Efficacy and safety of oral high-trough level tacrolimus in acute/subacute interstitial pneumonia with dermatomyositis

Int J Rheum Dis. 2019 Feb;22(2):303-313. doi: 10.1111/1756-185X.13414. Epub 2018 Nov 5.

Abstract

Objectives: We assessed the efficacy and safety of combination therapy with glucocorticoids and high-trough level tacrolimus (TAC) for the treatment of acute/subacute interstitial pneumonia (A/SIP) in patients with dermatomyositis (DM).

Methods: Eleven DM-A/SIP patients were enrolled. The combination therapy with glucocorticoids and TAC was started as early as possible after DM-A/SIP was diagnosed. We monitored the trough concentration of TAC. In the initial 3 months, we maintained the trough concentration of TAC at relatively high levels within a range of 15-20 ng/mL. Then, we decreased the TAC doses stepwise to keep the trough concentration at 10-15 ng/mL in the next 3 months and 5-10 ng/mL as a maintenance dose.

Results: Seven patients had clinically amyopathic DM. Six patients were positive for anti-aminoacyl-tRNA synthetase antibody and two were positive for anti-melanoma differentiation-associated gene 5 antibody. Ten patients survived for the period of the 24-week follow up. One patient died under a tentative diagnosis of viral encephalitis at 4 months after the treatment. In the 10 surviving patients, interstitial pneumonia improved in eight patients and was not worse in two patients. Clinical examinations, including the Krebs von den Lungen-6 levels, % forced vital capacity, and chest computed tomography score, were significantly improved by this combination therapy. Although grade 1 and 2 renal damage occurred in 4 and 2 patients, respectively.

Conclusions: The present findings suggest that early therapeutic intervention by a combination with glucocorticoids and initial high-trough level TAC is effective for DM-A/SIP although consideration of the risks of infection and renal damage is required.

Keywords: dermatomyositis; interstitial pneumonia; tacrolimus; treatment.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Dermatomyositis / complications*
  • Dermatomyositis / diagnosis
  • Drug Monitoring
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / drug therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Tacrolimus / blood
  • Time Factors
  • Treatment Outcome

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Tacrolimus

Supplementary concepts

  • Amyopathic dermatomyositis