Intravenous immunoglobulins as first-line treatment in idiopathic inflammatory myopathies: a pilot study

Abstract

Objectives: We explored efficacy and safety of IVIg as first-line treatment in patients with an idiopathic inflammatory myopathy.

Methods: In this investigator-initiated phase 2 open-label study, we included 20 adults with a newly diagnosed, biopsy-proven idiopathic inflammatory myopathy, and a disease duration of less than 9 months. Patients with IBM and prior use of immunosuppressants were excluded. The standard treatment regimen consisted of IVIg (Privigen) monotherapy for 9 weeks: a loading dose (2 g/kg body weight) and two subsequent maintenance doses (1 g/kg body weight) with a 3-week interval. The primary outcome was the number of patients with at least moderate improvement on the 2016 ACR/EULAR Total Improvement Score. Secondary outcomes included time to improvement, the number of patients requiring rescue medication and serious adverse events.

Results: We included patients with DM (n = 9), immune-mediated necrotizing myopathy (n = 6), non-specific myositis/overlap myositis (n = 4) and anti-synthetase syndrome (n = 1). One patient was excluded from analyses because of minimal weakness resulting in a ceiling effect. Eight patients (8/19 = 42.0%; Clopper-Pearson 95% CI: 19.6, 64.6) had at least moderate improvement by 9 weeks. Of these, six reached improvement by 3 weeks. Seven patients required rescue medication due to insufficient efficacy and prematurely ended the study. Three serious adverse events occurred, of which one was pulmonary embolism.

Conclusion: First-line IVIg monotherapy led to at least moderate improvement in nearly half of patients with a fast clinical response in the majority of responders.

Trial registration: Netherlands Trial Register identifier, NTR6160.

Keywords: immunotherapy; myositis and muscle disease.

Fig. 1

Study treatments (A) Patients received a 2 g/kg BW loading dose of IVIg monotherapy at baseline and thereafter two 1 g/kg BW follow-up infusions every 3 weeks. (B) Patients were converted to IVIg 2 g/kg BW every 4 weeks in cases of insufficient response by week 4 defined as a Total Improvement Score of <40. The patients continued treatment after 9 weeks at the discretion of the treating physician. BW: body weight.

Fig. 2

Schematic representation of screening and inclusion of patients Note that patients may have more than one reason to be non-eligible.

Fig. 3

Treatment response of the 19 included patients in the analysis Treatment response was assessed by the 2016 ACR/EULAR TIS. Improvement was defined as a TIS of at least 40 by 9 weeks of IVIg treatment (dotted red line). Eight patients reached at least moderate improvement by 9 weeks of treatment (A), while 11 patients did not (B). TIS: Total Improvement Score.