Skip to main content

Advertisement

SpringerLink
Log in

Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets.

Methods

An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry.

Results

Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline.

Conclusion

Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings.

Key Points

• Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging.

• This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM.

• Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Allenbach Y, Uzunhan Y, Toquet S, Leroux G, Gallay L, Marquet A et al (2020) Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases. Neurology 95(1):e70–e78. https://doi.org/10.1212/WNL.0000000000009727

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nombel A, Fabien N, Coutant F (2021) Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features Pathogenesis and Emerging Therapies. Front Immunol 12:773352. https://doi.org/10.3389/fimmu.2021.773352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H et al (2020) Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis. Arthritis Rheumatol 72(3):488–498. https://doi.org/10.1002/art.41105

    Article  CAS  PubMed  Google Scholar 

  4. Nakashima R, Hosono Y, Mimori T (2016) Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus 25:925–933. https://doi.org/10.1177/0961203316651748

    Article  CAS  PubMed  Google Scholar 

  5. Gono T, Miyake K, Kawaguchi Y, Kaneko H, Shinozaki M, Yamanaka H (2012) Hyperferritinaemia and macrophage activation in a patient with interstitial lung disease with clinically amyopathic dermatomyositis. Rheumatology 51(7):1336–1338. https://doi.org/10.1093/rheumatology/kes012

    Article  PubMed  Google Scholar 

  6. Gono T, Kaneko H, Kawaguchi Y, Hanaoka M, Kataoka S, Kuwana M et al (2014) Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology 53(12):2196–2203. https://doi.org/10.1093/rheumatology/keu258

    Article  CAS  PubMed  Google Scholar 

  7. Zhang SH, Zhao Y, Xie QB, Jiang Y, Wu YK, Yan B (2019) Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis. Br J Dermatol 180(5):1090–1098. https://doi.org/10.1111/bjd.16917

    Article  CAS  PubMed  Google Scholar 

  8. Hornung T, Janzen V, Heidgen FJ, Wolf D, Bieber T, Wenzel J et al (2014) Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 371(26):2537–2538. https://doi.org/10.1056/NEJMc1412997

    Article  PubMed  Google Scholar 

  9. Kurasawa K, Arai S, Namiki Y, Tanaka A, Takamura Y, Owada T et al (2018) Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford) 57(12):2114–2119. https://doi.org/10.1093/rheumatology/key188

    Article  CAS  PubMed  Google Scholar 

  10. Chen Z, Wang X, Ye S (2019) Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. N Engl J Med 381(3):291–293. https://doi.org/10.1056/NEJMc1900045

    Article  PubMed  Google Scholar 

  11. Hodge JA, Kawabata TT, Krishnaswami S, Krishnaswami S, Clark JD, Telliez JB, Dowty ME et al (2016) The mechanism of action of tofacitinib: an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol 34(2):318–328

  12. Strober B, Buonanno M, Clark JD, Kawabata T, Tan H, Wolk R et al (2013) Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters during 12 weeks of psoriasis treatment. Br J Dermatol 169(5):992–999. https://doi.org/10.1111/bjd.12517

    Article  CAS  PubMed  Google Scholar 

  13. Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M et al (2017) 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 76:1955–1964. https://doi.org/10.1136/annrheumdis-2017-211468

    Article  PubMed  Google Scholar 

  14. Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE et al (2004) International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 43(1):49–54. https://doi.org/10.1093/rheumatology

    Article  CAS  PubMed  Google Scholar 

  15. He L, Shu XM, Liu X, Ge YP, Li SZ, Lu X et al (2020) Soluble IL-2 receptor in dermatomyositis: its associations with skin ulcers and disease activity. Mediators Inflamm 2020:6243019. https://doi.org/10.1155/2020/6243019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aggarwal R, Rider LG, Ruperto N, Bayat N, Erman B, Feldman BM et al (2017) 2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: an International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis 76:792–801. https://doi.org/10.1136/annrheumdis-2017-211400

    Article  PubMed  Google Scholar 

  17. Takatani A, Koga T, Fujita Y, Fukui S, Endo Y, Shimizu T et al (2020) Efficacy of tofacitinib for slowly progressive interstitial lung disease in a patient with anti-MDA5 antibody-positive dermatomyositis. Clin Immunol 215:108451. https://doi.org/10.1016/j.clim.2020.108451

    Article  CAS  PubMed  Google Scholar 

  18. Ishikawa Y, Kasuya T, Fujiwara M, Kita Y et al (2020) Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission: a case report. Medicine 99:e21943. https://doi.org/10.1097/MD.0000000000021943

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hosokawa Y, Oiwa H (2021) A Case of Refractory Interstitial Lung Disease in Anti-MDA5-Positive Dermatomyositis That Improved After Switching to Tofacitinib. J Clin Rheumatol 27:S661–S662. https://doi.org/10.1097/RHU.0000000000001645

