REFERENCES
1. Tian J, Zhang D, Yao X, Huang Y, Lu Q. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023;82:351-6.
2. Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382:211-21.
3. Moulton VR, Suarez-Fueyo A, Meidan E, Li H, Mizui M, Tsokos GC. Pathogenesis of human systemic lupus erythematosus: a cellular perspective. Trends Mol Med. 2017;23:615-35.
4. Crow MK. Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets. Ann Rheum Dis. 2023;82:999-1014.
5. Dubey AK, Handu SS, Dubey S, Sharma P, Sharma KK, Ahmed QM. Belimumab: first targeted biological treatment for systemic lupus erythematosus. J Pharmacol Pharmacother. 2011;2:317-9.
6. Thomson RJ, Moshirfar M, Ronquillo Y. Tyrosine kinase inhibitors. StatPearls. Treasure Island (FL) Ineligible Companies, 2024. Available from: https://clinicaltrials.gov/study/NCT03288324 [Last accessed on 19 Jan 2026].
7. Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6:402.
8. Cleary JM, Shapiro GI. Development of phosphoinositide-3 kinase pathway inhibitors for advanced cancer. Curr Oncol Rep. 2010;12:87-94.
9. Favalli EG, Maioli G, Caporali R. Biologics or janus kinase inhibitors in rheumatoid arthritis patients who are insufficient responders to conventional anti-rheumatic drugs. Drugs. 2024;84:877-94.
10. Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nat Rev Rheumatol. 2022;18:133-45.
11. Alunno A, Padjen I, Fanouriakis A, Boumpas DT. Pathogenic and therapeutic relevance of JAK/STAT signaling in systemic lupus erythematosus: integration of distinct inflammatory pathways and the prospect of their inhibition with an oral agent. Cells. 2019;8:898.
12. Jamilloux Y, El Jammal T, Vuitton L, Gerfaud-Valentin M, Kerever S, Sève P. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2019;18:102390.
13. Xue C, Yao Q, Gu X, et al. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduct Target Ther. 2023;8:204.
14. Ripoll È, de Ramon L, Draibe Bordignon J, et al. JAK3-STAT pathway blocking benefits in experimental lupus nephritis. Arthritis Res Ther. 2016;18:134.
15. Lu LD, Stump KL, Wallace NH, et al. Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2. J Immunol. 2011;187:3840-53.
16. Twomey RE, Perper SJ, Westmoreland SV, et al. Therapeutic JAK1 inhibition reverses lupus nephritis in a mouse model and demonstrates transcriptional changes consistent with human disease. ACR Open Rheumatol. 2024;6:900-11.
17. Dong G, You M, Fan H, Ding L, Sun L, Hou Y. STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells. Eur J Immunol. 2015;45:2377-88.
18. Furumoto Y, Smith CK, Blanco L, et al. Tofacitinib ameliorates murine lupus and its associated vascular dysfunction. Arthritis Rheumatol. 2017;69:148-60.
19. Li X, Luo K, Yang D, Hou C. A case report of systemic lupus erythematosus complicating interstitial lung disease and thickened pericardium treated with tofacitinib. Medicine. 2024;103:e39129.
20. Chen YL, Liu LX, Huang Q, Li XY, Hong XP, Liu DZ. Case report: reversal of long-standing refractory diffuse non-scarring alopecia due to systemic lupus erythematosus following treatment with tofacitinib. Front Immunol. 2021;12:654376.
21. Hasni SA, Gupta S, Davis M, et al. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021;12:3391.
22. Alsukait S, Learned C, Rosmarin D. Open-label phase 2 pilot study of oral tofacitinib in adult subjects with discoid lupus erythematosus (DLE). J Drugs Dermatol. 2023;22:425-7.
23. Clinicaltrials.gov. Open-label study of tofacitinib for moderate to severe skin involvement in young adults with lupus. 2024. Available from: https://clinicaltrials.gov/study/NCT03288324 [Last accessed on 28 Nov 2025].
24. Nakayamada S, Tanaka Y. Novel JAK inhibitors under investigation for systemic lupus erythematosus: - where are we now? Expert Opin Investig Drugs. 2023;32:901-8.
25. Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392:222-31.
26. Dörner T, Tanaka Y, Petri MA, et al. Baricitinib-associated changes in global gene expression during a 24-week phase II clinical systemic lupus erythematosus trial implicates a mechanism of action through multiple immune-related pathways. Lupus Sci Med. 2020;7:e000424.
27. Morand EF, Vital EM, Petri M, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). Lancet. 2023;401:1001-10.
28. Petri M, Bruce IN, Dörner T, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). Lancet. 2023;401:1011-9.
29. Yin J, Hou Y, Wang C, Qin C. Clinical outcomes of baricitinib in patients with systemic lupus erythematosus: Pooled analysis of SLE-BRAVE-I and SLE-BRAVE-II trials. PLoS One. 2025;20:e0320179.
30. Connelly K, Golder V, Kandane-Rathnayake R, Morand EF. Clinician-reported outcome measures in lupus trials: a problem worth solving. Lancet Rheumatol. 2021;3:e595-603.
