Systemic Scleroderma

A study is underway which will evaluate the efficacy of bermekimab in systemic sclerosis. The lead investigator of the study is Evangelos J. Giamarellos-Bourboulis, MD, PhD, who conducted the phase 2 randomized clinical study in hidradenitis suppurativa. The single site study will evaluate efficacy of bermekimab treatment in 20 adults with systemic scleroderma. The study will consist of 2 phases; first phase will consist of patients randomized 1:1 to weekly subcutaneous treatment with 400mg bermekimab in pre-filled syringes or matched placebo for 12 weeks. The second will be an open label phase where all patients will receive weekly 400mg subcutaneous bermekimab treatments for an additional 12 weeks.

Systemic sclerosis (SSc also known as scleroderma) is a devastating chronic immune-mediated inflammatory syndrome that is characterized by progressive organ dysfunction. The most common affected systems are the skin, the gastrointestinal tract, the lungs and the heart. Capillary endothelium is involved leading to ischemia and digital necrosis. Patients develop an interstitial lung disease (ILD) prototype dominated by pulmonary hypertension (PHA) and failed gad exchange. Almost all patients are also presenting with signs of intestinal dysmotility leading to gastrointestinal reflux and bloating1. Hallmarks of SSc are fibrosis of the skin and internal organs, production of autoantibodies and vasculopathy. SSc is the only rheumatic disorder accompanied by substantial lethality; so far no specific treatment targeting the mechanism of pathogenesis is available2.

Levels of serum IL-1α have been shown to be significantly higher in SSc patients than in those healthy subjects3. The increased circulating levels of IL-1α in patients with SSc and the role of IL-1α autocrine vicious stimulation of fibroblasts for the production of pre-collagen generate the possibility that targeting IL-1α may be a novel target of SSc treatment. This is a proof-of concept study evaluating whether inhibition of IL-1α through the administration of bermekimab may effectively treat SSc.

Relevant Publication

  • Denton CP, Khanna D, Systemic sclerosis. Lancet 2017; 390: 1685-1699
  • van den Hombergh WMT, Kersten BE, Knaapen-Hans HKA, Thurlings RM, van der Kraan PM, van den Hoogn FHJ, et al. Hit hard and early: analusing the effects of high-dose methylprednisolone on nailfold capillary changes and biomarkers in very early systemic sclerosis: study protocol for a 12-week randomized controlled trials. Trials 2018; 19: 449
  • Maekawa T, Jinnin M, Ohtsuki M, Ihn H. Serum levels of interleukin-1α in patients with systemic sclerosis. J Dermatol. 2013 Feb;40(2):98-101. doi: 10.1111/1346-8138.12011. Epub 2012 Oct 18.