Current Treatment Options in Neurology

, Volume 13, Issue 3, pp 311–323 | Cite as

Immunotherapy of Inflammatory Myopathies: Practical Approach and Future Prospects

  • Marinos C. Dalakas

Opinion statement

The inflammatory myopathies, a group of chronic myopathic conditions, are potentially treatable, so proper diagnosis and early initiation of therapy are necessary. The most common types are polymyositis (PM), dermatomyositis (DM), necrotizing autoimmune myopathy (NAM), and inclusion body myositis (IBM). This review provides practical advice on treatment and identifies emerging new therapies. Although IBM is difficult to treat, PM, DM, and NAM respond to appropriate immunotherapies, if diagnosed early and treated aggressively. In uncontrolled studies, PM and DM respond to prednisone to some degree and for a period of time. The commonly used immunosuppressive drugs (azathioprine, cyclosporine, mycophenolate, or methotrexate) may offer some non-evidence-based “steroid-sparing” effect but provide minimal benefit on their own. As a result, the second-line therapy is intravenous immunoglobulin (IVIg), which a controlled study has shown to be effective in DM and which appears to be effective in PM and NAM; it offers minimal and transient benefit to only a small number of IBM patients, however. Uncontrolled series have suggested that rituximab and tacrolimus may offer additional benefit to some patients not adequately controlled with the aforementioned therapies. IBM is usually resistant to most therapies, but early initiation of therapy may be helpful at times. Emerging agents against T cells, B cells, transmigration, or transduction molecules are discussed as potential new treatment options.


