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Mycophenolate mofetil treatment with or without a calcineurin inhibitor in resistant inflammatory myopathy

  • Hironari Hanaoka
  • Harunobu Iida
  • Tomofumi Kiyokawa
  • Yukiko Takakuwa
  • Kimito Kawahata
Brief Report
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Abstract

To evaluate the efficacy and tolerability of mycophenolate mofetil (MMF) with or without calcineurin inhibitors (CNIs) in patients with inflammatory myopathy taking prednisolone, but refractory to conventional immunosuppressive therapy. The records of patients with inflammatory myopathy who had previously failed treatment with at least one immunosuppressant were retrospectively evaluated. We selected patients treated with MMF and divided them into two groups depending on whether or not there was concomitant use of CNIs. We investigated the efficacy by changes in creatine kinase (CK) levels, forced vital capacity (%FVC), prednisolone dose, and high-resolution computed tomography (HRCT) findings. Interstitial lung disease (ILD) progression was defined by more than 10% decline of %FVC from baseline. We identified 19 patients on MMF treatment. There were seven (36.8%) patients on MMF and CNIs, including five on cyclosporine and two on tacrolimus. At baseline, no significant difference was seen in the prevalence of ILD between patients taking or not taking CNIs (85.7% vs. 75.0%, P = 0.68). Improvement in CK was seen in patients treated with CNIs (P = 0.04) but not in those without (P = 0.39). No significant improvement in %FVC and HRCT findings were found in patients with ILD in either group, and there were no differences in death or ILD progression. The combination of CNIs and MMF might be more effective for decreasing CK levels than MMF alone. Neither treatment arm had a beneficial effect on ILD over a variable observation period.

Keywords

Dermatomyositis Drug therapy Inflammatory myopathy/CO Interstitial lung disease Mycophenolate mofetil Polymyositis Tacrolimus 

Notes

Compliance with ethical standards

This study was approved by the Ethics Committee of St. Marianna University School of Medicine (approval number 3502). Since this study was conducted under a retrospective cohort design without any samples taken besides those for clinical use, written informed consent was not required, in accordance with the guidelines of the Ministry of Health, Labour, and Welfare of Japan.

Disclosures

None.

References

  1. 1.
    Dalakas MC (2015) Inflammatory muscle diseases. N Engl J Med 372:1734–1747CrossRefGoogle Scholar
  2. 2.
    Moghadam-Kia S, Aggarwal R, Oddis CV (2015) Treatment of inflammatory myopathy: emerging therapies and therapeutic targets. Expert Rev Clin Immunol 11:1265–1275CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D, the Aspreva Lupus Management Study Group (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, Chen J, Lin H, Liu F, He Y, He Y, Miao L, Chen N, Li Y, Gu Y, Shi W, Hu W, Liu Z, Bao H, Zeng C, Zhou M (2015) Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med 162:18–26CrossRefPubMedGoogle Scholar
  5. 5.
    Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER et al (2013) Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. J Rheumatol 40:640–646CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pisoni CN, Cuadrado MJ, Khamashta MA, Hughes GR, D’Cruz DP (2007) Mycophenolate mofetil treatment in resistant myositis. Rheumatology (Oxford) 46:516–518CrossRefGoogle Scholar
  7. 7.
    Rowin J, Amato AA, Deisher N, Cursio J, Meriggioli MN (2006) Mycophenolate mofetil in dermatomyositis: is it safe? Neurology 66:1245–1247CrossRefPubMedGoogle Scholar
  8. 8.
    Majithia V, Harisdangkul V (2005) Mycophenolate mofetil (CellCept): an alternative therapy for autoimmune inflammatory myopathy. Rheumatology (Oxford) 44:386–389CrossRefGoogle Scholar
  9. 9.
    Schneider C, Gold R, Schäfers M, Toyka KV (2002) Mycophenolate mofetil in the therapy of polymyositis associated with a polyautoimmune syndrome. Muscle Nerve 25:286–288CrossRefPubMedGoogle Scholar
  10. 10.
    Danieli MG, Calcabrini L, Calabrese V, Marchetti A, Logullo F, Gabrielli A (2009) Intravenous immunoglobulin as add on treatment with mycophenolate mofetil in severe myositis. Autoimmun Rev 9:124–127CrossRefPubMedGoogle Scholar
  11. 11.
    Bohan A, Peter JB (1975) Polymyositis and dermatomyositis. N Engl J Med 292:344–347CrossRefGoogle Scholar
  12. 12.
    Harris-Love MO, Shrader JA, Koziol D, Pahlajani N, Jain M, Smith M, Cintas HL, McGarvey CL, James-Newton L, Pokrovnichka A, Moini B, Cabalar I, Lovell DJ, Wesley R, Plotz PH, Miller FW, Hicks JE, Rider LG (2009) Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis. Rheumatology (Oxford) 48:134–139CrossRefGoogle Scholar
  13. 13.
    Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, Brown K, Flaherty K, Wells AU, Seibold JR, Strand V (2015) Connective tissue disease-associated interstitial lung diseases (CTD-ILD) - report from OMERACT CTD-ILD Working Group. J Rheumatol 42:2168–2171CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yamasaki Y, Yamada H, Yamasaki M, Ohkubo M, Azuma K, Matsuoka S, Kurihara Y, Osada H, Satoh M, Ozaki S (2007) Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/ dermatomyositis. Rheumatology (Oxford) 46:124–130CrossRefGoogle Scholar
  15. 15.
    Joffe MM, Love LA, Leff RL, Fraser DD, Targoff IN, Hicks JE, Plotz PH, Miller FW (1993) Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med 94:379–387CrossRefPubMedGoogle Scholar
  16. 16.
    Oddis CV, Sciurba FC, Elmagd KA, Starzl TE (1999) Tacrolimus in refractory polymyositis with interstitial lung disease. Lancet 353:1762–1763CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Sugihara T, Sekine C, Nakae T, Khyama K, Harigai M, Iwakura Y et al (2007) A new murine model to define the critical pathologyc and therapeutic mediators of polymyositis. Arthritis Rheum 56:1304–1314CrossRefPubMedGoogle Scholar
  18. 18.
    Chiu YE, Co DO (2011) Juvenile dermatomyositis: immunopathogenesis, role of myositis-specific autoantibodies, and review of rituximab use. Pediatr Dermatol 28:357–367CrossRefPubMedGoogle Scholar
  19. 19.
    Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE, and the RIM Study Group (2013) Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthtitis Rheum 65:314–324CrossRefGoogle Scholar
  20. 20.
    Aggarwal R, Rider LG, Ruperto N, Bayat N, Erman B, Feldman BM et al (2017) International Myositis Assessment and Clinical Studies Group and the Paediatric Rheumatology International Trials Organisation. 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. Arthritis Rheumatol 69:898–910CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Division of Rheumatology and Allergology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan

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