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The Chinese herb Tripterygium wilfordii Hook F for the treatment of systemic sclerosis-associated interstitial lung disease: data from a Chinese EUSTAR Center

  • Luwei Yang
  • Qian Wang
  • Yong Hou
  • Jiuliang Zhao
  • Mengtao Li
  • Dong XuEmail author
  • Xiaofeng ZengEmail author
Original Article
  • 51 Downloads

Abstract

Objective

To assess the efficacy and safety of the Chinese herb Tripterygium wilfordii Hook F (TwHF) for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods

SSc-ILD patients who were regularly treated for more than 1 year and were currently taking a stable dose of TwHF (40–60 mg/day) or CYC (100 mg/day) were selected from the EUSTAR database of Peking Union Medical College Hospital. The efficacy of treatments was assessed by the change in pulmonary function, including the forced vital capacity (FVC) and the percentage of predicted FVC (FVC pred%).

Results

Among the 431 patients diagnosed with SSc-ILD, 76 fulfilled the inclusion and exclusion criteria. Twenty eight patients received TwHF monotherapy, while 48 received oral CYC monotherapy. Baseline data prior to treatment did not differ significantly between the two groups. After 1 year of treatment, significant improvements in the FVC and FVC pred% were seen in both groups (P < 0.05) and the magnitude of improvement was comparable (P = 0.93). However, TwHF was only found to be effective in improving FVC and FVC pred% when administered as a maintenance therapy, but not as an induction therapy. No severe adverse events were seen in either group. Leucopenia occurred more often in the CYC group compared to the TwHF group (P = 0.034).

Conclusion

TwHF may be considered as a potential alternative drug for SSc-ILD patients, especially as a maintenance therapy. A prospective randomized controlled trial is necessary to further confirm these results.

Key Points

• This is the first clinical study of Tripterygium wilfordii Hook F (TwHF) in the treatment of SSc-ILD, providing a novel therapeutic option for SSc-ILD.

• TwHF shows a comparable therapeutic efficacy to CYC when treating SSc-ILD.

• TwHF has unique therapeutic advantages considering the balance of economy and safety and may be a good potential choice for maintenance therapy.

Keywords

Cyclophosphamide Interstitial lung disease Systemic sclerosis Tripterygium wilfordii Hook F 

Notes

Financial support

This work was supported by the National Key Research and Development Program of China (grant no. 2016YFC0901500); Center for Rare Diseases Research, Chinese Academy of Medical Sciences, Beijing, China (grant no. 2016ZX310174-4); and a grant from CAMS Innovation Fund for Medical Sciences (CIFMS; no. 2016-I2M-1-002).

Compliance with ethical standards

The study protocol was approved by the Medical Ethics Committee of PUMCH (Beijing, China). Informed consent was not relevant as it was a retrospective study.

Disclosures

None.

