A First Step in Precision Neurology?
The present study “provides initial data that preemptive strategies may allow for a more consistent approach to safely administer this commonly used medication,” said Yijing He, MD, PhD; Lucia Seminario-Vidal, MD, PhD; and Howard L. McLeod, PharmD, in an accompanying editorial. A substantial decrease in the incidence and severity of carbamazepine-associated cutaneous adverse drug reactions was documented. While the study did not have the statistical power to definitively demonstrate complete avoidance of the high-morbidity and -mortality forms of severe cutaneous adverse drug reactions (ie, Stevens-Johnson syndrome and toxic epidermal necrolysis), it had statistical power to detect an important reduction in mild or moderately severe forms of cutaneous adverse drug reactions.
“However, 23 patients experienced a carbamazepine-associated cutaneous adverse drug reaction,” and four patients required hospitalization, the editorialists noted. “Therefore, the use of HLA-A*31:01 testing will not eliminate the risk of carbamazepine-associated events, nor will it decrease the need for neurologists to provide skin-focused monitoring as part of their management of cases involving carbamazepine-treated patients.”
This research, the editorialists said, indicates that there is still more to discover. “To date, a small number of heroes has relentlessly pursued mechanistic and preventive research on drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. However, the field needs to build on these efforts with a more systematic approach that will aid more rapid progress and provide more consistent influence across the globe.” Much still needs to be learned about the basic mechanisms, clinical confounders, biomarkers, and epidemiologic aspects of the various drug reactions that become Stevens-Johnson syndrome and toxic epidermal necrolysis. Attributing this clinical, immunologic, and therapeutic problem to various idiosyncratic reactions does not serve patients well, said the editorialists.
A key first step, the editorialists said, is to “apply existing preemptive strategies, including genomic analysis. Whether this is initially implemented broadly or in regions with higher probability of the risk alleles is less important than learning how to change a culture that tolerates adverse drug events and inventing informatics tools to make proactive approaches less of a burden. Although we will not get it completely right the first time, we need to start the iterative process to eradicate severe cutaneous adverse drug reactions.”
