Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis (“ProDERM Study”)

Abstract

Introduction: Dermatomyositis (DM) is an inflammatory myopathy characterized by distinct skin manifestations and muscle weakness. Intravenous immunoglobulin (IVIg) has been used off-label as adjuvant therapy in DM, but is not indicated for DM, due to lack of proven efficacy in a large randomized controlled trial. The objective of the ProDERM (Progress in DERMatomyositis) study was to evaluate the efficacy, safety and long-term tolerability of IVIg (Octagam 10%) in patients with DM in a randomized, placebo-controlled, double-blind, Phase III study. Methods: Adult patients with active DM who were continuing standard therapy at a stable dose were eligible for this study. Patients were randomized 1:1 to receive either 2 g/kg of IVIg or placebo, administered every 4 weeks until week 16 (First Period). Patients were switched to the alternate treatment if they showed clinical deterioration in the First Period. After response assessment at week 16, all patients on placebo and those without deterioration on IVIg entered the open-label Extension Period, receiving 2 g/kg IVIg every 4 weeks for 24 weeks. Results: The primary efficacy endpoint was the proportion of responders in the IVIg vs placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis Response Criteria of at least minimal improvement [Total Improvement Score (TIS) ≥20] and without deterioration at 2 consecutive visits up to week 16. TIS consists of composite response criteria, combining weighted improvement in 6 core set measures (CSMs), Global Disease Activity (Physician and Patient), manual muscle testing-8 (MMT-8), Health Assessment Questionnaire, extra-muscular disease activity, and muscle enzymes. Secondary endpoints included the mean change in individual CSMs, time to improvement in TIS, time to confirmed deterioration in the First Period, and the overall proportion of patients with deteriorations. Adverse events, including infusion reactions and thromboembolic events, were recorded. Conclusions: The ProDERM study was the first to assess the long-term efficacy and safety of IVIg (Octagam 10%) in a placebo-controlled, blinded, randomized trial in DM. The study aimed to inform on the use of IVIg in the treatment of DM, and results are expected in Q3 2020. ClinicalTrials.gov Identifier: NCT02728752.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy

“…Clinical benefit corresponded to significant improvement in muscle cytoarchitecture, increased muscle fiber diameter, reduction of inflammation, revascularization, interception of complement deposition, and downregulation of inflammatory mediators at the protein, mRNA, and gene level [46,47,53,57]. A new large-scale randomized, placebo controlled, phase III study (ProDERM: Progress in DERMatomyositis) evaluating the efficacy and long-term tolerability of IVIg (Octagam 10%) up to 16 weeks with a 24-week extension phase has been now completed [115] and led, as of July 15, to FDA approval for this brand of IVIg for dermatomyositis [FDA orphan drug approval-Octapharma's Octagam 10% receives 7 years of market exclusivity for adult dermatomyositis. Octapharma AG.…”

Dermatologische Differentialdiagnosen von idiopathischen entzündlichen Muskelerkrankungen

“…Von den zur Behandlung der Myositis eingesetzten Wirkstoffen ist für folgende eine Wirksamkeit auch gegen die Hauterscheinungen nachgewiesen worden: Glukokortikoide, Methotrexat [13], IVIG [14,15], Mycophenolatmofetil [16], Rituximab [17] und Stammzelltransplantation [18]. Azathioprin kann zwar eine Wirk-▶abb.…”

Evaluation of Intravenous Immunoglobulin G treatment in Outpatients Rheumatology Practice

“…In some cases, the specific mechanisms of these autoimmune processes are still not elucidated [1]. IVIg has a featured role as an immunomodulatory and anti-inflammatory agent, mostly used "off-label", in autoimmune rheumatic diseases (ARD), except immunodeficiency and dermatomyositis [2,3]. In some small studies have shown the efficacy of IVIg in diverse ARD such as dermatomyositis/polymyositis (DM/PM), systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) [2,[4][5][6].…”

“…IVIg has a featured role as an immunomodulatory and anti-inflammatory agent, mostly used "off-label", in autoimmune rheumatic diseases (ARD), except immunodeficiency and dermatomyositis [2,3]. In some small studies have shown the efficacy of IVIg in diverse ARD such as dermatomyositis/polymyositis (DM/PM), systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) [2,[4][5][6]. IVIg is generally considered a safe therapy, and most of the side effects are mild and may be ameliorated with slower rates of infusion, premedication, and hydration [7][8][9].…”