Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 52, Issue 1, pp 81–87 | Cite as

Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics

  • Siamak Moghadam-Kia
  • Chester V. Oddis
  • Rohit AggarwalEmail author
Article

Abstract

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.

Keywords

Idiopathic inflammatory myopathy Myositis Polymyositis Dermatomyositis Treatment Biologic agents 

References

  1. 1.
    Oddis CV, Reed AM, Aggarwal R et al (2013) Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 65(2):314–324CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bunch TW, Worthington JW et al (1980) Azathioprine with prednisone for polymyositis. A controlled, clinical trial. Ann Intern Med 92(3):365–369CrossRefPubMedGoogle Scholar
  3. 3.
    Dalakas MC, Illa I, Dambrosia JM et al (1993) A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 329(27):1993–2000CrossRefPubMedGoogle Scholar
  4. 4.
    Miller FW, Leitman SF, Cronin ME et al (1992) Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis. N Engl J Med 326(21):1380–1384CrossRefPubMedGoogle Scholar
  5. 5.
    Troyanov Y, Targoff IN, Tremblay JL et al (2005) Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients. Medicine (Baltimore) 84(4):231–249CrossRefGoogle Scholar
  6. 6.
    Koenig M, Fritzler MJ, Targoff IN et al (2007) Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther 9(4):R78CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rider LG, Werth VP, Huber AM et al (2011) Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: physician and patient/parent global activity, manual muscle testing (MMT), health assessment questionnaire (HAQ)/childhood health assessment questionnaire (C-HAQ), childhood myositis assessment scale (CMAS), myositis disease activity assessment tool (MDAAT), disease activity score (DAS), short form 36 (SF-36), child health questionnaire (CHQ), physician global damage, myositis damage index (MDI), quantitative muscle testing (QMT), myositis functional index-2 (FI-2), myositis activities profile (MAP), inclusion body myositis functional rating scale (IBMFRS), cutaneous dermatomyositis disease area and severity index (CDASI), cutaneous assessment tool (CAT), dermatomyositis skin severity index (DSSI), skindex, and dermatology life quality index (DLQI). Arthritis Care Res 63(Suppl 11):S118–S157CrossRefGoogle Scholar
  8. 8.
    Oddis CV, Rider LG, Reed AM et al (2005) International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies. Arthritis Rheum 52(9):2607–2615CrossRefPubMedGoogle Scholar
  9. 9.
    Isenberg DA, Allen E, Farewell V 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):49–54CrossRefGoogle Scholar
  10. 10.
    R Aggarwal, LG Rider, N Ruperto, N Bayat, B Erman, BM Feldman, A Huber, CV Oddis, I Lundberg, AA Amato, RG Cooper, H Chinoy, M Dastmalchi, D Fiorentino, D Isenberg, JD Katz, A Mammen, M de Visser, SR Ytterberg, D. Katalin, L Villa, M Rinaldi, H Rockette, P Lachenbruch, F Miller, J Vencovsky. A (2014) Consensus Hybrid Definition using a Conjoint Analysis is Proposed as Response Criteria for Minimal and Moderate Improvement in Adult Polymyositis and Dermatomyositis Clinical Trials. Arthritis Rheum 64(10 Suppl).Google Scholar
  11. 11.
    Mahler EA, Blom M, Voermans NC et al (2011) Rituximab treatment in patients with refractory inflammatory myopathies. Rheumatology (Oxford) 50(12):2206–2213CrossRefGoogle Scholar
  12. 12.
    Valiyil R, Casciola-Rosen L, Hong G et al (2010) Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series. Arthritis Care Res 62(9):1328–1334CrossRefGoogle Scholar
  13. 13.
    Levine TD (2005) Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 52(2):601–607CrossRefPubMedGoogle Scholar
  14. 14.
    Mok CC, Ho LY, To CH (2007) Rituximab for refractory polymyositis: an open-label prospective study. J Rheumatol 34(9):1864–1868PubMedGoogle Scholar
  15. 15.
    Chung L, Genovese MC, Fiorentino DF (2007) A pilot trial of rituximab in the treatment of patients with dermatomyositis. Arch Dermatol 143(6):763–767CrossRefPubMedGoogle Scholar
  16. 16.
    Brulhart L, Waldburger JM, Gabay C (2006) Rituximab in the treatment of antisynthetase syndrome. Ann Rheum Dis 65(7):974–975CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lambotte O, Kotb R, Maigne G, Blanc FX, Goujard C, Delfraissy JF (2005) Efficacy of rituximab in refractory polymyositis. J Rheumatol 32(7):1369–1370PubMedGoogle Scholar
  18. 18.
