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

Johan Lim, Filip Eftimov, Camiel Verhamme, Esther Brusse, Jessica E Hoogendijk, Christiaan G J Saris, Joost Raaphorst, Rob J De Haan, Ivo N van Schaik, Eleonora Aronica, Marianne de Visser, Anneke J van der Kooi, Johan Lim, Filip Eftimov, Camiel Verhamme, Esther Brusse, Jessica E Hoogendijk, Christiaan G J Saris, Joost Raaphorst, Rob J De Haan, Ivo N van Schaik, Eleonora Aronica, Marianne de Visser, Anneke J van der Kooi

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.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
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
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
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.

References

    1. Van de Vlekkert J, Hoogendijk JE, de Visser M.. Long-term follow-up of 62 patients with myositis. J Neurol 2014;261:992–8.
    1. Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep 2012;14:275–85.
    1. Van de Vlekkert J, Hoogendijk JE, de Haan RJ. et al. Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial. Neuromuscul Disord 2010;20:382–9.
    1. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA 2004;291:2367–75.
    1. Dalakas MC, Illa I, Dambrosia JM. et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993–2000.
    1. Miyasaka N, Hara M, Koike T. et al. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomised double-blind placebo-controlled trial. Mod Rheumatol 2012;22:382–93.
    1. Moriguchi M, Suzuki T, Tateishi M, Hara M, Kashiwazaki S.. Intravenous immunoglobulin therapy for refractory myositis. Intern Med 1996;35:663–7.
    1. Saito E, Koike T, Hashimoto H. et al. Efficacy of high-dose intravenous immunoglobulin therapy in Japanese patients with steroid-resistant polymyositis and dermatomyositis. Mod Rheumatol 2008;18:34–44.
    1. Cherin P, Piette JC, Wechsler B. et al. Intravenous gamma globulin as first line therapy in polymyositis and dermatomyositis: an open study in 11 adult patients. J Rheumatol 1994;21:1092–7.
    1. Mammen AL, Tiniakou E.. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med 2015;373:1680–2.
    1. Hoogendijk JE, Amato AA, Lecky BR. et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord 2004;14:337–45.
    1. Miller FW, Rider LG, Chung YL. et al. Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies. Rheumatology 2001;40:1262–73.
    1. Isenberg DA, Allen E, Farewell V. et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology 2004;43:49–54.
    1. Lundberg IE, Tjarnlund A, Bottai M. et al. 2017 European League against Rheumatism/American College of Rheumatology Classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Arthritis Rheumatol 2017;69:2271–82.
    1. Mariampillai K, Granger B, Amelin D. et al. Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol 2018;75:1528–37.
    1. Cavazzana I, Fredi M, Ceribelli A. et al. Testing for myositis specific autoantibodies: comparison between line blot and immunoprecipitation assays in 57 myositis sera. J Immunol Methods 2016;433:1–5.
    1. Shovman O, Gilburd B, Chayat C. et al. Anti-HMGCR antibodies demonstrate high diagnostic value in the diagnosis of immune-mediated necrotizing myopathy following statin exposure. Immunol Res 2017;65:276–81.
    1. Hughes RA, Donofrio P, Bril V. et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol 2008;7:136–44.
    1. Aggarwal R, Rider LG, Ruperto N. et al. 2016 American College of Rheumatology/European League against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: an International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol 2017;69:898–910.
    1. Vanhoutte EK, Faber CG, van Nes SI. et al. Modifying the Medical Research Council grading system through Rasch analyses. Brain 2012;135:1639–49.
    1. Baschung Pfister P, de Bruin ED, Sterkele I. et al. Manual muscle testing and hand-held dynamometry in people with inflammatory myopathy: an intra- and interrater reliability and validity study. PLoS One 2018;13:e0194531.
    1. Hillel AD, Miller RM, Yorkston K. et al. Amyotrophic lateral sclerosis severity scale. Neuroepidemiology 1989;8:142–50.
    1. Farrell B, Godwin J, Richards S, Warlow C.. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991;54:1044–54.
    1. Janssen MF, Pickard AS, Golicki D. et al. Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study. Qual Life Res 2013;22:1717–27.
    1. Herdman M, Gudex C, Lloyd A. et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36.
    1. The National Institute of Environmental Health Sciences (NIEHS). IMACS Form 00: Clinical Trial Design Features. (3 October 2016, date last accessed).
    1. Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology 1990;1:43–6.
    1. Cao H, Pan M, Kang Y. et al. Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti-melanoma differentiation-associated gene 5 antibody. Arthritis Care Res 2012;64:1602–10.
    1. Hall JC, Casciola-Rosen L, Samedy LA. et al. Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res 2013;65:1307–15.
    1. Hamaguchi Y, Kuwana M, Hoshino K. et al. Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. Arch Dermatol 2011;147:391–8.
    1. Troyanov Y, Targoff IN, Tremblay JL. et al. Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients. Medicine 2005;84:231–49.
    1. Lim J, Rietveld A, De Bleecker JL. et al. Seronegative patients form a distinctive subgroup of immune-mediated necrotizing myopathy. Neurol Neuroimmunol Neuroinflamm 2019;6:e513.
    1. Shi J, Li S, Yang H. et al. Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies. J Rheumatol 2017;44:1051–7.
    1. Hamaguchi Y, Fujimoto M, Matsushita T. et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One 2013;8:e60442.
    1. Danieli MG, Gelardi C, Pedini V. et al. Subcutaneous immunoglobulin in inflammatory myopathies: efficacy in different organ systems. Autoimmun Rev 2020;19:102426.

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