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Brief Report: A Randomized, Double‐Blind, Parallel‐Group, Placebo‐Controlled, Multiple‐Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis
Author(s) -
Cheng Laurence E.,
Amoura Zahir,
Cheah Benjamin,
Hiepe Falk,
Sullivan Barbara A.,
Zhou Lei,
Arnold Gregory E.,
Tsuji Wayne H.,
Merrill Joan T.,
Chung James B.
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40479
Subject(s) - medicine , double blind , placebo , systemic lupus erythematosus , arthritis , placebo controlled study , lupus erythematosus , randomized controlled trial , immunology , antibody , pathology , disease , alternative medicine
Objective To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus ( SLE ) with arthritis. Methods In this phase Ib, randomized, double‐blind, placebo‐controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index ( LARI ; defined by a reduction in the tender and swollen joint counts), ≥1‐letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group ( BILAG ) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index ( SLEDAI ). Results The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo ( P = 0.58). More patients in the AMG 557 group achieved a ≥4‐point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) ( P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (–36.3% versus –24.7%) and the SLEDAI score (–47.8% versus –10.7%) and in tender (–22.8% versus –13.5%) and swollen (–62.1% versus –7.8%) joint counts on day 169. Conclusion AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE .