WANG Jun, MENG Juan. Targeted Therapy for Rheumatoid Arthritis in the New Era[J]. Medical Journal of Peking Union Medical College Hospital, 2025, 16(1): 19-27. DOI: 10.12290/xhyxzz.2024-0842
Citation: WANG Jun, MENG Juan. Targeted Therapy for Rheumatoid Arthritis in the New Era[J]. Medical Journal of Peking Union Medical College Hospital, 2025, 16(1): 19-27. DOI: 10.12290/xhyxzz.2024-0842

Targeted Therapy for Rheumatoid Arthritis in the New Era

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  • Corresponding author:

    MENG Juan, E-mail: mserena@163.com

  • Received Date: October 26, 2024
  • Accepted Date: December 01, 2024
  • Issue Publish Date: January 29, 2025
  • Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. The clinical manifestation of RA involves various organs and systems both inside and outside the joints, and often exhibits strong clinical heterogeneity with unclear pathogenesis. Ineffective drug treatment for severe arthritis can result in physical disability and severely decreased quality of life. In recent years, targeted therapy for RA has become a hot research topic and has made new breakthroughs. Targeted treatments for RA mainly include two categories: biologic and targeted synthetic disease-modifying antirheumatic drugs. This article aims to elaborate on the current research status and progress of these drugs, with the hope of providing insights for clinicians to better guide personalized treatment for RA patients.

  • [1]
    Smolen J S, Aletaha D, McInnes I B. Rheumatoid arthritis[J]. Lancet, 2016, 388(10055): 2023-2038. DOI: 10.1016/S0140-6736(16)30173-8
    [2]
    Smith M H, Berman J R. What is rheumatoid arthritis?[J]. JAMA, 2022, 327(12): 1194. DOI: 10.1001/jama.2022.0786
    [3]
    Su Q Y, Luo J, Zhang Y, et al. Efficacy and safety of current therapies for difficult-to-treat rheumatoid arthritis: a systematic review and network meta-analysis[J]. J Transl Med, 2024, 22(1): 795. DOI: 10.1186/s12967-024-05569-x
    [4]
    Takeuchi T, Kawanishi M, Nakanishi M, et al. Phase Ⅱ/Ⅲ results of a trial of anti-tumor necrosis factor multivalent NANOBODY compound ozoralizumab in patients with rheumatoid arthritis[J]. Arthritis Rheumatol, 2022, 74(11): 1776-1785. DOI: 10.1002/art.42273
    [5]
    Jyssum I, Gehin J E, Sexton J, et al. Adalimumab serum levels and anti-drug antibodies: associations to treatment response and drug survival in inflammatory joint diseases[J]. Rheumatology (Oxford), 2024, 63(6): 1746-1755. DOI: 10.1093/rheumatology/kead525
    [6]
    Miyazaki Y, Nakayamada S, Tanaka H, et al. Comparison of anti-IL-6 receptor and JAK inhibitors in patients with rheumatoid arthritis from the real-world practice FIRST registry[J/OL]. Rheumatology (Oxford): keae334[2024-08-14]. https://doi.org/10.1093/rheumatology/keae334.
    [7]
    Nasonov E, Fatenejad S, Feist E, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inade-quately controlled by methotrexate: efficacy and safety results of a randomised controlled phase Ⅲ study[J]. Ann Rheum Dis, 2022, 81(4): 469-479. DOI: 10.1136/annrheumdis-2021-219876
    [8]
    Smolen J S, Feist E, Fatenejad S, et al. Olokizumab versus placebo or adalimumab in rheumatoid arthritis[J]. N Engl J Med, 2022, 387(8): 715-726. DOI: 10.1056/NEJMoa2201302
    [9]
    Brown P, Pratt A G, Hyrich K L. Therapeutic advances in rheumatoid arthritis[J]. BMJ, 2024, 384: e070856.
    [10]
    Ruscitti P, Berardicurti O, Cipriani P, et al. Benefits of anakinra versus TNF inhibitors in rheumatoid arthritis and type 2 diabetes: long-term findings from participants furtherly followed-up in the TRACK study, a multicentre, open-label, randomised, controlled trial[J]. Clin Exp Rheumatol, 2021, 39(2): 403-406. DOI: 10.55563/clinexprheumatol/phsqg7
    [11]
    Weinblatt M E, McInnes I B, Kremer J M, et al. A randomized phase Ⅱb study of mavrilimumab and golimumab in rheumatoid arthritis[J]. Arthritis Rheumatol, 2018, 70(1): 49-59. DOI: 10.1002/art.40323
    [12]
    Buckley C D, Simón-Campos J A, Zhdan V, et al. Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study[J]. Lancet Rheumatol, 2020, 2(11): e677-e688. DOI: 10.1016/S2665-9913(20)30229-0
    [13]
    Fleischmann R M, Van Der Heijde D, Strand V, et al. Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2)[J]. Ann Rheum Dis, 2023, 82(12): 1516-1526. DOI: 10.1136/ard-2023-224482
    [14]
    Taylor P C, Weinblatt M E, McInnes I B, et al. Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase Ⅲ randomised trial (contRAst 3)[J]. Ann Rheum Dis, 2023, 82(12): 1527-1537. DOI: 10.1136/ard-2023-224449
    [15]
    吴歆, 戚务芳, 王志强, 等. 风湿病靶向药物使用规范[J]. 中华内科杂志, 2022, 61(7): 756-763. DOI: 10.3760/cma.j.cn112138-20211220-00897

    Wu X, Qi W F, Wang Z Q, et al. Standardized management of targeted drugs for rheumatism[J]. Chin J Intern Med, 2022, 61(7): 756-763. DOI: 10.3760/cma.j.cn112138-20211220-00897
    [16]
    Rech J, Tascilar K, Hagen M, et al. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial[J]. Lancet, 2024, 403(10429): 850-859. DOI: 10.1016/S0140-6736(23)02650-8
    [17]
    Gerlag D M, Safy M, Maijer K I, et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study[J]. Ann Rheum Dis, 2019, 78(2): 179-185. DOI: 10.1136/annrheumdis-2017-212763
    [18]
    Rivellese F, Surace A E A, Goldmann K, et al. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial[J]. Nat Med, 2022, 28(6): 1256-1268. DOI: 10.1038/s41591-022-01789-0
    [19]
    Taylor P C, Quattrocchi E, Mallett S, et al. Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial[J]. Ann Rheum Dis, 2011, 70(12): 2119-2125. DOI: 10.1136/ard.2011.151522
    [20]
    Greenwald M, Szczepanski L, Kennedy A, et al. A 52-week, open-label study evaluating the safety and efficacy of tabalumab, an anti-B-cell-activating factor monoclonal antibody, for rheumatoid arthritis[J]. Arthritis Res Ther, 2014, 16(4): 415. DOI: 10.1186/s13075-014-0415-2
    [21]
    Genovese M C, Kinnman N, De La Bourdonnaye G, et al. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase Ⅱ, randomized, placebo-controlled, dose-finding trial[J]. Arthritis Rheum, 2011, 63(7): 1793-1803. DOI: 10.1002/art.30373
    [22]
    Wang L, Xu D, Fang J M, et al. Telitacicept, a human recombinant fusion protein targeting and neutralizing B Lymphocyte Stimulator (BlyS) and a proliferation-inducing ligand (APRIL), in rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX): a randomized, double-blind, phase 3 study[J]. Arthritis Rheumatol, 2023, 75(S9): L20.
    [23]
    Karnell J L, Albulescu M, Drabic S, et al. A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity[J]. Sci Transl Med, 2019, 11(489): eaar6584. DOI: 10.1126/scitranslmed.aar6584
    [24]
    Bucci L, Hagen M, Rothe T, et al. Bispecific T cell engager therapy for refractory rheumatoid arthritis[J]. Nat Med, 2024, 30(6): 1593-1601. DOI: 10.1038/s41591-024-02964-1
    [25]
    Tuttle J, Drescher E, Simón-Campos J A, et al. A phase 2 trial of peresolimab for adults with rheumatoid arthritis[J]. N Engl J Med, 2023, 388(20): 1853-1862. DOI: 10.1056/NEJMoa2209856
    [26]
    Rosenberg S A, Restifo N P. Adoptive cell transfer as personalized immunotherapy for human cancer[J]. Science, 2015, 348(6230): 62-68. DOI: 10.1126/science.aaa4967
    [27]
    Jacoby E, Shahani S A, Shah N N. Updates on CAR T-cell therapy in B-cell malignancies[J]. Immunol Rev, 2019, 290(1): 39-59. DOI: 10.1111/imr.12774
    [28]
    Zhang B, Wang Y, Yuan Y S, et al. In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells[J]. Ann Rheum Dis, 2021, 80(2): 176-184. DOI: 10.1136/annrheumdis-2020-217844
    [29]
    Caporali R, Taylor P C, Aletaha D, et al. Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis up to 6.5 years of treatment: results of a long-term study[J]. Rheumatology (Oxford), 2024, 63(10): 2799-2809. DOI: 10.1093/rheumatology/keae012
    [30]
    Tanaka Y, Kishimoto M, Sonomoto K, et al. Methotrexate, tofacitinib, and biologic disease-modifying antirheumatic drug safety and effectiveness among patients with rheumatoid arthritis in Japan: CorEvitas registry observational study[J]. Rheumatol Ther, 2024, 11(5): 1237-1253. DOI: 10.1007/s40744-024-00700-2
    [31]
    Zarrin A A, Bao K, Lupardus P, et al. Kinase inhibition in autoimmunity and inflammation[J]. Nat Rev Drug Discov, 2021, 20(1): 39-63. DOI: 10.1038/s41573-020-0082-8
    [32]
    Tang Q, Fakih H H, Zain UI Abideen M, et al. Rational design of a JAK1-selective siRNA inhibitor for the modula-tion of autoimmunity in the skin[J]. Nat Commun, 2023, 14(1): 7099. DOI: 10.1038/s41467-023-42714-4
    [33]
    Tavakoli G M, Yazdanpanah N, Rezaei N. Targeting Bruton's tyrosine kinase (BTK) as a signaling pathway in immune-mediated diseases: from molecular mechanisms to leading treatments[J]. Adv Rheumatol, 2024, 64(1): 61. DOI: 10.1186/s42358-024-00401-y
    [34]
