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Clinical Trial
. 2024 Jan 17;26(1):27.
doi: 10.1186/s13075-023-03232-2.

Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study

Rohit Aggarwal  1 , Joachim Schessl #  2 , Christina Charles-Schoeman #  3 , Zsuzsanna Bata-Csörgő  4 , Mazen M Dimachkie  5 , Zoltan Griger  6 , Sergey Moiseev  7 , Chester V Oddis  8 , Elena Schiopu  9 , Jiri Vencovský  10 , Irene Beckmann  11 , Elisabeth Clodi  11 , Todd Levine  12 ; ProDERM investigators
Affiliations
Clinical Trial

Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study

Rohit Aggarwal et al. Arthritis Res Ther. .

Abstract

Background: Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study.

Methods: ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0-16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16-40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented.

Results: The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4-15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred.

Conclusions: Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors.

Trial registration: ProDERM study (NCT02728752).

Keywords: Dermatomyositis; Intravenous immunoglobulin; Myositis; Safety; Tolerability.

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Conflict of interest statement

RA has received grants or contracts from Mallinckrodt, Pfizer, Bristol Myers-Squibb, Boehringer Ingelheim, Q32, EMD Serono and Janssen; and consulting fees from Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, Alexion, Boehringer Ingelheim, Janssen, Roivant, Galapagos, Abbvie, Horizontal Therapeutics, Biogen, ANI Pharmaceutical, Capella, Ililli, Medicxi, EMD Serono, Kezar, Pfizer, Astra Zeneca, Argenx, Corbus, Kyverna, Merck, Actigraph, Scipher, Teva, Beigene, Nuvig, Cabaletta Bio and Sanofi. JS has received support for the current manuscript and funding and consultancy fees from Octapharma; and honoraria for presentations, from Pfizer. CC-S has received grants or contracts from Pfizer, Bristol Myers Squibb, Abbvie, CSL Behring, Alexion and Priovant; consulting fees from Pfizer, Bristol Myers Squibb, Abbvie, Octapharma, Priovant, Galapagos, Recludix and Boehringer Ingelheim Pharmaceuticals; and participated on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb. ZB-C has received payment or honoraria for lectures from Sanofi, Berlin-Chemie and Abbvie; support for attending meetings from Sanofi and Biotest AG; and unpaid board membership in the Hungarian Dermatology and Immunology and Allergy Societies. MMD has received grants or contracts from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, The Myositis Association, UCB Biopharma/RaPharma, Viromed/Healixmith and TMA; consultancy fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and participated on a Data Safety Monitoring Board or Advisory Board for Abcuro, Amazentis, ArgenX, Astellas, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, MDA, Medlink, Momenta, NuFactor, Octapharma, Priovant, RaPharma/UCB, Roivant Sciences Inc, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Abata/Third Rock and UCB Biopharma; and received royalty fees or licenses, consultancy fees, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from UpToDate. ZG has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Lilly, Novartis, Roche; received support for attending meetings and/or travel from Biotest, CSL Behring, Novartis, Abbvie and Lilly; and participated on a Data Safety Monitoring Board or Advisory Board for Octapharma. CVO has received research support from Genentech and consulting fees from Pfizer. JV has received support for the current manuscript from the Czech Ministry of Health; grants or contracts from Abbvie; consulting fees from Argenx; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Werfen and Octapharma; and Participated on a Data Safety Monitoring Board or Advisory Board for Horizon, Kezar, Boehringer and Octapharma. IB was an employee of Octapharma Pharmazeutika Produktionsges.m.b.H until June 2022; and has subsequently received Consulting fees from Octapharma. EC is an employee of Octapharma Pharmazeutika Produktionsges.m.b.H. TL is a consultant for FFF Enterprises. SM and ES have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Study design. X, drop-out. *CD, confirmed deterioration. Defined as change from baseline on two consecutive visits in Physician’s Global Disease Activity VAS worsening ≥ 2 cm and MMT-8 worsening ≥ 20%, OR global extra-muscular activity worsening ≥ 2 cm on the MDAAT VAS, OR any three of five CSM (core set measures, excluding enzymes) worsening by ≥ 30%). **Physician’s Global Disease Activity (GDA) value of 0–3 (mild), 4–6 (moderate), 7–10 (major). #Placebo patients having confirmed deterioration at week 16 continued in open-label part
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References

    1. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734–1747. doi: 10.1056/NEJMra1402225. - DOI - PubMed
    1. Orphanet. Dermatomyositis. Last updated February 2021. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=221.
    1. Kronzer VL, Kimbrough BA, Crowson CS, Davis JM, 3rd, Holmqvist M, Ernste FC. Incidence, prevalence, and mortality of dermatomyositis: a population-based cohort study. Arthritis Care Res (Hoboken) 2023;75(2):348–355. doi: 10.1002/acr.24786. - DOI - PMC - PubMed
    1. Qudsiya Z, Waseem M. Dermatomyositis. [Updated 2023 Aug 7]. In: StatPearls. Treasure Island: StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558917/. - PubMed
    1. Muhammed H, Gupta L, Zanwar AA, Misra DP, Lawrence A, Agarwal V, et al. Infections are leading cause of in-hospital mortality in Indian patients with inflammatory myopathy. J Clin Rheumatol. 2021;27(3):114–119. doi: 10.1097/RHU.0000000000001214. - DOI - PubMed

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