Treatment of antisynthetase-associated interstitial lung disease with tacrolimus

Arthritis Rheum. 2005 Aug;52(8):2439-46. doi: 10.1002/art.21240.


Objective: To assess the efficacy of tacrolimus in patients with anti-aminoacyl-transfer RNA synthetase (anti-aaRS)-associated interstitial lung disease (ILD) and idiopathic inflammatory myopathy (IIM).

Methods: Ninety-eight patients with anti-aaRS autoantibodies were identified in our IIM cohort of 536 patients. The medical records of 15 patients with anti-aaRS-associated ILD treated with tacrolimus between 1992 and 2003 were retrospectively reviewed. Pulmonary parameters of response included forced vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. Manual muscle testing results, serum creatine kinase (CK) levels, and the daily corticosteroid dosage were used to assess improvement in myositis. Random coefficient modeling considering polynomials of time was used to assess the clinical response to tacrolimus.

Results: All patients, except for 1, who had pure ILD, had definite or probable IIM. Two patients received tacrolimus for fewer than 3 months, and their data were not analyzed. For the remaining 13 patients, the mean age at onset of ILD was 46.9 years, and the mean duration of pulmonary disease was 14.7 months. Twelve patients had anti-histidyl-transfer RNA synthetase autoantibody (anti-Jo-1) and 1 had anti-alanyl-transfer RNA synthetase autoantibody (anti-PL-12). Patients received tacrolimus for an average of 51.2 months. A significant improvement was observed in all pulmonary parameters measured. The serum CK level declined significantly, and 10 patients had either an improvement in muscle strength or maintained normal muscle strength. A statistically significant reduction in the corticosteroid dosage was also observed.

Conclusion: Tacrolimus is a well-tolerated and effective therapy for managing refractory ILD and myositis in anti-aaRS-positive patients.

MeSH terms

  • Adult
  • Aged
  • Alanine-tRNA Ligase / immunology
  • Amino Acyl-tRNA Synthetases / immunology*
  • Autoantibodies / blood*
  • Cohort Studies
  • Female
  • Histidine-tRNA Ligase / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / immunology*
  • Male
  • Middle Aged
  • Myositis / complications
  • Myositis / drug therapy
  • Myositis / immunology
  • Retrospective Studies
  • Tacrolimus / therapeutic use*
  • Treatment Outcome


  • Autoantibodies
  • Immunosuppressive Agents
  • Amino Acyl-tRNA Synthetases
  • Histidine-tRNA Ligase
  • Alanine-tRNA Ligase
  • Tacrolimus