Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study.

Background: Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM.
Methods: ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM 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. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752.
Findings: The study took place from February 2017 to November 2019. 95 patients received IVIg (N = 47) or placebo (N = 48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0 g/kg). At Week 16, mean CDASI-A change from baseline was -9.36 (95% CI: -12.52, -6.19) in the IVIg group versus -1.16 (-3.32, 0.99) in placebo group (p < 0.0001). At the end of the Extension Period, mean changes from baseline were -10.44 (95% CI: -13.94, -6.94) and -10.03 (-13.12, -6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity.
Interpretation: ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM.
Funding: This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.
Competing Interests: VW has received grants from Celgene, Janssen, Pfizer, Biogen, Gilead, Corbus Pharmaceuticals, Genentech, AstraZeneca, Viela, Syntimmune, Amgen, Regeneron, Argenx, CSL Behring, Ventus, q32 Bio, BMS, Horizon, Rome Pharmaceuticals and Priovant; royalties for licenses from the University of Pennsylvania; consulting fees from Celgene, Genentech, Janssen, Lilly, Pfizer, Biogen, BMS, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Sorona, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kwoya Kirin, Regeneron, Principia, AstraZeneca, Abbvie, Octapharma, GSK, Astra-Zeneca, Cugene, UCB, Corcept, Beacon Bioscience, Rome Pharmaceuticals, Horizon, Gilead, Merck, Kezar, Sanofi, Bayer, Akari, Calyx and Cabaletta Bio; and has participated in a Data Safety Monitoring Board or Advisory Board for Astra Zeneca. 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. 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. JS has received support for the current manuscript and consultancy fees from Octapharma; and honoraria for presentations, from Pfizer. TL is a consultant for FFF Enterprises. MW has received consulting fees from Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A., Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc., Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH and GlaxoSmithKline GmbH & Co. KG; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A., Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc., Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH and GlaxoSmithKline GmbH & Co. KG; and participated on a Data Safety Monitoring Board or Advisory Board for Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A., Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc., Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH and GlaxoSmithKline GmbH & Co. KG. 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. NK has no conflicts of interest to declare.
(© 2023 The Authors.)