References

  1. 1.
    Xu D, Li MT, Hou Y et al (2011) Preliminary analysis of Chinese patients with systemic sclerosis. Chin J Rheumatol 7:455–459Google Scholar
  2. 2.
    Giacomelli R, Liakouli V, Berardicurti O et al (2017) Interstitial lung disease in systemic sclerosis: current and future treatment. Rheumatol Int 37(6):853–863PubMedCrossRefGoogle Scholar
  3. 3.
    Dimitroulas T, Giannakoulas G, Karvounis H, Settas L, Kitas GD (2012) Systemic sclerosis-related pulmonary hypertension: unique characteristics and future treatment targets. Curr Pharm Des 18(11):1457–1464PubMedCrossRefGoogle Scholar
  4. 4.
    Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 66(7):940–944PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Tashkin DP, Roth MD, Clements PJ et al (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4(9):708–719PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Poormoghim H, Moradi Lakeh M, Mohammadipour M, Sodagari F, Toofaninjed N (2012) Cyclophosphamide for scleroderma lung disease: a systematic review and meta-analysis. Rheumatol Int 32(8):2431–2444PubMedCrossRefGoogle Scholar
  7. 7.
    Walker UA, Tyndall A, Czirjak L et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 66(6):754–763PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Ferri C, Valentini G, Cozzi F et al (2002) Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 81(2):139–153CrossRefGoogle Scholar
  9. 9.
    Tashkin DP, Elashoff R, Clements PJ et al (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354(25):2655–2666PubMedCrossRefGoogle Scholar
  10. 10.
    Furst DE, Tseng CH, Clements PJ et al (2011) Adverse events during the Scleroderma Lung Study. Am J Med 124(5):459–467PubMedCrossRefGoogle Scholar
  11. 11.
    Martinez FJ, McCune WJ (2006) Cyclophosphamide for scleroderma lung disease. N Engl J Med 354(25):2707–2709PubMedCrossRefGoogle Scholar
  12. 12.
    Lv QW, Zhang W, Shi Q et al (2015) Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial. Ann Rheum Dis 74(6):1078–1086PubMedCrossRefGoogle Scholar
  13. 13.
    Hu Q, Yang C, Wang Q, Zeng H, Qin W (2015) Demethylzeylasteral (T-96) Treatment ameliorates mice lupus nephritis accompanied by inhibiting activation of NF-kappaB pathway. PLoS One 10(7):e0133724PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Han R, Rostami-Yazdi M, Gerdes S, Mrowietz U (2012) Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol 74(3):424–436PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Hoyle GW, Hoyle CI, Chen J, Chang W, Williams RW, Rando RJ (2010) Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation. Am J Phys Lung Cell Mol Phys 298(6):L830–L836Google Scholar
  16. 16.
    Lv M, Deng J, Tang N, Zeng Y, Lu C (2018) Efficacy and safety of Tripterygium Wilfordii Hook F on psoriasis vulgaris: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med 2018:2623085PubMedPubMedCentralGoogle Scholar
  17. 17.
    Wang B, Ma L, Tao X, Lipsky PE (2004) Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum 50(9):2995–2303PubMedCrossRefGoogle Scholar
  18. 18.
    van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 65(11):2737–2747PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Masi AT, Rodnan GP, Medsger TA (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 23(5):581–590CrossRefGoogle Scholar
  20. 20.
    Le Pavec J, Launay D, Mathai SC, Hassoun PM, Humbert M (2011) Scleroderma lung disease. Clin Rev Allergy Immunol 40(2):104–116PubMedCrossRefGoogle Scholar
  21. 21.
    Fernandez-Codina A, Walker KM, Pope JE (2018) Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheum 70(11):1820–1828CrossRefGoogle Scholar
  22. 22.
    Antoniu SA (2007) Cyclophosphamide for scleroderma interstitial lung disease. Expert Opin Investig Drugs 16(3): 393-395. PubMedCrossRefGoogle Scholar
  23. 23.
    Schulz S, Bischoff L, Michel D, Derk CT (2006) Scleroderma lung disease: treatment with cyclophosphamide. Expert Rev Clin Immunol 2(6):849–852PubMedCrossRefGoogle Scholar
  24. 24.
    Clements PJ, Roth MD, Elashoff R et al (2007) Scleroderma lung study (SLS): differences in the presentation and course of patients with limited versus diffuse systemic sclerosis. Ann Rheum Dis 66(12):1641–1647PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Khanna D, Tashkin DP, Denton CP, Lubell MW, Vazquez-Mateo C, Wax S (2018) Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease. Rheumatology (Oxford) 58(4):567–579CrossRefGoogle Scholar
  26. 26.
    Launay D, Buchdahl AL, Berezné A, Hatron PY, Hachulla E, Mouthon L (2016) Mycophenolate mofetil following cyclophosphamide in worsening systemic sclerosis-associated interstitial lung disease. J Scleroderma Relat Disord 1(2):234–240CrossRefGoogle Scholar
  27. 27.
    Abraham DJ, Vancheeswaran R, Dashwood MR et al (1997) Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 151(3):831–841PubMedPubMedCentralGoogle Scholar
  28. 28.
    Bhattacharyya S, Kelley K, Melichian DS et al (2013) Toll-like receptor 4 signaling augments transforming growth factor-beta responses: a novel mechanism for maintaining and amplifying fibrosis in scleroderma. Am J Pathol 182(1):192–205PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Wei D, Huang Z (2014) Anti-inflammatory effects of triptolide in LPS-induced acute lung injury in mice. Inflammation 37(4):1307–1316PubMedCrossRefGoogle Scholar
  30. 30.
    Law SK, Simmons MP, Techen N et al (2011) Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.). Phytochemistry 72(1):21–26PubMedCrossRefGoogle Scholar
  31. 31.
    Brinker AM, Ma J, Lipsky PE, Raskin I (2007) Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry 68(6):732–766PubMedCrossRefGoogle Scholar
  32. 32.
    Lei W, Jian L (2012) Changes of CD4(+) CD25(+) Regulatory T Cells, FoxP3 in adjuvant arthritis rats with damage of pulmonary function and effects of tripterygium glycosides tablet. Int J Rheumatol 2012:348450PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Shi YL, Bai JP, Wang WP (2003) Ion-channels in human sperm membrane and contraceptive mechanisms of male antifertility compounds derived from Chinese traditional medicine. Acta Pharmacol Sin 24(1):22–30PubMedGoogle Scholar
  34. 34.
    Gu J, Zhu C, Wang W, Wang L (2001) The effects of Lei Gong Teng on reproductive hormones. J Tradit Chin Med 21(1):50–51PubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Department of Rheumatology and Clinical Immunology, Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina

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