Background/Purpose:

Sarilumab showed superiority to placebo and adalimumab in Phase 3 trials. Serum lipids may be reduced in the setting of chronic inflammation associated with active RA and may increase following effective response to RA therapy. In this post hoc analysis we investigated the relationship between lipid levels and markers of inflammation.

Methods:

Fasting total, HDL and LDL cholesterol, triglycerides, lipoprotein (a) (Lp(a)), and apolipoproteins (Apo) A and B were evaluated in two placebo-controlled studies of sarilumab (150 mg and 200 mg q2w) +csDMARDs in patients with inadequate response to MTX (MOBILITY; NCT01061736) or intolerance or inadequate response to TNF inhibitors (TARGET; NCT01709578) and a monotherapy study of sarilumab vs adalimumab (MONARCH; NCT02332590). Spearman and Pearson correlations compared relationships between lipid levels and inflammatory markers (CRP and SAA [MOBILITY only]).

Results:

Safety has been previously reported with no evidence of increased risk of major adverse cardiac events with sarilumab.^1–3 In 52-wk MOBILITY (Figure) and 24-wk TARGET, both sarilumab doses led to increases in total cholesterol, HDL-C, LDL-C, and triglyceride levels vs placebo (as early as Wk 2), which were maintained throughout the studies. In MONARCH, sarilumab treatment led to a greater mg/dL increase from baseline in total cholesterol (16.3 vs 1.4), HDL-C (1.4 vs –0.2), LDL-C (10.5 vs 0.5), and triglycerides (26.6 vs 5.7) and a greater decrease in Lp(a) (–41% vs –2.8%).⁴ Changes from baseline in total cholesterol/HDL-C ratio for sarilumab 200 mg q2w vs placebo were 0.41 vs 0.01 (MOBILITY Wk 52), 0.32 vs –0.06 (TARGET Wk 24) and vs adalimumab were 0.22 vs 0.02 (Wk 24). Sarilumab reduced CRP and SAA (MOBILITY) vs placebo and adalimumab.⁴ Negative Spearman correlations (P<0.001 or P<0.0001) between decreases from baseline in CRP and increases in lipid levels were seen with sarilumab 200 mg q2w for total cholesterol (–0.26 [MOBILITY Wk 52] and –0.33 [TARGET Wk 24]), HDL-C (–0.26 TARGET Wk 24), LDL-C (–0.21 [MOBILITY Wk 24] and –0.25 [TARGET Wk 24]), and triglycerides (–0.21 [MOBILITY Wk 52]) and with adalimumab (data not shown).

Conclusion:

Sarilumab, an IL-6R blocker recently approved for the treatment of RA, showed an increase in various lipid parameters vs placebo or adalimumab and reduction in Lp(a). This was seen relatively quickly and stabilized after 4 weeks. Lipid elevation was associated with a reduction in inflammatory markers and was consistent with IL-6 blockade.

References

1.     Genovese MC, et al. Arthritis Rheumatol 2015;67:1424–37

2.     Fleischmann R, et al. Arthritis Rheumatol 2017;69:277–90

3.     Burmester GR, et al. Ann Rheum Dis 2017;76:840–7

4.     Gabay C, et al. Ann Rheum Dis 2017;76:570 (Abstract FRI0227)

Acknowledgements

Study funding and medical writing support (Zach Dixon, Adelphi Communications) provided by Sanofi and Regeneron Pharmaceuticals, Inc.