    Arlet JB, Dimitri D, Pagnoux C et al (2006) Marked efficacy of a therapeutic strategy associating prednisone and plasma exchange followed by rituximab in two patients with refractory myopathy associated with antibodies to the signal recognition particle (SRP). Neuromuscul Disord 16(5):334–336CrossRefPubMedGoogle Scholar
  19. 19.
    Aggarwal R, Bandos A, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, Miller FW, Rider LG, Harris-Love MO, Levesque MC (2014) RIM Study Group, Oddis CV. Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol 66(3):740–749CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kalluri M, Oddis CV (2010) Pulmonary manifestations of the idiopathic inflammatory myopathies. Clin Chest Med 31:501–512CrossRefPubMedGoogle Scholar
  21. 21.
    Marie I, Hachulla E, Chérin P et al (2002) Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum 47:614–622CrossRefPubMedGoogle Scholar
  22. 22.
    Keir GJ, Maher TM, Ming D et al (2014) Rituximab in severe, treatment-refractory interstitial lung disease. Respirology 19:353–359CrossRefPubMedGoogle Scholar
  23. 23.
    Andersson H, Sem M, Lund MB, Aaløkken TM, Günther A, Walle-Hansen R, Garen T, Molberg Ø (2015) Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease. Rheumatology (Oxford) 54:1420–1428CrossRefGoogle Scholar
  24. 24.
    Cherin P, Pelletier S, Teixeira A et al (2002) Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients. Arthritis Rheum 46(2):467–474CrossRefPubMedGoogle Scholar
  25. 25.
    Danieli MG, Pettinari L, Moretti R, Logullo F, Gabrielli A (2011) Subcutaneous immunoglobulin in polymyositis and dermatomyositis: a novel application. Autoimmun Rev 10(3):144–149CrossRefPubMedGoogle Scholar
  26. 26.
    Miyasaka N, Hara M, Koike T, Saito E, Yamada M, Tanaka Y (2012) GB-0998 Study Group. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial. Mod Rheumatol 22(3):382–393CrossRefPubMedGoogle Scholar
  27. 27.
    Suzuki Y, Hayakawa H, Miwa S et al (2009) Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung 187:201–206CrossRefPubMedGoogle Scholar
  28. 28.
    Bakewell CJ, Raghu G (2011) Polymyositis associated with severe interstitial lung disease: remission after three doses of IV immunoglobulin. Chest 139:441–443CrossRefPubMedGoogle Scholar
  29. 29.
    Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT (2012) Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 78(13):1009–1015CrossRefPubMedGoogle Scholar
  30. 30.
    Iannone F, Scioscia C, Falappone PC et al (2006) Use of etanercept in the treatment of dermatomyositis: a case series. J Rheumatol 33(9):1802–1804PubMedGoogle Scholar
  31. 31.
    Muscle Study Group (2011) A randomized, pilot trial of etanercept in dermatomyositis. Ann Neurol 70(3):427–436CrossRefGoogle Scholar
  32. 32.
    Hengstman GJ, van den Hoogen FH, Barrera P et al (2003) Successful treatment of dermatomyositis and polymyositis with anti-tumor-necrosis-factor-alpha: preliminary observations. Eur Neurol 50(1):10–15CrossRefPubMedGoogle Scholar
  33. 33.
    Selva-O’Callaghan A, Martínez-Costa X, Solans-Laque R et al (2004) Refractory adult dermatomyositis with pneumatosis cystoides intestinalis treated with infliximab. Rheumatology (Oxford) 43(9):1196–1197CrossRefGoogle Scholar
  34. 34.
    Anandacoomarasamy A, Howe G, Manolios N (2005) Advanced refractory polymyositis responding to infliximab. Rheumatology (Oxford) 44(4):562–563CrossRefGoogle Scholar
  35. 35.
    Hengstman GJ, van den Hoogen FH, van Engelen BG (2004) Treatment of dermatomyositis and polymyositis with anti-tumor necrosis factor-alpha: long-term follow-up. Eur Neurol 52(1):61–63CrossRefPubMedGoogle Scholar
  36. 36.
    Efthimiou P, Schwartzman S, Kagen LJ (2006) Possible role for tumour necrosis factor inhibitors in the treatment of resistant dermatomyositis and polymyositis: a retrospective study of eight patients. Ann Rheum Dis 65(9):1233–1236CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dastmalchi M, Grundtman C, Alexanderson H et al (2008) A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis 67(12):1670–1677CrossRefPubMedGoogle Scholar
  38. 38.
    Coyle K, Pokrovnichka A, French K (2008) A randomized double blind placebo controlled trial of infliximab in patients with polymyositis and dermatomyositis. Arthritis Res 58:S293Google Scholar
  39. 39.
    Hengstman GJ, De Bleecker JL, Feist E (2008) Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate. Eur Neurol 59(3–4):159–163CrossRefPubMedGoogle Scholar
  40. 40.
    Riolo G, Towheed TE (2012) Anti-tumor necrosis factor inhibitor therapy-induced dermatomyositis and fasciitis. J Rheumatol 39(1):192–194PubMedGoogle Scholar
  41. 41.
