clinical improvement by measuring muscle strength( normalisation or improvement with a plateau). The normalisation of the CK level is sometimes used to guide initiation of prednisone taper; however, the decrease in CK level by itself is not considered a sign of improvement. 5 A slow prednisone taper is recommended after 3 – 4 weeks of high-dose prednisone in patients showing clinical improvement. A proposed prednisone taper is decrease prednisone by 10mg / day every four weeks until the patient is on 20mg / day; then decrease by 5mg / day every four weeks until the patient is on 10mg / day; then decrease by 2.5mg / day every 4 – 12 weeks. Intravenous methylprednisolone 1g / day for three days can be used prior to initiation of high-dose prednisone in patients with severe weakness, prominent extramuscular disease or rapidly worsening disease. 3
Steroid-sparing immunosuppressive or immunomodulating therapy is usually used in patients with moderate to severe diseases or those with medical comorbidities making long-term prednisone use undesirable. The second-line agents usually used in patients with myositis include azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, and intravenous immunoglobulin( IVIg). Treatment of IIMs is further complicated by the presence of extramuscular manifestations of myositis, such as interstitial lung disease( ILD), arthritis and typical skin rashes in DM.
Novel agents Novel agents being evaluated for treatment of myositis include adrenocorticotropic hormone( ACTH) gel, rituximab, IMO-8400, belimumab, Octagam ®, tocilizumab, abatacept, siponimod, JBT-101, IFN-kinoid, anakinra, bimagrumab, follistatin gene therapy, rapamycin, and arimoclomol.
PM and DM ACTH gel, also known as repository corticotropin injection, showed favourable results in a small open-label refractory myositis clinical trial( NCT01906372), being safe and effective and leading to a reduction in concomitant steroid dosing. 6
Rituximab, a monoclonal antibody that targets B-cells, is an approved drug for non- Hodgkin’ s lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis and in the US for microscopic polyangiitis and granulomatosis with polyangiitis. Rituximab for the treatment of refractory adult and juvenile DM and adult PM study was a Phase II clinical trial( RIM trial, 2013, NCT00106184) that showed no significant differences in the two treatment arms( group 1: rituximab followed by placebo; group 2: placebo followed by rituximab) for the primary( time to improve between the groups) and secondary( proportion of improved patients between the groups) end points, but 83 % of adult and juvenile myositis patients with refractory disease met the definition of improvement. 7 An ongoing clinical trial of rituximab in myositis is a randomised, double-blinded, controlled clinical trial comparing rituximab and cyclophosphamide in connective tissue disease associated with
interstitial lung disease( RECITAL, NCT01862926).
IMO-8400 is an antagonist of the toll-like receptor 7, 8 and 9( implicated in immunemediated diseases). 8 Its short-term use has been shown to be well tolerated and to reduce severity of psoriasis. Currently, IMO-8400 is being studied in adult patients with DM( NCT02612857).
Belimumab, a monoclonal antibody against B lymphocyte stimulator( BLyS, a B cell-activating factor), 9 is an approved drug for systemic lupus erythematosus. It is currently being studied in myositis in a multicentre, double-blind, placebocontrolled trial( NCT02347891).
Octagam ® is an intravenous immunoglobulin( IVIg), the mechanism of action of which is to downregulate antibody production by B-cells, interfere with B-cell proliferation and prevent its activation, and downregulate macrophage activity by interrupting complement activation cascade and blocking Fc-receptor-mediated activity. 10 IVIg is approved for use in patients with allogenic bone marrow transplant, chronic lymphocytic leukaemia, idiopathic thrombocytopenic purpura, Kawasaki disease, paediatric HIV and primary immunodeficiencies. More than 150 unlabelled uses of IVIg, which includes myositis, have been described. 11 The ongoing clinical trials of immunoglobulins in myositis include optimising treatment on idiopathic inflammatory myopathies( NCT03092180); a randomised, double-blinded, placebo-controlled Phase III study evaluating
24 HHE 2018 | hospitalhealthcare. com