Precision Medicine and immunomodulatory therapy for Stevens Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a rare but fatal immune-mediated Severe Cutaneous Adverse Reaction (SCAR) which is often drug-induced frequently involving the eyes leading to corneal blindness.... [ view full abstract ]

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a rare but fatal immune-mediated Severe Cutaneous Adverse Reaction (SCAR) which is often drug-induced frequently involving the eyes leading to corneal blindness. The pathophysiology is not completely understood and despite symptomatic treatment involving a multidisciplinary approach there is significant morbidity and mortality. The survivors most often have long-term ocular sequelae.  Given the natural history of SJS/TEN and involvement of various Human Leucocyte Antigen (HLA) genes affecting different ethnic groups globally, conducting a multi-centric clinical trial with required optimum number of subjects could be quite a challenge.  Patient registries provide useful data but may be difficult or impossible to control for confounding variables and bias.  However, lack of adequate patient registries as in SJS/TEN may pose additional problems.  Given that this condition is drug-induced with more than 200 drugs known to be serious culprits, the existing and future drug pipelines are warranted to undergo cheminformatics-aided pharmacovigilance in order to control the incidence of SJS/TEN.   Although HLA genes are associated with this condition together with specific culprit drugs, but identification of how the HLA genes interact with the drug in the host system is of paramount importance in disease prevention, and earlier diagnosis in order to have a strategic multidisciplinary approach in its treatment.  With the advent of Precision Medicine, newer study designs pertaining to randomized clinical trials for rare diseases have to be established and technological advances such as exome sequencing used in order to achieve tangible clinical outcomes.  It is crucial to carefully map the genomic landscape of rare diseases like SJS/TEN in order to assess the response to combination immunomodulatory therapy.   Although some of the currently available immune check point inhibitors may trigger SJS/TEN as adverse effects, a careful designing of immunomodulatory drugs is warranted.   This presentation will provide a unique blend of discussions on the challenges of clinical trials on rare diseases in general and SJS/TEN in particular combined with the clinical manifestations of this rare condition and the potential role of selective immunomodulatory therapy.