Naohiro Sakamoto

In this study, blood cell counts and serum C3, C4, and CH50 values at baseline and after more than 6-month drug use were measured to elucidate changes in blood cells and complements during relapse prevention therapies for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD). A total of 70 patients with AQP4+ NMOSD (87% female, median age 56 years) were enrolled. They were divided into the following treatment groups: glucocorticoids and/or immunosuppressants (GC/IS, n = 22), inebilizumab/rituximab (anti-CD19/20, n = 13), satralizumab (anti-IL-6R, n = 22), and eculizumab/ravulizumab (anti-C5, n = 13). At baseline, the blood counts and complement levels did not differ among the groups. At follow-up, the neutrophil and platelet counts in the anti-IL-6R group decreased from those at baseline (p < 0.0001 and p < 0.001, respectively). Compared with the GC/IS, anti-CD19/20, and anti-C5 groups, the anti-IL-6R group had lower levels of C3 (p < 0.0001, p < 0.01, and p < 0.05, respectively) and C4 (p < 0.0001, p < 0.01, p < 0.001, respectively). Furthermore, the anti-C5 group had significantly lower CH50 levels than the GC/IS, anti-CD19/20, and anti-IL-6R groups (p < 0.0001, p < 0.0001, p < 0.05, respectively). In addition, the anti-IL-6R group had lower CH50 levels than the GC/IS and anti-CD19/20 groups (p < 0.001 and p < 0.05, respectively). The present study demonstrated that anti-IL-6R therapy broadly and mildly suppressed the complement system and decreased the neutrophil and platelet counts. It also showed that anti-C5 therapy strongly suppressed total complement activity but did not affect the C3 and C4 levels or blood counts. These findings may have implications for the mode of action of the drugs and the risk of adverse drug reactions, including infections.

Introduction: Mixed connective tissue disease (MCTD) patients often have myositis, however, myopathological and clinical data for MCTD are limited. Recent reports have shown that the pathology of MCTD myositis resembles that of immune‐mediated necrotizing myopathy (IMNM), whereas earlier reports described perifascicular atrophy or inflammatory infiltrates predominantly in the perivascular region in MCTD myositis. We aim to describe the clinical and myopathological features of MCTD myositis.Methods: We analyzed the clinical and myopathological findings of nine myositis patients with U1‐RNP antibodies who fulfilled the diagnostic criteria for MCTD.Results: Eight patients had muscle weakness in the proximal extremities, and overall, six patients had atypical weakness in the face, neck, wrist, or fingers. Four of those patients required additional intensive treatment (intravenous immunoglobulin or methylprednisolone). Therapeutic responses were consistently favorable overall, and there were no deaths during the observation period. In biopsied muscle specimens, common findings were mild myogenic change, increased necrotic and regenerating fibers, and inflammatory infiltrates predominating in the perivascular region. Two specimens were classified into the spectrum of dermatomyositis (DM); the remaining seven specimens, which had a smaller number of necrotic fibers and nonspecific infiltration, were unclassifiable.Discussion: Patients with MCTD myositis often exhibit an axial or atypical distribution of muscle weakness, which may require intensive therapy. Histological study demonstrates the heterogeneity of myopathology of MCTD myositis and suggests that DM and underlying vasculopathy might be present in these patients.