    Article  PubMed  Google Scholar 

  20. Ohmura SI, Yamabe T, Naniwa T (2021) Successful dose escalation of tofacitinib for refractory dermatomyositis and interstitial lung disease with anti-melanoma differentiation-associated gene 5 antibodies. Mod Rheumatol Case Rep 5:76–81. https://doi.org/10.1080/24725625.2020.1816674

    Article  PubMed  Google Scholar 

  21. Kato M, Ikeda K, Kageyama T, Kasuya T, Kumagai T, Furuya H et al (2019) Successful Treatment for Refractory Interstitial Lung Disease and Pneumomediastinum With Multidisciplinary Therapy Including Tofacitinib in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis. J Clin Rheumatol 27:S574–S577. https://doi.org/10.1097/RHU.0000000000000984

    Article  Google Scholar 

  22. Takanashi S, Kaneko Y, Takeuchi T (2021) Tofacitinib in interstitial lung disease complicated with anti-MDA5 antibody-positive dermatomyositis: A literature review. Mod Rheumatol 15:1–7. https://doi.org/10.1080/14397595.2021.1906505

    Article  CAS  Google Scholar 

  23. Wendel S, Venhoff N, Frye BC, May AM, Agarwal P, Rizzi M et al (2019) Successful treatment of extensive calcifications and acute pulmonary involvement in dermatomyositis with the Janus-Kinase inhibitor tofacitinib - A report of two cases. J Autoimmun 100:131–136. https://doi.org/10.1016/j.jaut.2019.03.003

    Article  CAS  PubMed  Google Scholar 

  24. Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y et al (2012) Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology 51(9):1563–1570. https://doi.org/10.1093/rheumatology/kes102

    Article  CAS  PubMed  Google Scholar 

  25. Fujiki Y, Kotani T, Isoda K, Ishida T, Shoda T, Yoshida S et al (2018) Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients. Mod Rheumatol 28:133–140. https://doi.org/10.1080/14397595.2017.1318468

    Article  CAS  PubMed  Google Scholar 

  26. Chen F, Wang DX, Shu XM, Nakashima R, Wang GC (2012) Anti-MDA5 antibody is associated with A/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis. Rheumatol Int 32(12):3909–3915. https://doi.org/10.1007/s00296-011-2323-y

    Article  CAS  PubMed  Google Scholar 

  27. Ye Y, Chen Z, Jiang S, Jia F, Li T, Lu X et al (2022) Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13(1):6458. https://doi.org/10.1038/s41467-022-34145-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ye Y, Zhang X, Li T, Ma J, Wang R, Wu C, Wang R et al (2022) Two Distinct Immune Cell Signatures Predict the Clinical Outcomes in Patients With Amyopathic Dermatomyositis With Interstitial Lung Disease. Arthritis Rheumatol 74(11):1822–1832. https://doi.org/10.1002/art.42264

    Article  CAS  PubMed  Google Scholar 

  29. Weinhold KJ, Bukowski JF, Brennan TV, Noveck RJ, Staats JS, Lin L et al (2018) Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers. Clin Immunol 191:10–20. https://doi.org/10.1016/j.clim.2018.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. van Vollenhoven R, Lee EB, Strengholt S, Mojcik C, Valdez H, Krishnaswami S et al (2019) Evaluation of the Short- , Mid- , and Long- Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis. Arthritis Rheumatol 71:685–695. https://doi.org/10.1002/art.40780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huang W, Ren F, Luo L, Zhou J, Huang D, Pan Z et al (2020) The characteristics of lymphocytes in patients positive for anti-MDA5 antibodies in interstitial lung disease. Rheumatology (Oxford) 59:3886–3891. https://doi.org/10.1093/rheumatology/keaa266

    Article  CAS  PubMed  Google Scholar 

  32. Gui X, Shenyun S, Ding H, Wang R, Tong J, Yu M et al (2022) Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease. Rheumatology (Oxford) 61(11):4570–4578. https://doi.org/10.1093/rheumatology/keac090

    Article  CAS  PubMed  Google Scholar 

  33. Lv C, You H, Xu L, Wang L, Yuan F, Li J et al (2022) Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody-Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk. J Rheumatol 50(2):219–226. https://doi.org/10.3899/jrheum.220139

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We extended our thanks to all the patients and participating investigators.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Yanhua Wang, Jing Luo, Xiaohong Lv, Yuanyuan Li, Qi An, Lingfei Mo, Nan Hu, Jing Zhang, Jing Wang, Juan Tian, Dan Pu, Zhiming Hao & Lan He

Authors
  1. Yanhua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohong Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuanyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qi An
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lingfei Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Juan Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dan Pu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zhiming Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lan He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lan He.

Ethics declarations

Disclosures

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yanhua Wang is the first author.

Jing Luo is the Co-first author.

Supplementary information

Supplementary Table 2

Myositis response criteria using change in core set measures for patients. (DOCX 19 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Luo, J., Lv, X. et al. Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis. Clin Rheumatol 42, 1847–1853 (2023). https://doi.org/10.1007/s10067-023-06567-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-023-06567-y

Keywords

Search

Navigation