rheumatology and
musculoskeletal
Novel treatments in the
management of myositis
This review focuses on novel treatments in the management
of myositis, incuding recent clinical trial data
Anai Hamasaki MD
Mazen Dimachkie MD
Department of
Neurology, The University
of Kansas Medical Center,
USA
Pedro Machado
MD PhD
MRC Centre for
Neuromuscular Diseases,
University College
London, UK
Idiopathic inflammatory myopathies (IIMs)
comprise a group of autoimmune muscle
disorders including polymyositis (PM),
dermatomyositis (DM), immune-mediated
necrotising myopathy (IMNM) and possibly
inclusion body myositis (IBM). There are some
similarities in clinical presentation with proximal
symmetric muscle weakness in PM, DM and
IMNM; with the exception of IBM, which presents
with distal arm and proximal leg asymmetric
muscle weakness, finger flexor and knee extensor
weakness being characteristic early clinical
features of the disease. The elevation of creatine
kinase and the evidence of irritative myopathy
in the electromyographic study are commonly
present in IIMs. Histopathological findings can
vary significantly among the IIM types, but some
overlap can be seen particularly in PM and IBM
patients. This heterogeneity can also be
observed in the response to treatment, which
leads to the placement of IBM in an isolated
treatment group.
Principles of inflammatory myopathy
treatment
Although the triggers of inflammatory muscle
diseases have not been elucidated, it is believed
that the pathologic mechanism involves an
autoimmune process.
In DM, there is activation and deposition of
complement C5b-9 attack complex on the
endothelial cells and activation of B cells, CD4+
T-cells and plasmacytoid dendritic cells. 1 In PM
and IBM, there is evidence of CD8+ T cells-MHC
class I complex expression in muscle biopsy. In
addition to the inflammatory component in IBM,
other pathogenic mechanisms have been
proposed suggesting a multifactorial process.
These include environmental factors (for
example, viral infection), ageing, genetic
susceptibility, accumulation of toxic proteins,
myonuclear degeneration, endoplasmic reticulum
stress, impairment of autophagy, disruption of
the ubiquitin-proteasome system, myostatin
signalling impairment, mitochondrial dysfunction
and alteration of nucleic acid metabolism. 2 The
evidence of a degenerative process in the
pathogenesis of IBM includes protein
accumulation, namely β-amyloid precursor
protein (β-APP), heat shock proteins (HSPs),
phosphorylated tau (p-Tau), p62, and the
cytoplasmic mis-localisation of RNA-binding
proteins including transactive response DNA
binding protein 43 (TDP-43), heterogeneous
nuclear ribonucleoprotein A1 (hnRNPA1), and
hnRNPA2B1. 1,3,4
Current treatment approaches
Despite the lack of controlled trials, the
current standard treatment for inflammatory
myopathies consists of high-dose steroids,
which is the first-line treatment for DM, PM,
and IMNM. IBM is notoriously refractory to
immunosuppressive treatment. Additional
treatment can be done using second-line agents,
physical, occupational, speech, and swallowing
therapies. 3
A proposed regimen of steroid therapy is
prednisone 60mg/day (or 0.75mg/kg/day to 1.5mg/
kg/day) as starting dose, 3 up to 80–100mg/day. 1
The duration of the starting dose depends on
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