Medication Summary
Therapy for polymyositis is based on immune suppression, starting with corticosteroids. Prednisone is the first-line treatment of choice. Immunosuppressive agents are indicated in patients who do not improve with steroids within a reasonable period (ie, 4 weeks) or who experience adverse effects from corticosteroids. Newer agents such as rituximab are showing promise. [36]
Corticosteroids
Class Summary
These agents inhibit the inflammatory process via multiple mechanisms, including the inhibition of proinflammatory cytokine production, monocyte/macrophage function, and angiogenesis.
Prednisone
Prednisone is an anti-inflammatory and immunosuppressive agent used in the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing neutrophilic activity. Prednisone also stabilizes the lysosomal membrane and suppresses lymphocytes, reducing cytokine and antibody production.
Corticotropin (Acthar Gel, HP Acthar Gel)
Porcine ACTH, stimulates adrenocortical hormone production
Immunosuppressants
Class Summary
These agents may be of benefit in patients whose condition has not responded to steroids or in patients unable to tolerate prednisone.
Methotrexate (Rheumatrex, Trexall)
Methotrexate has an unknown mechanism of action in the treatment of chronic inflammatory diseases. It may affect immune function, including through inhibition of the production of proinflammatory cytokines. Methotrexate ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response.
Azathioprine (Imuran, Azasan)
Azathioprine is a purine analog that inhibits the synthesis of deoxyribonucleic acid (DNA), RNA, and proteins. It may decrease the proliferation of immune cells, resulting in lower immunologic activity.
IV Immunoglobulin (Privigen, Hizentra, Octogam, Gammagard)
IVIG neutralizes circulating myelin antibodies through anti-idiotypic antibodies. It down-regulates proinflammatory cytokines, including interferon gamma; blocks Fc receptors on macrophages; suppresses helper T and B lymphocytes; and augments suppressor T lymphocytes. IVIG's exact mechanism of action in the treatment of polymyositis is unknown.
Cyclophosphamide
Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal cells such as lymphocytes and neoplastic cells.
Cyclosporine (Sandimmune, Neoral, Gengraf)
Cyclosporine is a cyclic polypeptide that suppresses cell-mediated immune reactions such as delayed hypersensitivity and, to a lesser extent, humoral immunity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs. Cyclosporine selectively inhibits the transcription of interleukin 2, predominantly in helper lymphocytes.
Mycophenolate (CellCept, MMF, Myfortic)
Inhibits T- and B-cell proliferation, as well as antibody production
Tacrolimus (Astagraf XL, Envarsus XR, Hecoria)
Tacrolimus is a calcineurin inhibitor and inhibits the phosphatase activity of calcineurin which leads to inhibition of T cell response to antigens.
DMARDs, TNF Inhibitors
Class Summary
These agents may be used in refractory cases of polymyositis that have failed to respond to conventional therapy with steroids.
Etanercept (Enbrel)
Etanercept binds specifically to TNF and blocks its interaction with cell-surface TNF receptors, rendering TNF biologically inactive.
Infliximab (Remicade)
Infliximab binds to soluble and transmembranous forms of TNF-alpha, rendering TNF biologically inactive.
Anti-CD20 Monoclonal Antibodies
Class Summary
Clinical trials with rituximab have shown encouraging results in patients who are refractory to first-line treatment.
Rituximab (Rituxan)
(Off-label) Rituximab is a humanized monoclonal antibody that binds to CD20 antigen, thereby inducing complement- or antibody-mediated cytolysis. Clinical trials in refractory polymyositis have shown improvement in patients who have failed corticosteroids and other immunosuppressive agents.
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Polymyositis. MRI of thighs showing increased signal in the quadriceps muscles bilaterally consistent with inflammatory myositis.
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Polymyositis. Histopathology slide shows endomysial mononuclear inflammatory infiltrate and muscle fiber necrosis.
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Polymyositis. Close view of muscle biopsy, showing chronic inflammatory infiltrate consisting of T lymphocytes, especially CD8+ T lymphocytes.
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Polymyositis. Hematoxylin and eosin frozen section shows polymyositis. Endomysial chronic inflammation is present among intact myofibers, which are remarkable only for increased variability of fiber size. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Patient had dense endomysial inflammation that contains an abundance of plasma cells, which can be observed in patients with chronic polymyositis. Two necrotic myofibers, characterized by dense eosinophilic staining, are observed. Focal fatty infiltration of the muscle is present in the lower left quadrant of the photomicrograph. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Photomicrograph illustrates attack on a nonnecrotic myofiber by autoaggressive T lymphocytes. On the left, the central myofiber is intact. On the right, it is obliterated by a segmental inflammatory attack. If immunohistochemistry were performed, expected findings would include an admixture of CD8 T lymphocytes and macrophages in the inflammatory process. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in the center has a mild perivascular chronic inflammatory infiltrate. The endothelium is plump. The wall is not necrotic. A few lymphocytes in the wall of the vessel are probably in transit from the lumen to the external aspect of the vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows a dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J. Seidman, MD.
