CARRA Consensus Treatment for Refractory Juvenile Dermatomyositis Save

CARRA has developed consensus treatment plans (CTPs) for the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with refractory, moderately severe juvenile dermatomyositis (JDM). 

Juvenile dermatomyositis is the most common form of idiopathic, inflammatory myositis (IIM) in childhood, with an estimated incidence of 3.2 per million children per year in the United States.

This publication is the work product of the Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Research Committee that used case-based surveys, consensus framework, and nominal group technique to develop these bDMARD CTPs for juvenile dermatomyositis. This CTP addresses the use of 4 bDMARDs: 1) TNF-alpha inhibitor (adalimumab or infliximab), 2) abatacept, 3) rituximab, and 4) tocilizumab; and defines the dosing and/or route.  Recommendations were sent to 100 CARRA members and from 76 respondents, consensus was achieved for the proposed CTPs by 93%. 

These bDMARD CTPs are an important first step in developing registry-based prospective comparative effectiveness studies. Respondents indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab.

These bDMARD CTPs are intended for moderately severe JDM not responding to standard treatment in the initial management of JDM - specifically glucocorticoids, methotrexate, and IVIG. 

CARRA members indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab. They also refractory JDM patients treated with these CTPs should continue at least one cDMARD (MTX, HCQ), steroids and adjunctive IVIG (99% consensus).  

Criteria for use of these CTPs include: 

1. Patients should be younger than 19 years of age at onset and satisfy a diagnosis of definite or probable JDM according to either 1975 Bohan and Peter or 2017 EULAR/ACR classification criteria 
   1. The Bohan and Peter criteria were modified to allow MRI findings consistent with inflammatory myopathy in place of the muscle biopsyor electromyography criterion, 
2. Patients are required to have either failed or been intolerant to: 
   1. Pulse or oral systemic glucocorticoids, 
   2. at least one cDMARD  (e.g.,methotrexate, mycophenolate, azathioprine, cyclosporine, tacrolimus) at optimal dosing for at least 12weeks; or 
   3. IVIG at a dose of 1-2g/kg/month for at least 12 weeks
3. Patient should not have/be: 
   1. Pregnant or breastfeeding
   2. Contraindication to biologic use
   3. Treated with unconventional therapy
   4. Nonadherence with conventional/optimal therapy as determined by the treating physician
   5. Severe systemic disease (e.g., Childhood Myositis Assessment Scale <15 or Manual MuscleTesting-8 <30, myocarditis, central nervous system involvement, gastrointestinal vasculitis, severe dysphagia/aspiration)
   6. Overlap syndromes or mimicking disease
   7. Any prior or current treatment with a biologic medication

Juvenile dermatomyositis biologic DMARD consensus treatment plans

• Treatment A:TNF-α inhibitor
  • Adalimumab (SC) • 20mg every other week for body weight 15 to30kg; 40mg every other week for body weight≥30kg; may increase frequency to every week
  • Infliximab (IV) • 5-10mg/kg (max 1000mg/dose) at week 0 and2, then every 4-8 weeks; loading dose at week 0 is optional• 6mg/kg (max 1000mg/dose) every 4 weeks 
• Abatacept
  • IV • 10mg/kg for body weight <75kg; 750mg for bodyweight 75 to 100kg; 1000mg for body weight>100kg at week 0, 2, 4 and then every 4 weeks; loading dose at week 2 is optional
  • SC • 50mg for body weight 10 to <25kg; 87.5mg for body weight 25-50kg; 125mg for body weight≥50kg every week  
• Rituximab 
  • 575mg/m²/dose for BSA ≤1.5m 2; 750mg/m 2 for BSA >1.5m 2 (max1gm/dose) IV at week 0 and 1. May repeat this regimen every 6 months 
  • 375mg/m 2/dose (max 1gm/dose) IV once weekly for 4 doses. May repeat this regimen or 250mg/m2 once weekly for 2 doses every 6 months
  • 500mg/m2/dose (max 1gm/dose) IV. May repeat this regimen every 6 months
• TocilizumabIV 
  • IV: 10-12mg/kg for body weight <30kg; 8mg/kg(max 800mg/dose) for body weight >30 kg every4 weeks; may increase frequency to every 2 weeks
  • SC 162mg/dose for body weight <30kg every 3weeks; 162mg/dose for body weight >30 kgevery 2 weeks; may increase frequency to every week

This exercise and CTPs did not consider whether bDMARDs may be appropriate as initial treatment for JDM. 

While Janus kinase (JAK) inhibitors are increasingly used to treat refractory JDM, this class of therapy was not considered, but awaits further research and study.