THU0203 Changes in c-reactive protein and lipid levels in patients with rheumatoid arthritis treated with abt-494, a selective jak-1 inhibitor
Authors: M Nurmohamed, Y Zhang, J Lin, H Camp
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In patients (pts) with rheumatoid arthritis (RA) treated with ABT-494, dose-dependent increases in levels of low and high density lipoprotein cholesterol (LDL-C and HDL-C) were observed, along with decreases in levels of C-reactive Protein (CRP). Whether these changes are due to the control of inflammation or a direct effect on CRP production in the liver is not known. <h3>Objectives</h3> To explore the relationship between changes in HDL-C or LDL-C and CRP with ABT-494 treatment, and to assess whether the effect on lipids is dependent on improvement of RA signs and symptoms. <h3>Methods</h3> Data were from two phase 2b controlled trials of ABT-494 in RA pts with inadequate response or intolerance to TNF inhibitors (TNF-IR, BALANCE-1)<sup>1</sup>, or with inadequate response to methotrexate (MTX-IR, BALANCE-2)<sup>2</sup>. Pts treated with placebo or 3,6,12,18 mg ABT-494 twice daily for 12 weeks (wks) are included. Levels of high sensitivity (hs) CRP, total cholesterol (TC), LDL-C and HDL-C were measured at baseline (BL) and Wk 2,4,6, 8 and 12. Atherogenic burden at BL and Wk 12 was assessed by ratio of ApoB:ApoA1 and TC:HDL-C in 6 mg and 12 mg dose groups in both studies. Pearson9s coefficients were calculated <i>post hoc</i> to assess possible correlations between HDL-C or LDL-C levels (or changes from BL) with other variables including (high sensitivity) hsCRP, at BL and Wk 12. Pts were subgrouped by response: Sustained responders (SR), pts who achieved an ACR20 response at every visit from Wk 2–12; Responders (R), pts who achieved ACR20 at least once, but not at every visit; Non-responders (NR), pts who did not achieve ACR20 at any visit. <h3>Results</h3> The ratios of LDL-C:HDL-C<sup>1,2</sup> and TC:HDL-C remained unchanged after 12 wks of treatment with ABT-494. The ratio of ApoB:ApoA1 also remained unchanged from BL to Wk 12: in BALANCE-1, 0.61 to 0.58 for the 6 mg (n=19), and 0.62 to 0.60 for 12 mg (n=11) groups, and in BALANCE-2, 0.62 to 0.64 for the 6 mg (n=18) and 0.69 to 0.66 for 12 mg (n=16) groups. An inverse relationship between LDL-C or HDL-C and hsCRP was observed throughout the treatment period. At Wk 4, among the variables tested, the strongest correlation was observed between changes from BL in hsCRP and LDL-C (-0.29, <i>p</i>&lt;0.001) or HDL-C (-0.26, <i>p</i>&lt;0.001). Out of 420 pts, 104 pts (25%) were ACR20 SR, 251 pts (60%) were R and 65 pts (15%) were NR. Compared to NR, SR and R had a greater absolute reduction in hsCRP (Fig. 1A). A robust percentage increase in HDL-C was observed in all 3 groups (20.8%, 18.5% and 16.4% in SR, R and NR, respectively). Compared to the SR and R (14.6% and 16%, respectively), a smaller percentage increase in LDL-C was observed in the NR (8.9%) (Fig. 1B). <h3>Conclusions</h3> Atherogenic burden did not increase in pts treated with ABT-494 for 12 wks. Compared to non-responders, pts with a clinical response experienced a larger increase in lipids and a larger decrease in hsCRP. Limited data from these phase 2 studies suggest that there might not be an increased risk of cardiovascular events. Results from the larger phase 3 trials can provide more information. <h3>References</h3> Kremer et al. 2016, Arthritis &amp; Rheum;68:2867. Genovese et al. 2016, Arthritis &amp; Rheum;68:2857. <h3>Acknowledgements</h3> AbbVie: study sponsor, contributed to study design, data collection, analysis and interpretation; writing, reviewing, and approval of the final version. Medical writing: Naina Barretto, of AbbVie. <h3>Disclosure of Interest</h3> M. Nurmohamed Grant/research support from: Abbvie, Bristol–Myers Squibb, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Janssen, UCB and Sanofi., Consultant for: Abbvie, Bristol–Myers Squibb, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Janssen, UCB and Sanofi., Y. Zhang Employee of: AbbVie, J. Lin Employee of: AbbVie, H. Camp Employee of: AbbVie