMATIC AGENT; IL17A PROTEIN, HUMAN; IMMUNOGLOBULIN; TNF PROTEIN, HUMAN;

ADULT; ARTICLE; CONTROLLED STUDY; DISEASE ACTIVITY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; FAINTNESS; FEMALE; HUMAN; INFECTION; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; NEUTROPENIA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PSORIASIS AREA AND SEVERITY INDEX; PSORIATIC ARTHRITIS; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SICK SINUS SYNDROME; THRUSH; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; TREATMENT OUTCOME;

ADULT; ANTIRHEUMATIC AGENTS; ARTHRITIS, PSORIATIC; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOGLOBULINS; INTERLEUKIN-17; MALE; METHOTREXATE; MIDDLE AGED; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 85054612048     PISSN: 23265191     EISSN: 23265205     Source Type: Journal    
DOI: 10.1002/art.40579     Document Type: Article

References (52)

1. De Vlam K, Gottlieb AB, Mease PJ. Current concepts in psoriatic arthritis: pathogenesis and management. Acta Derm Venereol 2014;94:627–34.
2. Mease PJ. Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002;61:298–304.
3. Ritchlin C, Haas-Smith SA, Hicks D, Cappuccio J, Osterland CK, Looney RJ. Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998;25:1544–52.
4. Partsch G, Steiner G, Leeb BF, Dunky A, Broll H, Smolen JS. Highly increased levels of tumor necrosis factor-α and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J Rheumatol 1997;24:518–23.
5. Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008;58:2307–17.
6. Leipe J, Grunke M, Dechant C, Reindl C, Kerzendorf U, Schulze-Koops H, et al. Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 2010;62:2876–85.
7. Raychaudhuri SP, Raychaudhuri SK, Genovese MC. IL-17 receptor and its functional significance in psoriatic arthritis. Mol Cell Biochem 2012;359:419–29.
8. Mease PJ. Inhibition of interleukin-17, interleukin-23 and the TH17 cell pathway in the treatment of psoriatic arthritis and psoriasis. Curr Opin Rheumatol 2015;27:127–33.
9. Menon B, Gullick NJ, Walter GJ, Rajasekhar M, Garrood T, Evans HG, et al. Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression. Arthritis Rheumatol 2014;66:1272–81.
10. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;50:2264–72.
11. Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:3279–89.
12. Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med 2014;370:2295–306.
13. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med 2015;373:1329–39.
14. Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 2017;76:79–87.
15. Antoni C, Krueger GG, de Vlam K, Birbara C, Beutler A, Guzzo C, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005;64:1150–7.
16. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, et al. Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009;60:976–86.
17. Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy. Arthritis Res Ther 2011;13:R126.
18. Hull DN, Williams RO, Pathan E, Alzabin S, Abraham S, Taylor PC. Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis. Clin Exp Immunol 2015;181:401–6.
19. Chabaud M, Miossec P. The combination of tumor necrosis factor α blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 2001;44:1293–303.
20. Sakellariou GT, Sayegh FE, Anastasilakis AD, Kapetanos GA. Leflunomide addition in patients with articular manifestations of psoriatic arthritis resistant to methotrexate. Rheumatol Int 2013;33:2917–20.
21. Fraser AD, van Kuijk AW, Westhovens R, Karim Z, Wakefield R, Gerards AH, et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann Rheum Dis 2005;64:859–64.
22. Baranauskaite A, Raffayova H, Kungurov N, Kubanova A, Venalis A, Helmle L, et al. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study. Ann Rheum Dis 2012;71:541–8.
23. Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 2004;50:1412–9.
24. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheum 2006;54:2807–16.
25. Weinblatt M, Schiff M, Goldman A, Kremer J, Luggen M, Li T, et al. Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis 2007;66:228–34.
26. Greenwald MW, Shergy WJ, Kaine JL, Sweetser MT, Gilder K, Linnik MD. Evaluation of the safety of rituximab in combination with a tumor necrosis factor inhibitor and methotrexate in patients with active rheumatoid arthritis: results from a randomized controlled trial. Arthritis Rheum 2011;63:622–32.
