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AMG 811 may impact biomarkers of disease in patients with SLE
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Dose-related inhibition of interferon-regulated gene expression and reduced serum CXCL10 levels were observed in patients with systemic lupus erythematosus treated with AMG 811, according to the results of an investigational study.
Researchers recruited 26 patients with fibromyalgia into a randomized, double-blind, placebo-controlled, single-dose escalation study. Patients were randomized to a single, subcutaneous dose of either 2, 6, 20, 60 or 180 mg of AMG 811 (Amgen), 180-mg IV AMG 811 (n = 18; three in each group) or placebo (n = 8). Concomitant antimalarial drugs, leflunomide, azathioprine, methotrexate and up to 20 mg per day of prednisone equivalent were permitted. Patients were followed for a minimum of 84 days and up to 196 days following treatment.
Blood samples were collected from the patients at baseline and on day 1 prior to receiving the dose, and at day 15, day 56 and at the end of the study. Blood from four healthy volunteers was collected and analyzed to compare gene expression. Compared to healthy volunteers, serum levels of interleukin-18 (IL-18), CXCL10, CCL2 and RANTES were elevated in patients with SLE. At day 15, following administration of AMG 811, a decrease in CXCL10 was observed at day 15, while levels returned toward baseline levels by day 56. No changes were observed with IL-18, CCL2 or RANTES.
Some genes that overlapped with the top 20 genes stimulated by interferon- were downregulated following treatment with AMG 811. A change in gene expression which tended to correlate with dose was observed in patients after treatment, particularly with guanylate binding protein 1 (GBP-1) at day 15. Inconsistent changes in expression were observed in some patients in the placebo group and the changes did not vary between study dates on average. A decline in GBP-1 was seen in all patients treated with AMG 811. No correlation was seen with interferon-γ.
According to the researchers, treatment with AMG 811 was well tolerated with no withdrawals due to adverse events and no deaths occurred. One serious adverse event occurred in a patient who received 60-mg AMG 811 and was treated with IV antibiotics for pyelonephritis about 3 months after treatment.
“Modulation of dysregulated biomarkers by AMG 811 in SLE patients, and restoration toward the levels seen in healthy subjects, supports continued investigation of the clinical consequences of interferon- blockade,” the researchers concluded. – by Shirley Pulawski
Disclosure: Welcher owns stock in Amgen and is a coinventor of AMG 811. Please see the full study for a list of all other authors’ relevant financial disclosures.
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