The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients

Pediatr Rheumatol Online J. 2019 May 22;17(1):24. doi: 10.1186/s12969-019-0326-5.

Abstract

Background: Prednisone (PDN) in juvenile dermatomyositis (JDM), alone or in association with other immunosuppressive drugs, namely methotrexate (MTX) and cyclosporine (CSA), represents the first-line treatment option for new onset JDM patients. No clear evidence based guidelines are actually available to standardize the tapering and discontinuation of glucocorticoids (GC) in JDM. Aim of our study was to provide an evidence-based proposal for GC tapering/discontinuation in new onset juvenile dermatomyositis (JDM), and to identify predictors of clinical remission and GC discontinuation.

Methods: New onset JDM children were randomized to receive either PDN alone or in combination with methotrexate (MTX) or cyclosporine (CSA). In order to derive steroid tapering indications, PRINTO/ACR/EULAR JDM core set measures (CSM) and their median absolute and relative percent changes over time were compared in 3 groups. Group 1 included those in clinical remission who discontinued PDN, with no major therapeutic changes (MTC) (reference group) and was compared with those who did not achieve clinical remission, without or with MTC (Group 2 and 3, respectively). A logistic regression model identified predictors of clinical remission with PDN discontinuation.

Results: Based on the median change in the CSM of 30/139 children in Group 1, after 3 pulses of methyl-prednisolone, GC could be tapered from 2 to 1 mg/kg/day in the first two months from onset if any of the CSM decreased by 50-94%, and from 1 to 0.2 mg/kg/day in the following 4 months if any CSM further decreased by 8-68%, followed by discontinuation in the ensuing 18 months. The achievement of PRINTO JDM 50-70-90 response after 2 months of treatment (ORs range 4.5-6.9), an age at onset > 9 years (OR 4.6) and the combination therapy PDN + MTX (OR 3.6) increase the probability of achieving clinical remission (p < 0.05).

Conclusions: This is the first evidence-based proposal for glucocorticoid tapering/discontinuation based on the change in JDM CSM of disease activity.

Trial registration: Trial full title: Five-Year Single-Blind, Phase III Effectiveness Randomized Actively Controlled Clinical Trial in New Onset Juvenile Dermatomyositis: Prednisone versus Prednisone plus Cyclosporine A versus Prednisone plus Methotrexate. EUDRACT registration number: 2005-003956-37 .

Clinical trial: gov is NCT00323960 . Registered on 17 August 2005.

Keywords: Core set measures; Disease activity; Glucorticoids; Juvenile dermatomyositis; Prednisone tapering.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Analysis of Variance
  • Anti-Inflammatory Agents / administration & dosage*
  • Child
  • Child, Preschool
  • Cyclosporine / administration & dosage*
  • Dermatologic Agents / administration & dosage*
  • Dermatomyositis / drug therapy*
  • Drug Substitution
  • Drug Therapy, Combination
  • Humans
  • Methotrexate / administration & dosage*
  • Prednisone / administration & dosage*
  • Single-Blind Method

Substances

  • Anti-Inflammatory Agents
  • Dermatologic Agents
  • Cyclosporine
  • Prednisone
  • Methotrexate