Responsibility lies with derms to promote best practices for isotretinoin

Miami Beach, Fla. - With isotretinoin disappearing from continuous medical education (CME), says an expert, dermatologists must take the initiative in promoting best practices for this indispensable acne drug.

In recent years, says Shannon Humphrey, M.D., “Isotretinoin has been relatively absent from the CME agenda.” Dr. Humphrey, director of CME and clinical instructor, department of dermatology and skin science, University of British Columbia, Vancouver. Because isotretinoin has reached gold-standard status for severe acne - and has gone generic - it’s no longer a priority for drug company funding, she explains.

“It’s important that we keep ourselves abreast of the most recent evidence, as well as best practices in terms of safety and patient outcomes,” says Dr. Humphrey, who spoke at the annual meeting of the American Academy of Dermatology. “As dermatologists, it’s even more important that we stay on the cutting edge of the evidence base behind isotretinoin - so we can model the safest and best practices for our colleagues, and maintain our ability to prescribe it. As we've seen in other countries, the process of accessing this medication has become increasingly legislated and regulated. But there’s really nothing like it in terms of efficacy for acne.”

Far-reaching results

Accordingly, Dr. Humphrey says that isotretinoin’s real-world indications go well beyond its labeled indications (severe, recalcitrant nodular acne). “Patients with scarring, even if their acne is milder, and patients who have psychological distress resulting from any degree of acne may warrant this particularly aggressive treatment.”

In this regard, she notes, “The impact of acne on quality of life and psychosocial functioning does not necessarily correlate with acne severity. Sometimes, patients with milder disease may have the most significant quality-of-life impairment.”

Patients with postinflammatory hyperpigmentation, those who have failed copious conventional treatments, and those with widespread disease unsuited to topical treatment also may warrant isotretinoin, she says.

Standard isotretinoin doses range from 0.5 mg/kg daily to 1 mg/kg daily for up to 20 weeks, for a cumulative dose of 120 mg/kg to 150 mg/kg. Conversely, she says, “Some dermatologists use a long-term low dose; for example, 10 mg three times a week. This practice has not been well studied, and we don’t know clearly the side effect profile if we prescribe this for many years at a time.” But at any dose, she says, “The most significant side effect to remember is teratogenicity. Even a tiny dose can cause retinoid embryopathy.”

Particularly intriguing to Dr. Humphrey are studies of shorter courses that give a lower cumulative dose. In one such study, investigators treated patients with milder acne for an additional four weeks after their acne cleared (using an average cumulative dose of 80.92 mg/kg). Ultimately, patients thusly treated had a two-year relapse rate of 9.35 percent, the same as those who had undergone standard isotretinoin treatment (Borghi A, Mantovani L, Minghetti S, et al. J Eur Acad Dermatol Venereol. 2011;25(9):1094-1098).

Analyzing adverse events

Meanwhile, in the popular media, controversy swirls around isotretinoin’s association with adverse events including depression and suicidal ideation. “However,” Dr. Humphrey says, “the weight of the evidence does not support a causal association.”

Regarding either of these adverse events and isotretinoin, “Most dermatologists and experts agree that there’s been a failure to demonstrate a causal association. But this does not preclude the possibility of an extremely rare, idiosyncratic reaction of depressive symptoms,” she says.

According to a recent population-based study, “Patients with substantial acne - independent from being treated with isotretinoin - actually have a much higher rate of suicidal ideation and social impairment (Halvorsen JA, Stern RS, Dalgard F, et al. J Invest Dermatol. 2011;131(2):363-270).” Specifically, researchers found that 24.1 percent of patients with substantial acne experienced suicidal ideation, versus 18.6 percent of those with moderate acne. “Therefore, these patients at baseline are at much higher risk, which helps to explain some of the patterns that have been reported.”

Regarding inflammatory bowel disease (IBD), Dr. Humphrey says that as in depressive symptoms, “There are so many confounders in both the population and the treatments they’ve had that it's very difficult to produce a clear, final conclusion. But in a recent meta-analysis that pooled data from four large-scale epidemiologic, case-controlled studies, investigators did not find any indication that isotretinoin confers an increased risk of IBD (Etminan M, Bird ST, Delaney JA, et al. JAMA Dermatol. 2013;149(2):216-220). That’s ultimately very reassuring.”

Disclosures: Dr. Humphrey reports no relevant financial interests.