31. Askanase AD, Vital EM, Meier O, et al. Evaluating the concordance between BICLA and SRI4 in patients with systemic lupus erythematosus from the placebo arms of the EXPLORER and ATHOS trials. Lupus Sci Med. 2025;12:e001483.
32. Clinicaltrials.gov. A dose-ranging study to evaluate efficacy and safety of PF-06700841 in systemic lupus erythematosus (SLE). 2024. Available from: https://clinicaltrials.gov/study/NCT03845517 [Last accessed on 28 Nov 2025].
33. Morand E, Pike M, Merrill JT, et al. Deucravacitinib, a tyrosine kinase 2 inhibitor, in systemic lupus erythematosus: a phase II, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2023;75:242-52.
34. Werth VP, Fleischmann R, Robern M, et al. Filgotinib or lanraplenib in moderate to severe cutaneous lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled study. Rheumatology. 2022;61:2413-23.
35. Baker M, Chaichian Y, Genovese M, et al. Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD Open. 2020;6:e001490.
36. Merrill JT, Tanaka Y, D'Cruz D, et al. Efficacy and safety of upadacitinib or elsubrutinib alone or in combination for patients with systemic lupus erythematosus: a phase 2 randomized controlled trial. Arthritis Rheumatol. 2024;76:1518-29.
37. Kahl L, Patel J, Layton M, et al. Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. Lupus. 2016;25:1420-30.
38. Chan ES, Herlitz LC, Ali J. Ruxolitinib attenuates cutaneous lupus development in a mouse lupus model. J Invest Dermatol. 2015;135:2338-9.
39. Klaeschen AS, Wolf D, Brossart P, Bieber T, Wenzel J. JAK inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus. Exp Dermatol. 2017;26:728-30.
40. Park JJ, Little AJ, Vesely MD. Treatment of cutaneous lupus with topical ruxolitinib cream. JAAD Case Rep. 2022;28:133-5.
41. Jung JI, Kim JY, Kim MH, et al. Successful treatment of hemophagocytic lymphohistiocytosis in a patient with systemic lupus erythematosus with ruxolitinib: a case report. J Rheum Dis. 2024;31:125-9.
42. Ringheim GE, Wampole M, Oberoi K. Bruton's tyrosine kinase (BTK) inhibitors and autoimmune diseases: making sense of BTK inhibitor specificity profiles and recent clinical trial successes and failures. Front Immunol. 2021;12:662223.
43. Ding Q, Zhou Y, Feng Y, Sun L, Zhang T. Bruton's tyrosine kinase: a promising target for treating systemic lupus erythematosus. Int Immunopharmacol. 2024;142:113040.
44. Wallace DJ, Dörner T, Pisetsky DS, et al. Efficacy and safety of the bruton's tyrosine kinase inhibitor evobrutinib in systemic lupus erythematosus: results of a phase II, randomized, double-blind, placebo-controlled dose-ranging trial. ACR Open Rheumatol. 2023;5:38-48.
45. Tanaka Y, Nakayamada S, Yamaoka K, Ohmura K, Yasuda S. Rituximab in the real-world treatment of lupus nephritis: a retrospective cohort study in Japan. Mod Rheumatol. 2023;33:145-53.
46. Liao HT, Tung HY, Tsai CY, Chiang BL, Yu CL. Bruton's tyrosine kinase in systemic lupus erythematosus. Joint Bone Spine. 2020;87:670-2.
47. Kim YY, Park KT, Jang SY, et al. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017;19:211.
48. Li R, Zhu X, Liu S, Zhang X, Xie C, Fu Z, et al. LB0005 orelabrutinib, an irreversible inhibitor of bruton's tyrosine kinase (BTK), for the treatment of systemic lupus erythematosus (SLE): results of a randomized, double-blinder, placebo-controlled, phase IB/IIA dose-finding study. Ann Rheum Dis. 2022;81:210.
49. Isenberg D, Furie R, Jones NS, et al. Efficacy, safety, and pharmacodynamic effects of the bruton's tyrosine kinase inhibitor fenebrutinib (GDC-0853) in systemic lupus erythematosus: results of a phase II, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2021;73:1835-46.
50. Mina-Osorio P, LaStant J, Keirstead N, et al. Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum. 2013;65:2380-91.
51. Chalmers SA, Wen J, Doerner J, et al. Highly selective inhibition of Bruton's tyrosine kinase attenuates skin and brain disease in murine lupus. Arthritis Res Ther. 2018;20:10.
52. Weißenberg SY, Szelinski F, Schrezenmeier E, et al. Identification and characterization of post-activated B cells in systemic autoimmune diseases. Front Immunol. 2019;10:2136.
53. Mok CC. Targeted small molecules for systemic lupus erythematosus: drugs in the pipeline. Drugs. 2023;83:479-96.
54. Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 2010;10:387-402.
55. Cooper N, Ghanima W, Hill QA, Nicolson PL, Markovtsov V, Kessler C. Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib. Platelets. 2023;34:2131751.