Tacrolimus Alemtuzumab Natalizumab Fingolimod Eculizumab 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Conflicts of Interest: M. Dalakas: Speaker and member of steering committees for Talecris, Octapharma, Baxter, and Genentech.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991;325:1487–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Engel AG, Hohlfeld R, Banker BQ. Polymyositis and dermatomyositis. In: Engel A, editor. Myology, 1335–1383. 3rd ed. New York: McGraw-Hill; 2006.Google Scholar
  3. 3.•
    Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol. 2010;10:346–52. This is an up-to-date, balanced review on inflammatory myopathies.Google Scholar
  4. 4.
    Mastaglia FL, Phillips BA. Idiopathic inflammatory myopathies: epidemiology, classification and diagnostic criteria. Rheum Dis Clin North Am. 2002;28:723–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362:971–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Dalakas MC, Karpati G. The inflammatory myopathies. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC, editors. Disorders of voluntary muscle. 8th ed. Cambridge: Cambridge University Press; 2010. p. 427–52.Google Scholar
  7. 7.
    Dalakas MC. Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies. Nat Clin Pract Neurol. 2006;2437–47.Google Scholar
  8. 8.
    Needham M, Mastaglia FL. Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches. Lancet Neurol. 2007;6:620–31.PubMedCrossRefGoogle Scholar
  9. 9.
    Griggs RC, Askanas V, DiMauro S, et al. Inclusion body myositis and myopathies. Ann Neurol. 1995;38:705–13.PubMedCrossRefGoogle Scholar
  10. 10.
    Askanas V, Engel WK, Nogalska A. Inclusion body myositis: a degenerative muscle disease associated with intra-muscle fiber multi-protein aggregates, proteasome inhibition, endoplasmic reticulum stress and decreased lysosomal degradation. Brain Pathol. 2009;19:493–506.PubMedCrossRefGoogle Scholar
  11. 11.
    Dalakas MC. Mechanisms of disease: signaling pathways and immunobiology of inflammatory myopathies. Nat Clin Pract Rheumatol. 2006;2:219–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Kissel JT, Mendell JR, Rammohan KW. Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med. 1986;314:329–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Wiendl H, Hohlfeld R, Kieseier BC. Immunobiology of muscle: advances in understanding an immunological microenvironment. Trends Immunol. 2005;26:373–80.PubMedCrossRefGoogle Scholar
  14. 14.•
    Dalakas MC. An update on inflammatory and autoimmune myopathies. Neuropath Appl Neurobiol. 2010 Dec 14 (Epub ahead of print). This is a recent review on the diagnosis and immunopathology of PM, DM, IBM and NAM.Google Scholar
  15. 15.
    Karpati G, Pouliot Y, Carpenter S. Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. Ann Neurol. 1988;23:64–72.PubMedCrossRefGoogle Scholar
  16. 16.
    Goebels N, Michaelis D, Engelhardt M, et al. Differential expression of perforin in muscle-infiltrating T cell in polymyositis and dermatomyositis. J Clin Invest. 1996;97:2905.PubMedCrossRefGoogle Scholar
  17. 17.
    Confalonieri P, Oliva L, Andreetta F, et al. Muscle inflammation and MHC class I up-regulation in muscular dystrophy with lack of dysferlin: an immunopathological study. J Neuroimmunol. 2003;142:130–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Engel AG, Arahata K. Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies. Hum Pathol. 1986;17:702–21.Google Scholar
  19. 19.
    Greenberg SA, Pinkus GS, Amato AA, Pinkus JL. Myeloid dendritic cells in inclusion-body myositis and polymyositis. Muscle Nerve. 2007;35:17–23.PubMedCrossRefGoogle Scholar
  20. 20.
    De Bleecker JL, De Paepe B, Vanwalleghem IE, Schröder JM. Differential expression of chemokines in inflammatory myopathies. Neurology. 2002;58:1779–85.PubMedGoogle Scholar
  21. 21.
    Figarella-Branger D, Civate M, Bartoli C, Pellissier JF. Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies. Muscle Nerve. 2003;28:659–82.PubMedCrossRefGoogle Scholar
  22. 22.•
    Mammen AL, Casciola-Rosen LA, Hall JC, et al. Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle. Arthritis Rheum. 2009, 60(12):3784–93. This important study demonstrates that the autoantibody against chromatin remodeler Mi-2, which is present in some DM patients, is strongly immunolocalized in the perifascicular fibers and also in the regenerating muscle in vivo. The study confirms that the perifascicular atrophic fibers are indeed regenerating and that Mi-2 may play a role in myofiber stability during the regeneration process.Google Scholar
  23. 23.•
    Dalakas MC. Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheumatol. 2010;6(3):129–37. This is an up-to-date, critical review of current therapies in myositis.Google Scholar
  24. 24.
    Dalakas MC. Therapeutic approaches in patients with inflammatory myopathies. Semin Neurol. 2003;23(2):199–206.PubMedCrossRefGoogle Scholar
  25. 25.
    Dalakas MC. Therapeutic advances and future prospects in immune-mediated inflammatory myopathies. Ther Adv Neurol Disord. 2008;1(3):157–66.PubMedCrossRefGoogle Scholar
  26. 26.•
    Dalakas MC. Toxic and drug-induced myopathies. J Neurol Neurosurg Psychiatry. 2009;80(8):832–8. The various drugs, especially statins, that trigger myopathies are reviewed, and a differential diagnosis is provided.Google Scholar
  27. 27.•
    Chahin N, Engel AG. Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM. Neurology 2008;70:418–24. This important study introduced the concept of PM/IBM and demonstrated that up to 15% of patients with clinical features of IBM do not have vacuoles or amyloid deposits in their biopsy specimens.Google Scholar
  28. 28.
    Blume G, Pestronk A, Frank B, Johns DR. Polymyositis with cytochrome oxidase negative muscle fibres. Early quadriceps weakness and poor response to immunosuppressive therapy. Brain. 1997;120:39–45.PubMedCrossRefGoogle Scholar
  29. 29.
    Miller FW, Leitman SF, Cronin ME, et al. Controlled trial of plasma exchange and leukapheresis in patients with polymyositis and dermatomyositis. N Engl J Med. 1992;326:1380–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Mastaglia FL, Phillips BA, Zilko PJ. Treatment of inflammatory myopathies. Muscle Nerve. 1997;20:651–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Dalakas MC. Current treatment of the inflammatory myopathies. Curr Opin Rheumatol. 1994;6:595–601.PubMedCrossRefGoogle Scholar