    Taylor P C, Genovese M C, Greenwood M, et al. OSKIRA-4: a phase Ⅱb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy[J]. Ann Rheum Dis, 2015, 74(12): 2123-2129. DOI: 10.1136/annrheumdis-2014-205361
    [35]
    Crocetti L, Floresta G, Cilibrizzi A, et al. An overview of PDE4 inhibitors in clinical trials: 2010 to early 2022[J]. Molecules, 2022, 27(15): 4964. DOI: 10.3390/molecules27154964
    [36]
    Huss V, Bower H, Wadström H, et al. Short- and longer-term cancer risks with biologic and targeted synthetic disease-modifying antirheumatic drugs as used against rheumatoid arthritis in clinical practice[J]. Rheumatology (Oxford), 2022, 61(5): 1810-1818. DOI: 10.1093/rheumatology/keab570
    [37]
    Westermann R, Cordtz R L, Duch K, et al. Cancer risk with tocilizumab/sarilumab, abatacept, and rituximab treatment in patients with rheumatoid arthritis: a Danish cohort study[J/OL]. Rheumatology (Oxford): keae140[2024-09-04]. https://doi.org/10.1093/rheumatology/keae140.
    [38]
    Huss V, Bower H, Hellgren K, et al. Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study[J]. Ann Rheum Dis, 2023, 82(7): 911-919. DOI: 10.1136/ard-2022-223636
    [39]
    Luciano N, Barone E, Timilsina S, et al. Tumor necrosis factor alpha inhibitors and cardiovascular risk in rheumatoid arthritis[J]. Clin Rev Allergy Immunol, 2023, 65(3): 403-419. DOI: 10.1007/s12016-023-08975-z
    [40]
    Aymon R, Mongin D, Bergstra S A, et al. Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study)[J]. Ann Rheum Dis, 2024, 83(4): 421-428. DOI: 10.1136/ard-2023-224670
    [41]
    Khosrow-Khavar F, Kim S C, Lee H, et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study[J]. Ann Rheum Dis, 2022, 81(6): 798-804. DOI: 10.1136/annrheumdis-2021-221915
    [42]
    Popa C D, Opdam M A A, Den Broeder N, et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population[J]. Rheumatology (Oxford), 2024, 63(8): 2142-2146. DOI: 10.1093/rheumatology/kead531
    [43]
    Pappas D A, Reed G, Kane K, et al. Effect of biologic agents and inflammation on lipid levels and cardiovascular risk in rheumatoid arthritis patients[J]. Semin Arthritis Rheum, 2024, 68: 152504. DOI: 10.1016/j.semarthrit.2024.152504
    [44]
    Frisell T, Bower H, Morin M, et al. Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme[J]. Ann Rheum Dis, 2023, 82(5): 601-610. DOI: 10.1136/ard-2022-223762
    [45]
    Opdam M A A, Broeder N D, Van Den Bemt B J F, et al. Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs[J]. Clin Rheumatol, 2024, 43(6): 2133-2138. DOI: 10.1007/s10067-024-06980-x
    [46]
    Venerito V, Stefanizzi P, Cantarini L, et al. Immunogenicity and safety of adjuvanted recombinant zoster vaccine in rheumatoid arthritis patients on anti-cellular biologic agents or JAK inhibitors: a prospective observational study[J]. Int J Mol Sci, 2023, 24(8): 6967. DOI: 10.3390/ijms24086967
    [47]
    Kuo M H, Tseng C W, Ko P H, et al. HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs[J]. Liver Int, 2024, 44(2): 497-507. DOI: 10.1111/liv.15793
    [48]
    Mahajan T D, Hooker R, Maher L, et al. Abatacept therapy for rheumatoid arthritis in the setting of hepatitis C infection[J]. J Clin Rheumatol, 2010, 16(7): 332-334. DOI: 10.1097/RHU.0b013e3181f4cd92
    [49]
    Liao T L, Chen I C, Chen H W, et al. Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C[J]. Sci Rep, 2024, 14(1): 937. DOI: 10.1038/s41598-023-50963-y
    [50]
    Yoshimura Y, Yamanouchi M, Mizuno H, et al. Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease[J]. Ann Rheum Dis, 2024, 83(10): 1278-1287. DOI: 10.1136/ard-2024-225914
    [51]
    Nader A, Stodtmann S, Friedel A, et al. Pharmaco-kinetics of upadacitinib in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis: population analyses of phase 1 and 2 clinical trials[J]. J Clin Pharmacol, 2020, 60(4): 528-539. DOI: 10.1002/jcph.1550
    [52]
    Tardella M, Di Carlo M, Carotti M, et al. A retrospective study of the efficacy of JAK inhibitors or abatacept on rheumatoid arthritis-interstitial lung disease[J]. Inflammopharmacology, 2022, 30(3): 705-712. DOI: 10.1007/s10787-022-00936-w

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