Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: LNK01001 is a selective oral JAK1 inhibitor in clinical development for treating autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). Here, we report the 24-week efficacy and safety results of LNK01001 in patients with moderate to severe active RA who had an inadequate response to csDMARDs.
Methods: Eligible participants aged 18 to 75 with a diagnosis of moderate to severe active RA who met ACR/EULAR 2010 criteria and had an inadequate response to csDMARDs, were randomized (1: 1: 1) to receive LNK01001 12mg or 24mg twice daily (BID), or placebo for 12 weeks, followed by a 12-week extension treatment with LNK01001 12mg or 24mg. The primary endpoint was the proportion of patients achieving an ACR20 response at Week 12.
Results: All 156 patients randomized were included in the analysis. The mean age was 52.4 years, and 76.9% were female, mean DAS28-CRP score was 5.884. Baseline characteristics were similar across treatment groups. At week 12, a significantly higher proportion of patients achieved ACR20, ACR50 and ACR70 in LNK01001 12 mg and 24 mg groups compared with the placebo group (ACR20: 60.0% [95%CI: 45.2, 73.6], 73.1% [95%CI: 59.0, 84.4], vs 31.5% [95%CI: 19.5, 45.6], both doses p< 0.01; ACR50: 40.0% [95%CI: 26.4, 54.8], 42.3% [95%CI: 28.7, 56.8], vs 9.3% [95%CI: 3.1, 20.3], both doses p< 0.001; and ACR70: 12.0% [95%CI: 4.5, 24.3], 23.1% [95%CI: 12.5, 36.8], vs 1.9% [95%CI: 0.0, 9.9], both doses p < 0.05). A statistically significant difference was reached as early as Week 1 in ACR20 for both doses of LNK01001 vs placebo (18.0% [95%CI: 8.6, 31.4], 23.1% [95%CI: 12.5, 36.8], vs 0% [95%CI: 0, 6.6], both doses p＜0.01). Disease activity reduction measured by DAS28-CRP and functional ability improvement of HAQ-DI were significant in patients treated with LNK01001 compared to patients treated with placebo (-2.518, -2.614, vs -1.263, both doses p＜0.0001; and -0.64, -0.73, vs -0.34, both doses P < 0.01). During extension treatment, the proportion of patients achieving ACR20/50/70, DAS28 (≤ 3.2 and < 2.6), SDAI (≤ 11 and ≤ 3.3) and CDAI (≤ 10 and ≤ 2.8) response increased steadily over time. At week 24, 91.1% (95%CI: 78.8, 97.5) and 90.7% (95%CI: 77.9, 97.4) of patients achieved ACR20 in LNK01001 12mg and 24mg group, respectively.
The most frequently reported TEAE in patients receiving LNK01001 was hyperlipidemia. No serious infection, malignancy, venous thromboembolism or major adverse cardiovascular events were reported up to 24 weeks.
Conclusion: Treatment with LNK01001 12 mg or 24 mg BID up to 24 weeks in patients with moderate to severe active RA and an inadequate response to csDMARDs were generally safe, and well tolerated with most TEAEs being mild to moderate. Both doses were superior to placebo in reducing the severity of rheumatoid arthritis over a period of 12 weeks across multiple efficacy end points.
To cite this abstract in AMA style:Wu C, Wang X, Hu J, Shi X, Wang X, Zhang X, Liu J, Rao H, Zhao J, Du R, Jiang Z, liu H, Liu L, Liu S, Xie C, Liao X, Dai L, Hou Z, Jin J, Li T, Meng D, Wang Y, Wu J, Gu J, Wei W, Zhuang Y, Wang K, Zhang R, Zhang X, Wei H, Wan Z, Wang J, Vazquez M, Wu H, Zeng X. Efficacy and Safety of LNK01001 in Chinese Patients with Moderate to Severe Active Rheumatoid Arthritis with an Inadequate Response to Conventional Synthetic DMARDs: 24-week Results from a Phase 2 Trial [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-lnk01001-in-chinese-patients-with-moderate-to-severe-active-rheumatoid-arthritis-with-an-inadequate-response-to-conventional-synthetic-dmards-24-week-results-from-a-phase-2-tri/. Accessed .
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