Efficacy and safety of Janus kinase inhibitor for the treatment of patients with axial spondyloarthritis: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

YANG Yibing ¹ , LI Yangming ² ,  LI Jiangtao ³

1. School of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, P. R. China;
2. Department of Urology Surgery, Sichuan Second Hospital of Traditional Chinese Medicine, Chengdu 610031, P. R. China;
3. Department of Rheumatology and Immunology, The First People Hospital of Yibin, Yibin 644000, P. R. China;

Corresponding author：

LI Jiangtao, Email: hxyyljt@163.com

Keywords：

JAK inhibitors; Axial spondyloarthritis; Efficacy; Safety; Meta-analysis

DOI：

10.7507/1672-2531.202403096

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Objective To systematically review the efficacy and safety of JAK inhibitor in the treatment of axial spondyloarthritis (axSpA). Methods The PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of JAK inhibitors in patients with axSpA from inception to December, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies Meta-analysis was then performed using RevMan 5.3 software. Results A total of 7 RCTs involving 1 602 patients were included, including 852 patients in the experimental group and 750 patients in the placebo group. The results of meta-analysis showed that in terms of clinical efficacy, ASAS20 (RR=1.67, 95%CI 1.50 to 1.86, P<0.01), ASAS40 (RR=2.30, 95%CI 1.93 to 2.73, P<0.01), ΔBASFI (MD=−1.04, 95%CI −1.21 to −0.87, P<0.01), and ΔBASMI (MD=−0.30, 95%CI −0.41 to −0.19, P<0.01) of JAK inhibitors in the treatment of axSpA patients were significantly higher than those in the placebo group. In terms of safety, adverse event (RR=1.09, 95%CI 0.97 to 1.21, P=0.14) and major adverse events, such as diarrhea (RR=1.18, 95%CI 0.55 to 2.51, P=0.67), nasopharyngitis (RR=0.98, 95%CI 0.55 to 1.75, P=0.96), liver enzyme abnormalities (RR=1.83, 95%CI 0.84 to 3.99, P=0.13), and headache (RR=1.94, 95%CI 0.77 to 4.87, P=0.16) were statistically insignificant. Conclusion Current evidence shows that JAK inhibitors can improve the clinical efficacy in the axSpA patients, and the safety is high. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

1.	Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet, 2017, 390(10089): 73-84.
2.	Navarro-Compán V, Sepriano A, El-Zorkany B, et al. Axial spondyloarthritis. Ann Rheum Dis, 2021, 80(12): 1511-1521.
3.	Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis, 2009, 68(Suppl 2): 1-44.
4.	López-Medina C, Moltó A. Update on the epidemiology, risk factors, and disease outcomes of axial spondyloarthritis. Best Pract Res Clin Rheumatol, 2018, 32(2): 241-253.
5.	吴珊珊, 段振华, 潘发明. 强直性脊柱炎流行病学研究进展. 安徽医科大学学报, 2013, 48(8): 988-992.
6.	黄烽, 朱剑, 王玉华, 等. 强直性脊柱炎诊疗规范. 中华内科杂志, 2022, 61(8): 893-900.
7.	Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol, 2019, 71(10): 1599-1613.
8.	Danve A, Deodhar A. Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol, 2022, 18(4): 205-216.
9.	Lubrano E, De Socio A, Perrotta FM. Unmet needs in axial spondyloarthritis. Clin Rev Allergy Immunol, 2018, 55(3): 332-339.
10.	Toussirot E. The use of Janus kinase inhibitors in axial spondyloarthritis: current insights. Pharmaceuticals (Basel), 2022, 15(3): 270.
11.	《Janus激酶抑制剂治疗风湿免疫病超药品说明书用药中国专家共识》制定专家组. Janus激酶抑制剂治疗风湿免疫病超药品说明书用药中国专家共识. 中华风湿病学杂志, 2023, 27(1): 1-9.
12.	van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum, 1984, 27(4): 361-368.
13.	Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis, 2009, 68(6): 777-783.
14.	van der Heijde D, Deodhar A, Wei JC, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis, 2017, 76(8): 1340-1347.
15.	Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis, 2021, 80(8): 1004-1013.
16.	姜克悦, 刘磊, 王文惠. 枸橼酸托法替布治疗活动性强直性脊柱炎的随机对照研究. 实用医学杂志, 2022, 38(11): 1415-1418.
17.	van der Heijde D, Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet, 2019, 394(10214): 2108-2117.
18.	van der Heijde D, Baraliakos X, Sieper J, et al. Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial. Ann Rheum Dis, 2022, 81(11): 1515-1523.
19.	van der Heijde D, Baraliakos X, Gensler LS, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet, 2018, 392(10162): 2378-2387.
20.	Deodhar A, Van den Bosch F, Poddubnyy D, et al. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2022, 400(10349): 369-379.
21.	Winthrop KL, Cohen SB. Oral surveillance and JAK inhibitor safety: the theory of relativity. Nat Rev Rheumatol, 2022, 18(5): 301-304.
22.	Mattay SS, Zamani M, Saturno D, et al. Risk of major adverse cardiovascular events in immune-mediated inflammatory disorders on biologics and small molecules: network meta-analysis. Clin Gastroenterol Hepatol, 2024, 22(5): 961-970.
23.	McHugh J. Cancer and cardiovascular risk with JAK inhibition. Nat Rev Rheumatol, 2023, 19(2): 64.
24.	Cohen SB. JAK inhibitors and VTE risk: how concerned should we be. Nat Rev Rheumatol, 2021, 17(3): 133-134.
25.	McInnes IB, Szekanecz Z, McGonagle D, et al. A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition. Rheumatology (Oxford), 2022, 61(5): 1783-1794.
26.	Li S, Li F, Mao N, et al. Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: a systematic review and meta-analysis. Eur J Intern Med, 2022, 102: 47-53.
27.	Lee YH, Song GG. Janus kinase inhibitors for treating active ankylosing spondylitis: a meta-analysis of randomized controlled trials. Z Rheumatol, 2022, 81(1): 71-76.

