Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy

Abstract

This open-label, 24-week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).Methods. Ten patients ≥7 years of age with moderate disease activity were enrolled in a 24-week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)-regulated gene score was performed on whole-blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.Results. Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down-trending IFN-regulated gene scores and galectin-9 expression at week 24. Decreases in IFN-regulated gene scores and in levels of interferon-γ-inducible protein 10kDa, galectin-9, and interleukin-2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment-emergent adverse events were observed.Conclusion. This open-label study demonstrated that abatacept may be beneficial for patients with treatment-refractory juvenile DM.

Novel therapeutic targets in dermatomyositis

“…Six patients had downtrending IFN-regulated gene scores and galectin-9 expression at week 24, with decreases in IFN-regulated gene scores and in levels of IFNγ-inducible protein 10 kDa, galectin-9, and IL-2, correlating with muscle edema seen on MRI and overall improvements in disease activity. 16 These changes provide a possible physiological mechanism for abatacept's effect on DM.…”

Juvenile Dermatomyositis und andere idiopathische inflammatorische Myopathien des Kindesalters

“…In einer prospektiven Pilotstudie zeigte Etanercept keine Effektivität bei aktiver JDM [61], wohingegen für Adalimumab und Infliximab zumindest günstige Befunde aus Beobachtungsstudien vorliegen [62]. Abatacept zeigte in einer Open-Label-Studie günstige Ergebnisse bei refraktärer JDM [63].…”

Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care

“…Although TNF inhibitors, particularly adalimumab or infliximab, might be helpful in some patients with JIIM, evidence from a systemic review suggest that treatment with these drugs does not lead to complete remission and better treatments are needed 165 . Abatacept has demonstrated efficacy in a randomized controlled trial in adult onset myositis 179 and in an open label therapeutic trial in JIIM 180 . Abatacept might be helpful for the treatment of resistant disease, including calcinosis 179 , 181 , 182 .…”