ICOS ligand blockade a promising approach for the treatment of lupus arthritis
AMG-557, an inducible T-cell costimulator (ICOS) ligand inhibitor, showed efficacy and safety in a randomized multicentre trial that included patients with lupus arthritis from eight centres in the US, France, Malaysia and Germany.
In this double-blind, randomized, placebo-controlled study that included 20 patients (95 percent female), those who received AMG-557 demonstrated better composite Lupus Arthritis Responder Index vs placebo recipients (30 vs 10 percent; p=ns). [EULAR 2017, abstract OP0234]
Response was defined as achieving 50 percent decrease in combined tender and swollen joint counts, and ≥1 letter improvement in the musculoskeletal subsystem of the British Isles Lupus Assessment Group (BILAG) index and prespecified immunosuppressant medication withdrawal and/or prednisone taper.
“Withdrawal of background immunosuppressants was done to isolate treatment effect,” said Laurence E. Cheng, Medical Director at Amgen, Thousand Oaks, California, US, one of the authors of the study, who presented the trial findings at the European League Against Rheumatism (EULAR) Annual Congress 2017 held recently in Madrid, Spain. [Arthritis Rheumatol 2017;69:1257-1266]
Mean percentage change in global BILAG index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was also greater in patients who received AMG-557 vs placebo (BILAG, -36 vs -23 percent; SLEDAI, -48 vs -11 percent).
Furthermore, a greater proportion of patients who received AMG-557 achieved 4-point reduction of SLEDAI vs placebo recipients (70 vs 20 percent).
Lupus-associated biomarkers, including increased serum complement indices (C3, C4, and CH50), and decreased anti-double stranded deoxyribonucleic acid (dsDNA), demonstrated trends towards improvement with AMG-557 relative to placebo, consistent with the clinical findings.
“In terms of safety, treatment-emergent adverse effects were similar in those receiving AMG-557 and placebo. Most adverse events are grade 1 or 2, such as headache and upper respiratory tract infection. No grade 4 adverse events or death occurred,” Cheng said.
“AMG-557, when given to patients with lupus arthritis, showed no new safety signals with its action of ICOSL blockade. Preliminary clinical and biomarker profiles in response to treatment are also promising. The only caveat is that interpretation of data in this study is limited due to the small number of patients,” concluded Cheng.
ICOS ligand (ICOSL) is expressed on both antigen presenting cells and B-cells. Thus, interrupting ICOS-ICOSL interaction results in interference of T follicular helper cell function and decreased autoantibody production.
AMG-557 is a human immunoglobulin G2 monoclonal antibody that has recently demonstrated safety, with dose-proportional pharmacokinetics at doses above 70 mg and pharmacodynamic effects consistent with the biology of the ICOS pathway. [ACR 2013, abstract 1743]