To test or not to test: Isotretinoin marginally increases risk for severe adverse events
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Key takeaways:
- Those taking isotretinoin exhibited a 7.85 times increased risk for severe hypertriglyceridemia vs. those taking oral antibiotics.
- They were also 1.45 times more likely to have severely elevated liver enzymes.
Isotretinoin is associated with a clinically marginal increased risk for severe adverse events, leading researchers to advise routine blood testing commence shortly after initiation, according to a study.
Isotretinoin is a mainstay treatment for severe acne as it exhibits “remarkable clinical efficacy and sustained results,” according to Shirin Emtenani, MSc, PhD, a postdoctoral researcher for the Lübeck Institute of Experimental Dermatology at the University of Lübeck in Germany, and colleagues. However, the drug is also associated with various severe adverse events including hypertriglyceridemia, liver enzyme abnormalities, leukopenia and thrombocytopenia.
Current guidelines require patients to be subjected to frequent laboratory monitoring, but many clinicians have challenged the necessity of how often these tests are to be performed.
“A substantial knowledge gap exists regarding the most effective laboratory monitoring routine for acne patients receiving isotretinoin treatment,” Emtenani and colleagues wrote. “Several reports have raised doubts about the clinical value of frequent (eg, baseline testing and/or monthly follow-up) laboratory monitoring and have proposed a reduction in monitoring frequencies.”
In this retrospective study, the authors evaluated the risk for mild and severe abnormal laboratory parameters among patients with acne that are treated with isotretinoin vs. oral antibiotics in an effort to answer whether frequent monitoring is necessary.
The study included two groups, both with 79,012 patients matched for demographic variables and major comorbidities. One group was treated for acne with isotretinoin, whereas the other was treated with oral antibiotics. Researchers evaluated patients’ laboratory results and categorized them as grade 1 or higher, meaning mild risk to health, and grade 3 or higher, meaning severe risk to health.
Results showed that those taking isotretinoin exhibited a 7.85 times (95% CI, 5.58-11.05) increased risk for grade 3 or higher hypertriglyceridemia compared with those taking oral antibiotics within the first 3 months of treatment.
Regarding liver function, isotretinoin-treated patients were also 1.45 times (95% CI, 1.13-1.85) more likely to have grade 3 or higher elevated aspartate transaminase levels vs. antibiotic-treated patients in the same time period.
While isotretinoin-treated patients encountered a higher risk than their antibiotic-treated counterparts, the absolute risk for severe hypertriglyceridemia and elevated aspartate transaminase levels among isotretinoin users was 0.4% and 0.2%, respectively. The clinical difference of these findings was marginal, with three and one respective cases occurring every 1,000 patients starting isotretinoin.
There was no significant risk for severe impairment in cholesterol, alanine transaminase, gamma-glutamyl transferase or creatinine levels during isotretinoin treatment. According to the authors, these collective results should “reassure physicians regarding the safety of isotretinoin in daily practice.”
“As our time-stratified analysis disclosed that the highest risk of laboratory disturbances occurred 1 to 3 months after drug initiation, we believe that routine laboratory monitoring should be performed in this timeframe, maybe 2 months after commencing treatment,” Emtenani and colleagues concluded.
Perspective
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The goal of laboratory monitoring should be either to guide dosing or to prevent serious adverse effects (eg, pancreatitis). Due to concerns about side effects, patients treated with isotretinoin have historically had monthly laboratory monitoring including lipids, liver function testing and complete blood count. However, this monitoring is not without costs, including financial expense, discomfort from blood draws (particularly relevant given that isotretinoin is often used in adolescence) and the fear of the medication due to the implied risks when patients are told that laboratory monitoring is required.
Fortunately, a growing body of evidence has provided reassurance that laboratory abnormalities are uncommon and rarely of clinical significance, calling into question the value of this frequent monitoring. The study by Emtenani and colleagues evaluating the frequency of abnormalities between those treated with isotretinoin and a matched cohort of individuals treated with oral antibiotics further adds to this literature supporting reduced monitoring. Notably, a recent Delphi consensus study recommended that for young, healthy individuals treated with isotretinoin, monitoring could be limited to checking triglycerides and alanine aminotransferase at baseline and peak dose. The 2024 American Academy of Dermatology Acne Guidelines also state: “For patients undergoing treatment with isotretinoin, we recommend monitoring only [liver function tests] and lipids and not monitoring [complete blood counts].” A recent British Journal of Dermatology Critically Appraised Topic has even called into question whether any laboratory monitoring is required.
However, frequent laboratory monitoring for those treated with isotretinoin remains common, representing a potential evidence-to-practice gap, with some studies estimating cost savings of close to $100 million per year by reducing our use of laboratory monitoring. It is therefore encouraging to see that the work by Emtenani and colleagues further reassurance to those interested in reducing laboratory monitoring for patients treated with isotretinoin for acne.
References:
Affleck A, et al. Br J Dermatol. 2022;doi:10.1111/bjd.21840.
Hansen TJ, et al. J Am Acad Dermatol. 2016;doi:10.1016/j/jaad.2016.03.019.
Reynolds RV, et al. J Am Acad Dermatol. 2024;doi:10.1016/j.jaad.2023.12.017.
Xia E, et al. JAMA Dermatol. 2022;doi:10.1001/jamadermatol.2022.2044.
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