Idiopathic inflammatory myopathies - Emerging treatments

Janus kinase (JAK) inhibitors

Given the high signature of type 1 interferon in the pathogenesis of dermatomyositis, therapeutic regimes targeting type 1 interferon have either been experimented or are in development.[110] One open-label, clinical trial using the JAK inhibitor tofacitinib in patients with refractory dermatomyositis patients has shown sustained clinical efficacy and reduction of type 1 interferon signature at 96 weeks.[111] Several clinical trials are underway investigating the efficacy of baricitinib, a selective JAK1 and JAK2 inhibitor, in patients with dermatomyositis.[112][113] Inhibition of the JAK-STAT pathway in patients with anti-MDA5 antibody-positive dermatomyositis, in particular with rapidly progressive interstitial lung disease, has shown promising results.[114][115][116]

Plasmapheresis

Plasmapheresis has been used in severe cases of idiopathic inflammatory myopathy, especially in anti-MDA5 dermatomyositis with rapidly progressive interstitial lung disease patients, as up-front treatment or in the treatment of refractory cases.[79][115] This treatment has been combined with drugs such as rituximab and tofacitinib.[115]

Neonatal fragment crystallisable (Fc) receptor (FcRn) inhibitors

FcRn extends the half-life of IgG through a recycling mechanism and prevents degradation of IgG. By blocking the interaction between IgG and FcRn, the downstream effects of pathogenic IgG are then prevented and the titres of these disease-causing IgG are reduced.[117] FcRn inhibitors undergoing phase 2/3 clinical trials targeting patients with dermatomyositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome include nipocalimab and efgartigimod.[118][119][120]

Antifibrotics

Both pirfenidone and nintedanib are immunomodulatory agents that exhibit antifibrotic properties through inhibition of fibroblast activation and proliferation. While no large, randomized trials have assessed the efficacy of antifibrotics in idiopathic inflammatory myopathy-associated interstitial lung disease, smaller series do exist and imply that antifibrotics may have benefit in idiopathic inflammatory myopathy-associated interstitial lung disease.[121][122][123]

Therapies for inclusion body myositis

Killer cell lectin-like receptor G1 (KLRG1) is a surface marker of CD8+ T cells implicated in the pathology of inclusion body myositis.[110] Phase 1 trials using ABC008, a monoclonal antibody that targets KLRG1, in inclusion body myositis patients have shown promising results.[124] Inhibition of mammalian target of rapamycin (mTOR) using sirolimus to inhibit T cell activation and proliferation have also shown promising results in slowing and stabilizing inclusion body myositis disease progression.[125]

Chimeric antigen receptor (CAR) T-cell immunotherapy

Following the success of engineered T cells targeting CD19+ B cells in treating refractory systemic lupus erythematosus and systemic sclerosis, a trials on CAR T-cell therapy in idiopathic inflammatory myopathy patients is on-going.[126][127][128]