Rituximab for the treatment of juvenile dermatomyositis: A report of four pediatric patients

Abstract

Objective. Juvenile dermatomyositis (DM) is a chronic inflammatory myopathy of childhood primarily affecting the muscles and skin. Treatment for juvenile DM is often difficult, and conventional therapies include corticosteroids and other immune suppressants. We reviewed the records of 4 patients with juvenile DM who received the B cell-depleting anti-CD20 monoclonal antibody rituximab to determine whether this therapy resulted in improved control of their juvenile DM.Methods. This is a retrospective review of 4 pediatric patients ages 10-17 years with juvenile DM who were treated with rituximab. All patients were tested for myositis autoantibodies and received weekly rituximab infusions for a total of 4 doses. Two patients received repeat courses of rituximab 1 year after their first dose. Patients were followed up between 12 and 24 months after their first course of rituximab, and their strength, muscle enzymes, and rash were reviewed.Results. One patient was positive for a myositisspecific antibody, anti-Mi-2, and demonstrated striking reductions in her muscle enzyme levels for 1 year after rituximab therapy. Following a second course of rituximab, this patient remained disease free for 14 months before requiring a third course of rituximab. Two myositis antibody-negative patients showed clinical improvement and tolerated lower doses of corticosteroids following treatment with rituximab. Finally, 1 patient had worsening of her disease following rituximab.Conclusion. These cases highlight the potential for anti-B cell therapies in the treatment of juvenile DM in both myositis-specific autoantibody-positive and -negative patients.

Extranodal lymphoid microstructures in inflamed muscle and disease severity of new‐onset juvenile dermatomyositis

“…It could be that these structures represent inflammatory foci that are more difficult to disrupt; hence our observation that patients having these structures required additional therapeutic agents. Thus, it will be of interest to examine whether indications of clinical improvement in difficultto-treat juvenile DM with anti-B cell therapy using rituximab (48,49) might involve disruption of the folliclelike structures via the in situ depletion of B cells. Having identified the cellular and molecular components of these extranodal structures, we suggest that they are potential targets of improved immune-based therapies especially for juvenile DM.…”

The Ectopic Germinal Centre Response in Autoimmune Disease and Cancer

“…Some patients relapsed as their B-cell pools repopulated and depletion of autoantibody titres was variable (Chung, Genovese, & Fiorentino, 2007;Cooper et al, 2007;Levine, 2005). The potential of B-cells as therapeutic targets is further supported by the elevations in serum levels and gene expression of B-cell activating factor (BAFF) in IM patients, a cytokine crucial for B-cell maturation and survival, which is also thought to play a role in autoantibody production (Krystufkova et al, 2008;Salajegheh et al, 2010).…”

Immunotherapies for Immune-Mediated Myopathies: A Current Perspective

“…There have also been many positive reports on the efficacy of rituximab in treatment-resistant DM [63][64][65][66][67]. These early reports led to an open-label study of rituximab for refractory PM [68].…”