Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus

Arthritis and Rheumatology

Volumn 69, Issue 5, 2017, Pages 1028-1034

  Werth, Victoria P ^a   Fiorentino, David ^b   Sullivan, Barbara A ^c   Boedigheimer, Michael J ^c   Chiu, Kit ^c   Wang, Christine ^c   Arnold, Gregory E ^c   Damore, Michael A ^c   Bigler, Jeannette ^d   Welcher, Andrew A ^c   Russell, Chris B ^d   Martin, David A ^d   Chung, James B ^c  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b STANFORD UNIVERSITY   (United States)

^c AMGEN INC   (United States)

^d AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMG 811; ANTIMALARIAL AGENT; GAMMA INTERFERON; GAMMA INTERFERON ANTIBODY; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 17; INTERLEUKIN 22; PREDNISONE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; CXCL10 PROTEIN, HUMAN; IMMUNOSUPPRESSIVE AGENT; MESSENGER RNA; MONOCLONAL ANTIBODY;

ADULT; ARTHRALGIA; ARTICLE; CLINICAL ARTICLE; CLINICAL OUTCOME; CONTROLLED STUDY; CROSSOVER PROCEDURE; DISCOID LUPUS ERYTHEMATOSUS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GASTROENTERITIS; GENE EXPRESSION PROFILING; HEADACHE; HUMAN; HYPERTRIGLYCERIDEMIA; IN VITRO STUDY; KERATINOCYTE; MALE; MIDDLE AGED; MIGRAINE; MULTICENTER STUDY; PHASE 1 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; SLEDAI; SPLEEN INFARCTION; SUBDURAL HEMATOMA; UPPER RESPIRATORY TRACT INFECTION; VIRAL GASTROENTERITIS; CLINICAL TRIAL; GENETICS; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, DISCOID; METABOLISM; TREATMENT OUTCOME;

ADULT; ANTIBODIES, MONOCLONAL; CHEMOKINE CXCL10; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERFERON-GAMMA; LUPUS ERYTHEMATOSUS, DISCOID; MALE; MIDDLE AGED; RNA, MESSENGER; TREATMENT OUTCOME;

EID: 85017333821     PISSN: 23265191     EISSN: 23265205     Source Type: Journal    
DOI: 10.1002/art.40052     Document Type: Article

References (17)

1. Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981;4:471–5.
2. Fabbri P, Cardinali C, Giomi B, Caproni M. Cutaneous lupus erythematosus: diagnosis and management. Am J Clin Dermatol 2003;4:449–65.
3. Achtman JC, Werth VP. Pathophysiology of cutaneous lupus erythematosus. Arthritis Res Ther 2015;17:182.
4. Toro JR, Finlay D, Dou X, Zheng SC, LeBoit PE, Connolly MK. Detection of type 1 cytokines in discoid lupus erythematosus. Arch Dermatol 2000;136:1497–501.
5. Shirakata Y. Regulation of epidermal keratinocytes by growth factors. J Dermatol Sci 2010;59:73–80.
6. Wenzel J, Uerlich M, Worrenkamper E, Freutel S, Bieber T, Tuting T. Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA. Br J Dermatol 2005;153:1011–5.
7. Chen P, Vu T, Narayanan A, Sohn W, Wang J, Boedigheimer M, et al. Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-γ IgG1 monoclonal antibody, in patients with systemic lupus erythematosus. Pharm Res 2015;32:640–53.
8. Welcher AA, Boedigheimer M, Kivitz AJ, Amoura Z, Buyon J, Rudinskaya A, et al. Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. Arthritis Rheumatol 2015;67:2713–22.
9. Werth VP, Fiorentino D, Cohen SB, Fivenson D, Hansen C, Zoog S, et al. A phase I single-dose crossover study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical efficacy of AMG 811 (anti-IFN-gamma) in patients with discoid lupus erythematosus [abstract]. Arthritis Rheum 2013;65 Suppl:S682.
10. Martin DA, Amoura Z, Romero-Diaz J, Chong YB, Sanchez-Guerrero J, Chan T, et al. A multiple dose study of AMG 811 (anti-IFN-gamma) in patients with systemic lupus erythematosus and active nephtiris [abstract]. Ann Rheum Dis 2015;74:337.
11. Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Suarez-Farinas M, Cardinale I, et al. Th17 cytokines interleukin (IL)–17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol 2008;159:1092–102.
12. Albrecht J, Taylor L, Berlin JA, Dulay S, Ang G, Fakharzadeh S, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 2005;125:889–94.
13. Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol 2002;29:288–91.
14. Dey-Rao R, Sinha AA. Genome-wide transcriptional profiling of chronic cutaneous lupus erythematosus (CCLE) peripheral blood identifies systemic alterations relevant to the skin manifestation. Genomics 2015;105:90–100.
15. Braunstein I, Klein R, Okawa J, Werth VP. The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score. Br J Dermatol 2012;166:971–5.
16. Kreuter A, Tomi NS, Weiner SM, Huger M, Altmeyer P, Gambichler T. Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy. Br J Dermatol 2007;156:1321–7.
17. Shah A, Albrecht J, Bonilla-Martinez Z, Okawa J, Rose M, Rosenbach M, et al. Lenalidomide for the treatment of resistant discoid lupus erythematosus. Arch Dermatol 2009;145:303–6.