Clinical trial of TNF-α antagonist for severe cutaneous adverse reactions uses the NovoCyte®

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCARs) involving keratinocyte apoptosis and detachment of the epidermis. Current treatments, which include the use of corticosteroids, are controversial in their effectiveness. Numerous studies have demonstrated that the mechanism of SJS-TEN involves effector cytotoxic T lymphocytes (CTLs). In addition, treatment with anti–TNF-α biologic agents appears to be beneficial in patients with TEN and TEN-like acute cutaneous lupus erythematosus. However a randomized, systemic trial had not yet been run. 

Investigators Wang et al. address this issue in a clinical trial published in a current issue of the Journal of Clinical investigation. The authors concluded that the anti–TNF-α biologic agent etanercept is an effective alternative treatment for CTL-mediated SCARs. In comparison with conventional systemic corticosteroids, etanercept showed a shorter skin-healing time for patients with moderate-to-severe CTL-mediated SCARs, with a lower incidence of GI side effects. 

In the article, the researchers used the NovoCyte flow cytometer from ACEA Biosciences to determine the frequency of regulatory T cells (Treg cells) in patients after treatment with either Etanercept or Corticosteroid (Figure below). Treg cells (identified as CD4+CD25hiFoxp3+) were measured in patient’s blood at various stages of the illness. It was determined that entanercept but not corticosteroid treatment increased Treg cell populations, identifying a possible mechanism of action by which entabercept may help ameliorate the disease. In conclusion, this study may provide a rationale for the clinical application of anti–TNF-α biologic agents in the treatment of patients with CTL-mediated SCARs.

Immunological effects in SJS-TEN patients with 10% or greater BSA detachment after etanercept or corticosteroid treatment. Figures adapted from J Clin Invest. 2018 Feb 5. pii: 93349. doi: 10.1172/JCI93349.