A5.10Increases in serum cholesterol with baricitinib treatment are associated with favourable changes in apolipoprotein content and with improvement in DAS28-CRP in patients with rheumatoid arthritis

Treatment with baricitinib (bari), an oral inhibitor of JAK1/JAK2, demonstrated improvements in signs and symptoms of RA through 52 wks in a Phase 2b study,1 and also in dose- and time-dependent changes in serum lipids, LDL particle size and HDL and VLDL particle numbers.2 Increases in HDL, but not LDL cholesterol, correlated with decreases in CRP at Wk 12. Changes in serum cholesterol, in apolipoprotein content of LDL, VLDL, and HDL particles were evaluated.Patients (pts) with RA were randomised to QD doses of placebo (PBO) (n = 98) or bari 1 mg (n = 49), 2 mg (n = 52), 4 mg (n = 52), or 8 mg (n = 50) for 12 wks. Pts assigned to 2-, 4-, or 8-mg bari continued blinded treatment for an additional 12 wks. Serum samples were collected through 52 wks for conventional lipid determinations (total cholesterol, LDL, HDL, and triglycerides). Apolipoprotein content was assessed at Wks 4 and 12 for PBO, 4-, and 8-mg bari groups.Pts treated with bari through 52 wks maintained a stable cholesterol and triglyceride profile with no further changes beyond Wks 12 and 24. Increases in apolipoprotein A-I, apolipoprotein B, and total apolipoprotein CIII were observed with 4- and 8-mg bari with no increase in LDL-associated apolipoprotein CIII. Bari treatment also demonstrated a significant reduction in HDL-associated SAA at the 4- and 8-mg doses compared to PBO while a significant reduction in Lp (a) was observed only in the 8-mg bari group (all p < 0.05). These changes in apolipoproteins coincided with the increases in serum lipids apparent by Wk 4. In pts treated across all doses of bari, a significant correlation was observed between change in HDL cholesterol and absolute DAS28-CRP score at Wk 12 (r = -0.33, p < 0.001) as well as the change from baseline to Wk 12 in the DAS28-CRP (r = -0.29, p < 0.001). Specifically, pts achieving DAS28-CRP