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
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