Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Language English Country England, Great Britain Media electronic
Document type Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't
PubMed
38233885
PubMed Central
PMC10792872
DOI
10.1186/s13075-023-03232-2
PII: 10.1186/s13075-023-03232-2
Knihovny.cz E-resources
- Keywords
- Dermatomyositis, Intravenous immunoglobulin, Myositis, Safety, Tolerability,
- MeSH
- Dermatomyositis * drug therapy MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Immunoglobulins, Intravenous adverse effects MeSH
- Infusions, Intravenous MeSH
- Humans MeSH
- Myositis * chemically induced MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Immunoglobulins, Intravenous MeSH
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).
Department of Dermatology and Allergology University of Szeged Szeged Hungary
Department of Neurology University of Kansas Medical Center Kansas City KS USA
Division of Clinical Immunology Faculty of Medicine University of Debrecen Debrecen Hungary
Division of Rheumatology Medical College of Georgia at Augusta University Augusta GA USA
Octapharma Pharmazeutika Produktionsges m b H Vienna Austria
Phoenix Neurological Associates Ltd Phoenix AZ USA
Tareev Clinic of Internal Diseases Sechenov 1st Moscow State Medical University Moscow Russia
See more in PubMed
Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734–1747. doi: 10.1056/NEJMra1402225. PubMed DOI
Orphanet. Dermatomyositis. Last updated February 2021. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=221.
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. PubMed DOI PMC
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
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. PubMed DOI
Nuno-Nuno L, Joven BE, Carreira PE, Maldonado-Romero V, Larena-Grijalba C, Cubas IL, et al. Mortality and prognostic factors in idiopathic inflammatory myositis: a retrospective analysis of a large multicenter cohort of Spain. Rheumatol Int. 2017;37(11):1853–1861. doi: 10.1007/s00296-017-3799-x. PubMed DOI
Ballow M. The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol. 2011;127(2):315–323. doi: 10.1016/j.jaci.2010.10.030. PubMed DOI
Sewell WA, Jolles S. Immunomodulatory action of intravenous immunoglobulin. Immunology. 2002;107(4):387–393. doi: 10.1046/j.1365-2567.2002.01545.x. PubMed DOI PMC
Elovaara I, Apostolski S, van Doorn P, Gilhus NE, Hietaharju A, Honkaniemi J, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol. 2008;15(9):893–908. doi: 10.1111/j.1468-1331.2008.02246.x. PubMed DOI
Enk A. Guidelines on the use of high-dose intravenous immunoglobulin in dermatology. Eur J Dermatol. 2009;19(1):90–98. doi: 10.1684/ejd.2008.0580. PubMed DOI
Danieli MG, Calcabrini L, Calabrese V, Marchetti A, Logullo F, Gabrielli A. Intravenous immunoglobulin as add on treatment with mycophenolate mofetil in severe myositis. Autoimmun Rev. 2009;9(2):124–127. doi: 10.1016/j.autrev.2009.04.003. PubMed DOI
Aggarwal R, Charles-Schoeman C, Schessl J, Bata-Csörgő Z, Dimachkie MM, Griger Z, et al. Trial of intravenous immunoglobulin in dermatomyositis. New Eng J Med. 2022;387:1264–1278. doi: 10.1056/NEJMoa2117912. PubMed DOI
Aggarwal R, Charles-Schoeman C, Schessl J, Dimachkie MM, Beckmann I, Levine T. Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis (“ProDERM study”) Medicine (Baltimore) 2021;100(1):e23677. doi: 10.1097/MD.0000000000023677. PubMed DOI PMC
OCTAGAM 10%, solution for infusion [19 November 2021]. Available from: https://www.medicines.org.uk/emc/product/4701/smpc#PRODUCTINFO.
OCTAGAM 10% [immune globulin intravenous (human)] liquid solution for intravenous administration [19 November 2021]. Available from: https://www.fda.gov/media/70911/download.
Octagam® product monograph. Octapharma Pharmazeutika Produktionsges, m.b.H. Revised May 6, 2022. Available from: https://pdf.hres.ca/dpd_pm/00065990.PDF.
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) N Engl J Med. 1975;292(7):344–347. doi: 10.1056/NEJM197502132920706. PubMed DOI
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts) N Engl J Med. 1975;292(8):403–407. doi: 10.1056/NEJM197502202920807. PubMed DOI
Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65(2):314–324. doi: 10.1002/art.37754. PubMed DOI PMC
Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349(13):1227–1235. doi: 10.1056/NEJMoa023153. PubMed DOI
National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Clinical guideline (CG144); published 27 June 2012. Available from: https://www.nice.org.uk/guidance/cg144.
Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;329(27):1993–2000. doi: 10.1056/NEJM199312303292704. PubMed DOI
Sansome A, Dubowitz V. Intravenous immunoglobulin in juvenile dermatomyositis–four year review of nine cases. Arch Dis Child. 1995;72(1):25–28. doi: 10.1136/adc.72.1.25. PubMed DOI PMC
Danieli MG, Malcangi G, Palmieri C, Logullo F, Salvi A, Piani M, et al. Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis. Ann Rheum Dis. 2002;61(1):37–41. doi: 10.1136/ard.61.1.37. PubMed DOI PMC
Lim J, Eftimov F, Verhamme C, Brusse E, Hoogendijk JE, Saris CGJ, et al. Intravenous immunoglobulins as first-line treatment in idiopathic inflammatory myopathies: a pilot study. Rheumatology (Oxford) 2021;60(4):1784–1792. doi: 10.1093/rheumatology/keaa459. PubMed DOI PMC
Miyasaka N, Hara M, Koike T, Saito E, Yamada M, Tanaka Y. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial. Mod Rheumatol. 2012;22(3):382–393. doi: 10.3109/s10165-011-0534-4. PubMed DOI PMC
Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;9:1299. doi: 10.3389/fimmu.2018.01299. PubMed DOI PMC
Waheed W, Ayer GA, Jadoo CL, Badger GJ, Aboukhatwa M, Brannagan TH, 3rd, et al. Safety of intravenous immune globulin in an outpatient setting for patients with neuromuscular disease. Muscle Nerve. 2019;60(5):528–537. doi: 10.1002/mus.26678. PubMed DOI
Ammann EM, Jones MP, Link BK, Carnahan RM, Winiecki SK, Torner JC, et al. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy. Blood. 2016;127(2):200–207. doi: 10.1182/blood-2015-05-647552. PubMed DOI PMC
Palabrica FR, Kwong SL, Padua FR. Adverse events of intravenous immunoglobulin infusions: a ten-year retrospective study. Asia Pac Allergy. 2013;3(4):249–256. doi: 10.5415/apallergy.2013.3.4.249. PubMed DOI PMC
Frenzel W, Wietek S, Svae TE, Debes A, Svorc D. Tolerability and safety of Octagam(R) (IVIG): a post-authorization safety analysis of four non-interventional phase IV trials Int J Clin Pharmacol Ther. 2016;54(11):847–55. PubMed PMC
Wietek S. Octagam((R)) for chronic inflammatory demyelinating polyneuropathy: results from three observational studies. Neurodegener Dis Manag. 2018;8(4):227–231. doi: 10.2217/nmt-2018-0006. PubMed DOI PMC
Wietek S, Svorc D, Debes A, Svae TE. Tolerability and safety of the intravenous immunoglobulin octagam((R)) 10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials. Hematology. 2018;23(4):242–247. doi: 10.1080/10245332.2017.1385892. PubMed DOI
Rotrosen ET, Zahedi Niaki O, Kassamali B, et al. Intravenous immunoglobulin and dermatomyositis-associated venous thromboembolism. JAMA Dermatol. 2023;159(6):666–667. doi: 10.1001/jamadermatol.2023.1105. PubMed DOI PMC
Kapoor M, Hunt I, Spillane J, Bonnett LJ, Hutton EJ, McFadyen J, et al. IVIg-exposure and thromboembolic event risk: findings from the UK Biobank. J Neurol Neurosurg Psychiatry. 2022;93(8):876–885. doi: 10.1136/jnnp-2022-328881. PubMed DOI
Xu J, Lupu F, Esmon CT. Inflammation, innate immunity and blood coagulation. Hamostaseologie. 2010;30(1):5–6, 8–9. PubMed
Carruthers EC, Choi HK, Sayre EC, Aviña-Zubieta JA. Risk of deep venous thrombosis and pulmonary embolism in individuals with polymyositis and dermatomyositis: a general population-based study. Ann Rheum Dis. 2016;75(1):110–116. doi: 10.1136/annrheumdis-2014-205800. PubMed DOI PMC
Chung WS, Lin CL, Sung FC, Lu CC, Kao CH. Increased risk of venous thromboembolism in patients with dermatomyositis/polymyositis: a nationwide cohort study. Thromb Res. 2014;134(3):622–626. doi: 10.1016/j.thromres.2014.06.021. PubMed DOI
Gaitonde SD, Ballou SP. Deep venous thrombosis in dermatomyositis. J Rheumatol. 2008;35(11):2288. doi: 10.3899/jrheum.080478. PubMed DOI
Antovic A, Notarnicola A, Svensson J, Lundberg IE, Holmqvist M. Venous thromboembolic events in idiopathic inflammatory myopathy: occurrence and relation to disease onset. Arthritis Care Res (Hoboken) 2018;70(12):1849–1855. doi: 10.1002/acr.23560. PubMed DOI
ClinicalTrials.gov
NCT02728752
