Sarilumab Significantly Increases Cholesterol vs. Placebo in Patients with RA
SAN DIEGO, CA—Sarilumab 150mg and 200mg administered every other week significantly increased levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) in patients with rheumatoid arthritis (RA), according to results of a 12-week study presented at the 2013 ACR/ARHP Annual Meeting.
These increases were associated with baseline inflammation levels and degree of suppression of inflammation by sarilumab, a fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor currently being investigated for the treatment of RA, Christina Charles-Schoeman, MD, of UCLA David Geffen School of Medicine, Los Angeles, CA, and colleagues found.
The investigators utilized data from the Phase 2 MOBILITY Part A study to evaluate the relationship between cholesterol levels and measures of inflammation in 306 patients with RA randomized to one of 6 treatment groups: placebo; sarilumab 100mg, 150mg, or 200mg every other week or sarilumab 100mg or 150mg weekly.
Changes from baseline to Week 12 in total cholesterol, LDL-C, high density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), and serum amyloid A (SAA) levels were assessed according to tertiles of baseline CRP and SAA levels in the two sarilumab whole dose regimen groups selected for study in Phase 3 trials (150mg and 200mg every other week).
At Week 12, changes in total cholesterol and LDL-C but not HDL-C were statistically significantly greater in patients treated with SAR compared to placebo (both P<0.05). The largest decreases in inflammation and the largest increases in TC with sarilumab treatment were observed in patients with the highest baseline levels of inflammation. Similar trends were observed for LDL-C.
“Individuals with the greatest levels of suppression of SAA and CRP also had the highest levels of total cholesterol and LDL-C,” they reported.
The most common treatment-emergent adverse event in all sarilumab arms was non-serious infection (range, 12—26%). None of the 8 patients who experienced at least one treatment-emergent serious adverse event were in the sarilumab 150mg of 200mg every other week or placebo arms; however, 6 permanently discontinued treatment.“Further investigation of additional CV biomarkers which are less sensitive to the acute phase response and adequately assess CV risk in the setting of high levels of systemic inflammation from active RA may be warranted,” the researchers wrote. The effect of sarilumab on cholesterol levels and CV risk in patients with RA will be further evaluated in the Phase 3 program.