Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 19;26(9):107670.
doi: 10.1016/j.isci.2023.107670. eCollection 2023 Sep 15.

A randomized clinical trial of bermekimab treatment for clinical improvement of systemic sclerosis

Affiliations

A randomized clinical trial of bermekimab treatment for clinical improvement of systemic sclerosis

Nicky Solomonidi et al. iScience. .

Abstract

Increased concentrations of interleukin (IL)-1α have been recently described in tissues of patients with systemic sclerosis (SSc) suggesting that IL-1α inhibition may be a target for treatment. We conducted a double-blind, placebo-controlled study to assess the safety and efficacy of the fully humanized IL-1α blocking monoclonal antibody bermekimab in SSc. To evaluate response to treatment, we developed the score of inhibition of progression of SSc which was validated using the CRISS index and the modified CRISS index. The primary endpoint was met in 80% of bermekimab-treated patients vs. 20% of placebo-treated patients (p: 0.023). Most of efficacy was found for increase of carbon monoxide lung diffusion capacity. Production of IL-1α and TNF by circulating mononuclear cells was decreased and the absolute count of CD42/Cd62-platelets was decreased. Results suggest that bermekimab is a promising treatment for SSc.

Keywords: Health sciences; Medicine; Neurology; Pharmacology.

PubMed Disclaimer

Conflict of interest statement

E.J.G.B. has received honoraria from Abbott Products Operations AG, bioMérieux Inc, Brahms GmbH, GSK, InflaRx GmbH, Sobi AB and UCB; independent educational grants from Abbott Products Operation AG, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi AB and UCB.; and funding from the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and from the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). The other authors do not have any competing interest to declare.

Figures

None
Graphical abstract
Figure 1
Figure 1
The LIGHT trial (see also Table S2) (A) Study flow chart. (B) Study design. Abbreviations DLCO: carbon monoxide diffusion capacity; FVC: forced vital capacity; ITT: intent-to-treat; mRSS, modified Rodnan skin score; NCM: nailfold capillaromiscroscopy; SSc: systemic sclerosis; SF-36: Short Form 36; VAS: visual analogue scale; wk: week.
Figure 2
Figure 2
Main biomarker changes following treatment with bermekimab (see also Figure S2) (A and B) Changes of the absolute counts of CD42/CD62 activated platelets over treatment. Panel A shows the absolute counts of CD42/CD62 activated platelets at baseline week 0. Panel B shows the relative changes of the absolute counts of CD42/CD62 activated platelets between patients treated with placebo for 12 weeks, patients treated with bermekimab for 12 weeks and patients treated with bermekimab for 24 weeks. p values of the indicated comparisons are shown. (C and D) Changes of the circulating concentrations of vascular endothelial growth factor (VEGF) over treatment. Panel C shows the concentrations of circulating VEGF at baseline week 0. Panel D shows the relative changes of circulating VEGF between patients treated with placebo for 12 weeks, patients treated with bermekimab for 12 weeks and patients treated with bermekimab for 24 weeks. p values of the indicated comparisons are shown. (E and F) Changes of the circulating concentrations of tumor necrosis factor (TNF) over treatment. Panel E shows the concentrations of cirulating TNF at baseline week 0. Panel D shows the relative changes of circulating TNF between patients treated with placebo for 12 weeks, patients treated with bermekimab for 12 weeks and patients treated with bermekimab for 24 weeks. p values of the indicated comparisons are shown. Abbreviations n: number of patients; wk: weeks.
Figure 3
Figure 3
Cytokine production from circulating peripheral blood mononuclear cells (PBMCs) at week 12 PBMCs were isolated after 12 weeks from start of treatment with placebo or bermekimab and stimulated by heat-killed Staphylococcus aureus for the production of tumor necrosis factor (TNF), interleukin (IL)-1α and IL-1β. Cytokine production from healthy volunteers (HV) is also provided. p values refer to comparisons indicated by the arrows.

References

    1. Cutolo M., Sulli A., Pizzorni C., Paolino S., Smith V. Systemic sclerosis: markers and targeted treatments. Acta Rheumatol. Port. 2016;41:18–25. - PubMed
    1. Giacomelli R., Liakouli V., Berardicurti O., Ruscitti P., Di Benedetto P., Carubbi F., Guggino G., Di Bartolomeo S., Ciccia F., Triolo G., Cipriani P. Interstitial lung disease in systemic sclerosis: current and future treatment. Rheumatol. Int. 2017;37:853–863. doi: 10.1007/s00296-016-3636-7. - DOI - PubMed
    1. Denton C.P., Engelhart M., Tvede N., Wilson H., Khan K., Shiwen X., Carreira P.E., Diaz Gonzalez F., Black C.M., van den Hoogen F.H. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Ann Rheum. 2009;68:1433–1439. doi: 10.1136/ard.2008.096123. - DOI - PubMed
    1. Charles C., Clements P., Furst D.E. Systemic sclerosis: hypothesis driven treatment strategies. Lancet. 2006;367:1683–1691. doi: 10.1016/S0140-6736(06)68737-0. - DOI - PubMed
    1. Denton C.P. Advances in pathogenesis and treatment of systemic sclerosis. Clin. Med. 2015;15(Suppl 6):58–63. doi: 10.7861/clinmedicine.15-6-s58. - DOI - PubMed

LinkOut - more resources