27. Hsieh CM, Cuff C, Tarcsa E, Hugunin M. FRI0303 discovery and characterization of ABT-122, an anti-TNF/IL-17 DVD-IG molecule as a potential therapeutic candidate for rheumatoid arthritis [abstract]. Ann Rheum Dis 2014;7 Suppl:495.
28. Mansikka H, Ruzek M, Hugunin M, Ivanov A, Brito A, Clabbers A, et al. FRI0164 safety, tolerability, and functional activity of ABT-122, a dual TNF- and IL-17A–targeted DVD-IG, following single-dose administration in healthy subjects [abstract]. Ann Rheum Dis 2015;74 Suppl 2:482–3.
29. Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK, et al. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol 2009;131:308–16.
30. Liu L, Lu J, Allan BW, Tang Y, Tetreault J, Chow CK, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res 2016;9:39–50.
31. Khatri A, Goss S, Jiang P, Mansikka H, Othman AA. Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-targeted dual-variable domain immunoglobulin, in healthy subjects and patients with rheumatoid arthritis: results from three phase I trials. Clin Pharmacokinet 2018;57:613–23.
32. Fleischmann RM, Wagner F, Kivitz AJ, Mansikka HT, Khan N, Othman AA, et al. Safety, tolerability, and pharmacodynamics of ABT-122, a TNF– and IL-17–targeted dual variable domain immunoglobulin, in patients with rheumatoid arthritis. Arthritis Rheumatol 2017;69:2283–91.
33. Genovese MC, Weinblatt M, Aelion JA, Mansikka HT, Peloso PM, Chen K, et al. ABT-122, a bispecific dual variable domain immunoglobulin targeting tumor necrosis factor and interleukin-17A, in patients with rheumatoid arthritis with an inadequate response to methotrexate. Arthritis Rheumatol 2018;70:1710–20.
34. Genovese MC, Weinblatt ME, Mease PJ, Aelion JA, Peloso PM, Chen K, et al. Dual inhibition of tumour necrosis factor and interleukin-17A with ABT-122: open-label long-term extension studies in rheumatoid arthritis or psoriatic arthritis. Rheumatology (Oxford) 2018. E-pub ahead of print.
35. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665–73.
36. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727–35.
37. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight–joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8.
38. Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica 1978;157:238–44.
39. Daltroy LH, Larson MG, Roberts NW, Liang MH. A modification of the Health Assessment Questionnaire for the spondyloarthropathies. J Rheumatol 1990;17:946–50.
40. Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis 2009;68:948–53.
41. Woodworth T, Furst DE, Alten R, Bingham CO III, Yocum D, Sloan V, et al. Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v. 2.0. J Rheumatol 2007;34:1401–14.
42. Khatri A, Othman AA. Population pharmacokinetics of the TNF-α and IL-17A dual-variable domain antibody ABT-122 in healthy volunteers and subjects with psoriatic or rheumatoid arthritis: analysis of phase 1 and 2 clinical trials. J Clin Pharmacol 2018;58:803–13.
43. Taltz (ixekizumab) prescribing information. Indianapolis (IN): Eli Lilly and Company; 2016.
44. Cosentyx (secukinumab) prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation; 2016.
45. Georgantas RW, Ruzek M, Davis JW, Hong F, Asque E, Idler K, et al. Genomic and epigenetic bioinformatics demonstrate dual TNF-α and IL17a target engagement by ABT-122, and suggest mainly TNF-α–mediated relative target contribution to drug response in MTX-IR rheumatoid arthritis patients [abstract]. Arthritis Rheumatol 2016;68 Suppl 10. URL: http://acrabstracts.org/abstract/genomic-and-epigenetic-bioinformatics-demonstrate-dual-tnf-%CE%B1-and-il17a-target-engagement-by-abt-122-and-suggest-mainly-tnf-%CE%B1-mediated-relative-target-contribution-to-drug-response-i/.
46. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med 2014;371:326–38.
47. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 2016;375:345–56.
48. Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Mazurov V, 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.
49. Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol 2015;42:912–9.
50. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008;128:1207–11.
51. Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, et al. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 2009;129:2175–83.
52. Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 2009;160:319–24.