1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet, 2017, 390(10089): 73-84.
2. Navarro-Compán V, Sepriano A, El-Zorkany B, et al. Axial spondyloarthritis. Ann Rheum Dis, 2021, 80(12): 1511-1521.
3. Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis, 2009, 68(Suppl 2): 1-44.
4. López-Medina C, Moltó A. Update on the epidemiology, risk factors, and disease outcomes of axial spondyloarthritis. Best Pract Res Clin Rheumatol, 2018, 32(2): 241-253.
5. 吴珊珊, 段振华, 潘发明. 强直性脊柱炎流行病学研究进展. 安徽医科大学学报, 2013, 48(8): 988-992.
6. 黄烽, 朱剑, 王玉华, 等. 强直性脊柱炎诊疗规范. 中华内科杂志, 2022, 61(8): 893-900.
7. Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol, 2019, 71(10): 1599-1613.
8. Danve A, Deodhar A. Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol, 2022, 18(4): 205-216.
9. Lubrano E, De Socio A, Perrotta FM. Unmet needs in axial spondyloarthritis. Clin Rev Allergy Immunol, 2018, 55(3): 332-339.
10. Toussirot E. The use of Janus kinase inhibitors in axial spondyloarthritis: current insights. Pharmaceuticals (Basel), 2022, 15(3): 270.
11. 《Janus激酶抑制剂治疗风湿免疫病超药品说明书用药中国专家共识》制定专家组. Janus激酶抑制剂治疗风湿免疫病超药品说明书用药中国专家共识. 中华风湿病学杂志, 2023, 27(1): 1-9.
12. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum, 1984, 27(4): 361-368.
13. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis, 2009, 68(6): 777-783.
14. van der Heijde D, Deodhar A, Wei JC, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis, 2017, 76(8): 1340-1347.
15. Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis, 2021, 80(8): 1004-1013.
16. 姜克悦, 刘磊, 王文惠. 枸橼酸托法替布治疗活动性强直性脊柱炎的随机对照研究. 实用医学杂志, 2022, 38(11): 1415-1418.
17. van der Heijde D, Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet, 2019, 394(10214): 2108-2117.
18. van der Heijde D, Baraliakos X, Sieper J, et al. Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial. Ann Rheum Dis, 2022, 81(11): 1515-1523.
19. van der Heijde D, Baraliakos X, Gensler LS, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet, 2018, 392(10162): 2378-2387.
20. Deodhar A, Van den Bosch F, Poddubnyy D, et al. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2022, 400(10349): 369-379.
21. Winthrop KL, Cohen SB. Oral surveillance and JAK inhibitor safety: the theory of relativity. Nat Rev Rheumatol, 2022, 18(5): 301-304.
22. Mattay SS, Zamani M, Saturno D, et al. Risk of major adverse cardiovascular events in immune-mediated inflammatory disorders on biologics and small molecules: network meta-analysis. Clin Gastroenterol Hepatol, 2024, 22(5): 961-970.
23. McHugh J. Cancer and cardiovascular risk with JAK inhibition. Nat Rev Rheumatol, 2023, 19(2): 64.
24. Cohen SB. JAK inhibitors and VTE risk: how concerned should we be. Nat Rev Rheumatol, 2021, 17(3): 133-134.
25. McInnes IB, Szekanecz Z, McGonagle D, et al. A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition. Rheumatology (Oxford), 2022, 61(5): 1783-1794.
26. Li S, Li F, Mao N, et al. Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: a systematic review and meta-analysis. Eur J Intern Med, 2022, 102: 47-53.
27. Lee YH, Song GG. Janus kinase inhibitors for treating active ankylosing spondylitis: a meta-analysis of randomized controlled trials. Z Rheumatol, 2022, 81(1): 71-76.

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