Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus
Condition: Interstitial Pneumonitis; Polymyositis; Dermatomyositis
MeSH terms: Pneumonia; Dermatomyositis; Polymyositis; Lung Diseases, Interstitial
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of the study is to evaluate the efficacy and safety of the combination treatment
      of tacrolimus and corticosteroid in polymyositis/dermatomyositis patients with interstitial
      pneumonitis with comparison against corticosteroid-treated historical controls.
    

Detailed description: 
      Interstitial pneumonia (IP) is a common complication of and has a significant impact on the
      prognosis of patients with polymyositis (PM) and dermatomyositis (DM). Reported prevalence of
      IP in PM/DM patients varies between 23 to 65% depending on criteria applied as well as on
      clinical settings of studied cohorts, and an earlier overview and a later study reported its
      high short-term mortality.

      However, treatment for this grave complication has not yet been either established or even
      been prospectively investigated. Glucocorticoids, while long been considered as the
      first-line drugs, is effective in less than 50% of patients. Furthermore, the mortality of
      these glucocorticoids-resistant patients does not improve even if immunosuppressive drugs are
      later added.

      Recently, we and others reported retrospective data which suggest that either an early
      addition of immunosuppressive drugs to glucocorticoids or the combined use of glucocorticoids
      and immunosuppressive drugs from the initial treatment may improve the survival of PM/DM
      patients. To save lives of PM/DM-IP patients, desperate treating physicians have started
      using this approach, strongly urging the conduct of prospective studies to investigate the
      superiority of this approach over glucocorticoids alone. At the same time, it was considered
      not ethically appropriate to conduct a prospective study with a concurrent controlled group
      receiving glucocorticoids alone given the presence of the PM/DM-IP subtype with rapidly
      progressive course and high short-term mortality if treated with glucocorticoids alone and
      the absence of useful demographic or bio-markers which could distinguish patients with this
      subtype early. Among immunosuppressive drugs used in the treatment of PM/DM-IP, tacrolimus
      has recently been suggested to be effective even for those patients who are resistant to
      cyclosporine or cyclosphosphamide.

      To investigate whether the combined initial treatment of glucocorticoids and tacrolimus is
      superior to glucocorticoids alone in PM/DM-IP patients, we conducted a multicenter clinical
      trial to evaluate the efficacy and safety of a combination treatment of glucocorticoids and
      tacrolimus for 1 year in patients with newly developed active PM/DM-IP or its relapse by
      comparing against clinical outcome of historical control patients who were treated with
      glucocorticoid alone as an initial treatment.
    

Intervention name(s): Tacrolimus
Intervention type(s): Drug
Intervention description(s): Start at the standard starting dose of 0.075mg/kg/day divided into two doses, then adjust doses based on clinical response and tolerability, but maintain whole blood trough levels between 5 to 10 ng/mL and total daily doses equal to or below 0.3mg/kg.
Other intervention name(s): Prograf
Intervention MeSH terms: Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Interstitial pneumonitis; Polymyositis; Dermatomyositis; Tacrolimus; Corticosteroids