56. Grammatikos AP, Ghosh D, Devlin A, Kyttaris VC, Tsokos GC. Spleen tyrosine kinase (Syk) regulates systemic lupus erythematosus (SLE) T cell signaling. PLoS One. 2013;8:e74550.
57. Pohlmeyer CW, Shang C, Han P, et al. Characterization of the mechanism of action of lanraplenib, a novel spleen tyrosine kinase inhibitor, in models of lupus nephritis. BMC Rheumatol. 2021;5:15.
58. Tanaka Y, Millson D, Iwata S, Nakayamada S. Safety and efficacy of fostamatinib in rheumatoid arthritis patients with an inadequate response to methotrexate in phase II OSKIRA-ASIA-1 and OSKIRA-ASIA-1X study. Rheumatology. 2021;60:2884-95.
59. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93:921-30.
60. Deng GM, Liu L, Bahjat FR, Pine PR, Tsokos GC. Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis Rheum. 2010;62:2086-92.
61. Cho S, Jang E, Yoon T, Hwang H, Youn J. A novel selective spleen tyrosine kinase inhibitor SKI-O-703 (cevidoplenib) ameliorates lupus nephritis and serum-induced arthritis in murine models. Clin Exp Immunol. 2023;211:31-45.
62. Sunder S, Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Signal Transduct Target Ther. 2023;8:262.
63. Rambhatla A, Strug MR, De Paredes JG, Cordoba Munoz MI, Thakur M. Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: a review. J Assist Reprod Genet. 2021;38:1897-908.
64. Rosario R, Cui W, Anderson RA. Potential ovarian toxicity and infertility risk following targeted anti-cancer therapies. Reprod Fertil. 2022;3:R147-62.
65. Dou X, Qin Y, Huang X, Jiang Q. Planned pregnancy in female patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. Oncologist. 2019;24:e1141-7.
66. Hoisnard L, Pina Vegas L, Dray-Spira R, Weill A, Zureik M, Sbidian E. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study. Ann Rheum Dis. 2023;82:182-8.
67. Ytterberg SR, Bhatt DL, Connell CA. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:1766-8.
68. Adas MA, Alveyn E, Cook E, Dey M, Galloway JB, Bechman K. The infection risks of JAK inhibition. Expert Rev Clin Immunol. 2022;18:253-61.
69. Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018;77:355-63.
70. Bass AR, Chakravarty E, Akl EA, et al. 2022 American college of rheumatology guideline for vaccinations in patients with rheumatic and musculoskeletal diseases. Arthritis Care Res. 2023;75:449-64.
71. Awan FT, Addison D, Alfraih F, et al. International consensus statement on the management of cardiovascular risk of Bruton's tyrosine kinase inhibitors in CLL. Blood Adv. 2022;6:5516-25.
72. Weinblatt ME, Kavanaugh A, Genovese MC, Musser TK, Grossbard EB, Magilavy DB. An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med. 2010;363:1303-12.
73. He Y, Sun MM, Zhang GG, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021;6:425.
74. Hawkins PT, Stephens LR. PI3K signalling in inflammation. Biochim Biophys Acta. 2015;1851:882-97.
75. Omori SA, Cato MH, Anzelon-Mills A, et al. Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity. 2006;25:545-57.
76. Bacalao MA, Satterthwaite AB. Recent advances in lupus B cell biology: PI3K, IFNγ, and chromatin. Front Immunol. 2020;11:615673.
77. O'Neill SK, Getahun A, Gauld SB, et al. Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy. Immunity. 2011;35:746-56.
78. Wu XN, Ye YX, Niu JW, et al. Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus. Sci Transl Med. 2014;6:246ra99.
79. Olayinka-Adefemi F, Hou S, Marshall AJ. Dual inhibition of phosphoinositide 3-kinases delta and gamma reduces chronic B cell activation and autoantibody production in a mouse model of lupus. Front Immunol. 2023;14:1115244.
80. Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008-18.
81. Gribben JG, Jurczak W, Jacobs RW, et al. Umbralisib plus ublituximab (U2) Is superior to obinutuzumab plus chlorambucil (O+Chl) in patients with treatment naïve (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): results from the phase 3 Unity-CLL study. Blood. 2020;136:37-9.
82. Lui SL, Tsang R, Chan KW, et al. Rapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 mice. Nephrol Dial Transplant. 2008;23:2768-76.
83. Yap DY, Ma MK, Tang CS, Chan TM. Proliferation signal inhibitors in the treatment of lupus nephritis: preliminary experience. Nephrology. 2012;17:676-80.
84. Lai ZW, Kelly R, Winans T, et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet. 2018;391:1186-96.
85. Michailidou D, Gartshteyn Y, Askanase AD, Perl A. The role of mTOR signaling pathway in systemic lupus erythematosus and systemic vasculitis. Autoimmun Rev. 2025;24:103910.
86. Brightbill HD, Suto E, Blaquiere N, et al. NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus. Nat Commun. 2018;9:179.
