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.

Abstract

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.

• Authors: Laurence E Cheng, Zahir Amoura, Benjamin Cheah, Falk Hiepe, Barbara A Sullivan, Lei Zhou, Gregory E Arnold, Wayne H Tsuji, Joan T Merrill, James B Chung
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 70 Issue 7 Pg. 1071-1076 (07 2018) ISSN: 2326-5205 [Electronic] United States
• PMID: 29513931 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Chemical References

• AMG 557
• Adrenal Cortex Hormones
• Antibodies, Monoclonal, Humanized
• Immunosuppressive Agents
• Inducible T-Cell Co-Stimulator Ligand

Topics

• Adolescent
• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, immunology)
• Arthritis (drug therapy, immunology, pathology)
• Double-Blind Method
• Female
• Humans
• Immunosuppressive Agents (therapeutic use)
• Inducible T-Cell Co-Stimulator Ligand (immunology)
• Joints (drug effects, pathology)
• Lupus Erythematosus, Systemic (drug therapy, immunology, pathology)
• Male
• Middle Aged
• Severity of Illness Index
• Treatment Outcome
• Young Adult