  32. 32.
    Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immunoglobulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;329:1993–2000.PubMedCrossRefGoogle Scholar
  33. 33.
    Hughes RAC, Dalakas MC, Cornblath DR, et al. Clinical applications of intravenous immunoglobulins in neurology. Clin Exp Immunol. 2009;158 Suppl 1:34–42.PubMedCrossRefGoogle Scholar
  34. 34.
    Mastaglia FL, Phillips BA, Zilko PJ. Immunoglobulin therapy in inflammatory myopathies. J Neurol Neurosurg Psychiatry. 1998;65:107–10.PubMedCrossRefGoogle Scholar
  35. 35.
    Chérin P. Current therapy for polymyositis and dermatomyositis. Rev Méd Interne. 2008;29(Spec No 2):9–14.PubMedGoogle Scholar
  36. 36.
    Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19):2367–75.PubMedCrossRefGoogle Scholar
  37. 37.
    Dalakas MC. B cells as a therapeutic target in autoimmune neurological disorders. Nat Clin Pract Neurol. 2008;4(10):557–67.PubMedCrossRefGoogle Scholar
  38. 38.
    Levine TD. Rituximab in the treatment of dermatomyositis: an open label pilot study. Arthritis Rheum. 2005;52:601–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Chung L, Genovese MC, Fiorentino DF. A pilot trial of rituximab in the treatment of patients with dermatomyositis. Arch Dermatol. 2007;143(6):763–7.PubMedCrossRefGoogle Scholar
  40. 40.•
    Kosmidis ML, Dalakas MC. Practical considerations on the use of rituximab in autoimmune neurological disorders. Ther Adv Neurol Disord. 2010;3(2):93–105. This is an up-to-date review on the uses of rituximab in neurologic disorders.Google Scholar
  41. 41.
    Oddis CV, Sciurba FC, Elmagd KA, et al. Tacrolimus in refractory polymyositis with interstitial lung disease. Lancet. 1999;353:1762–3.PubMedCrossRefGoogle Scholar
  42. 42.
    Dalakas MC, Sonies B, Dambrosia J, et al. Treatment of inclusion body myositis with IVIg: a double-blind, placebo-control study. Neurology. 1997;48:712–6.PubMedGoogle Scholar
  43. 43.
    Walter MC, Lochmuller H, Toepfer M, et al. High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study. J Neurol. 2000;247:22–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Cherin P, Pelletier S, Teixeira A, et al. Intravenous immunoglobulin for dysphagia of inclusion body myositis. Neurology. 2002;58:326.PubMedGoogle Scholar
  45. 45.••
    Schmidt J, Barthel K, Wrede A, et al. Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. Brain 2008;131:1228–40. This important study demonstrates the interrelationship between inflammation and degeneration. Functional studies confirm that exposure of muscle cells to pro-inflammatory cytokines induces an overexpression of APP with subsequent accumulation of amyloid aggregates.Google Scholar
  46. 46.•
    Dalakas MC. Interplay between inflammation and degeneration: using inclusion body myositis to study neuroinflammation. Ann Neurol. 2008;64:1–3. This critical editorial emphasizes the concept of neuroinflammation in IBM based on the cross-talk between inflammatory and degenerative molecules.Google Scholar
  47. 47.••
    Muth IE, Barthel K, Bähr M, et al. Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of alphaB-crystallin is associated with amyloid precursor protein and accumulation of beta-amyloid. J Neurol Neurosurg Psychiatry 2009;80:1344–9. The authors convincingly demonstrate that αB-crystallin is, along with proinflammatory markers, an early event associated with cell stress-response that precedes accumulation of β-amyloid.Google Scholar
  48. 48.•
    Dalakas MC, Rakocevic G, Schmidt J, et al. Effect of alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009;132:1536–44. This excellent clinicopathologic proof-of-principle study demonstrates that depletion of T cells from the periphery results in suppression of endomysial inflammation and some degeneration-associated molecules, along with short-term clinical stability. The study, although small and uncontrolled, is important because future antilymphocyte therapies may have an effect not only on inflammatory mediators but also in halting degeneration.Google Scholar
  49. 49.
    Pruitt 2nd JN, Showalter CJ, Engel AG. Sporadic inclusion body myositis: counts of different types of abnormal fibers. Ann Neurol. 1996;39:139–43.PubMedCrossRefGoogle Scholar
  50. 50.••
    vLayzer R, Lee HS, Iverson D, Margeta M. Dermatomyositis with inclusion body myositis pathology. Muscle Nerve. 2009;40(3):469–71. This single case report is significant because it presents a patient with DM with pathologic features of IBM, supporting the concept that intense inflammation may trigger the typical pathologic features of IBM and that early initiation of anti-inflammatory therapy may arrest progression to clinical IBM.Google Scholar
  51. 51.
    Dalakas MC. Therapeutic targets in patients with inflammatory myopathies: present approaches and a look to the future. Neuromuscul Disord. 2006;16:223–36.PubMedCrossRefGoogle Scholar
  52. 52.
    Wiendl H. Idiopathic inflammatory myopathies: current and future therapeutic options. Neurotherapeutics. 2008;5(4):548–57.PubMedCrossRefGoogle Scholar
  53. 53.
    Hohlfeld R, Dalakas MC. Basic principles of immunotherapy in neurological diseases. Semin Neurol. 2003;23:121–32.PubMedCrossRefGoogle Scholar
  54. 54.
    Thomson B, Corris P, Miller JAL, Cooper RG. Alemtuzumab (Campath) in the treatment of refractory polynyositis. J Rheumatol. 2008;35:2080–1.Google Scholar
  55. 55.
    Hengstman GJ, van den Hoogen FH, Barrera P, et al. Successful treatment of dermatomyositis and polymyositis with anti-tumor necrosis factor-alpha: preliminary observations. Eur Neurol. 2003;50:10–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Labioche I, Liozon E, Weschler B, et al. Refractory polymyositis responding to infliximab: extended follow-up. Rheumatology (Oxford). 2004;43:531–2.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Neuroimmunology Unit, Department of PathophysiologyUniversity of Athens Medical SchoolAthensGreece

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