    Klein R, Rosenbach M, Kim EJ et al (2010) Tumor necrosis factor inhibitor-associated dermatomyositis. Arch Dermatol 146(7):780–784CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ishikawa Y, Yukawa N, Ohmura K et al (2010) Etanercept-induced anti-Jo-1-antibody-positive polymyositis in a patient with rheumatoid arthritis: a case report and review of the literature. Clin Rheumatol 29(5):563–566CrossRefPubMedGoogle Scholar
  43. 43.
    Brunasso AM, Scocco GL, Massone C (2010) Dermatomyositis during adalimumab therapy for rheumatoid arthritis. J Rheumatol 37(7):1549–1550CrossRefPubMedGoogle Scholar
  44. 44.
    Lepidi H, Frances V, Figarella-Branger D et al (1998) Local expression of cytokines in idiopathic inflammatory myopathies. Neuropathol Appl Neurobiol 24(1):73–79CrossRefPubMedGoogle Scholar
  45. 45.
    Gabay C, Gay-Croisier F, Roux-Lombard P et al (1994) Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response. Arthritis Rheum 37(12):1744–1751CrossRefPubMedGoogle Scholar
  46. 46.
    Lundberg I, Ulfgren AK, Nyberg P et al (1997) Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. Arthritis Rheum 40(5):865–874CrossRefPubMedGoogle Scholar
  47. 47.
    Narazaki M, Hagihara K, Shima Y (2011) Therapeutic effect of tocilizumab on two patients with polymyositis. Rheumatology (Oxford) 50(7):1344–1346CrossRefGoogle Scholar
  48. 48.
    Kondo M, Murakawa Y, Matsumura T, Matsumoto O, Taira M, Moriyama M, Sumita Y, Yamaguchi S (2014) A case of overlap syndrome successfully treated with tocilizumab: a hopeful treatment strategy for refractory dermatomyositis? Rheumatology (Oxford) 53(10):1907–1908CrossRefGoogle Scholar
  49. 49.
    Thompson B, Corris P, Miller JA et al (2008) Alemtuzumab (Campath-1H) for treatment of refractory polymyositis. J Rheumatol 35(10):2080–2082PubMedGoogle Scholar
  50. 50.
    Murata K, Dalakas MC (1999) Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies. Am J Pathol 155(2):453–460CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Nagaraju K, Raben N, Villalba ML, Danning C, Loeffler LA, Lee E, Tresser N, Abati A, Fetsch P, Plotz PH (1999) Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells. Clin Immunol 92(2):161–169CrossRefPubMedGoogle Scholar
  52. 52.
    Musuruana JL, Cavallasca JA (2011) Abatacept for treatment of refractory polymyositis. Joint Bone Spine 78(4):431–432CrossRefPubMedGoogle Scholar
  53. 53.
    Arabshahi B, Silverman RA, Jones OY, Rider LG (2012) Abatacept and sodium thiosulfate for treatment of recalcitrant juvenile dermatomyositis complicated by ulceration and calcinosis. J Pediatr 160(3):520–522CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Maeshima K, Kiyonaga Y, Imada C, Iwakura M, Hamasaki H, Haranaka M, Ishii K (2014) Successful treatment of refractory anti-signal recognition particle myopathy using abatacept. Rheumatology (Oxford) 53(2):379–380CrossRefGoogle Scholar
  55. 55.
    Kerola AM, Kauppi MJ (2015) Abatacept as a successful therapy for myositis—a case-based review. Clin Rheumatol 34(3):609–612CrossRefPubMedGoogle Scholar
  56. 56.
    Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R, Barohn RJ, Saperstein DS, Briemberg HR, Ericsson M, Park P, Amato AA (2005) Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol 57(5):664–678CrossRefPubMedGoogle Scholar
  57. 57.
    Walsh RJ, Kong SW, Yao Y, Jallal B, Kiener PA, Pinkus JL, Beggs AH, Amato AA, Greenberg SA (2007) Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum 56(11):3784–3792CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, Ytterberg SR, Gregersen PK, Behrens TW, Reed AM (2007) An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol Med 13(1–2):59–68PubMedPubMedCentralGoogle Scholar
  59. 59.
    Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, Ellingson S, Newman B, Bauer JW, Peterson EJ, Baechler EC, Reed AM (2009) Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum 60(11):3436–3446CrossRefPubMedGoogle Scholar
  60. 60.
    Higgs BW, Zhu W, Morehouse C et al (2014) A phase 1b clinical trial evaluating sifalimumab, an anti-IFN-α monoclonal antibody, shows target neutralisation of a type I IFN signature in blood of dermatomyositis and polymyositis patients. Ann Rheum Dis 73(1):256–262CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Siamak Moghadam-Kia
    • 1
  • Chester V. Oddis
    • 1
  • Rohit Aggarwal
    • 1
    Email author
  1. 1.Department of Medicine, Myositis Center and Division of Rheumatology and Clinical ImmunologyUniversity of Pittsburgh School of MedicinePittsburghUSA

Personalised recommendations