Class Review: Atopic Dermatitis

Despite the FDA’s continued safety review of a newer class of therapeutics, atopic dermatitis remains an active area of interest to researchers, patients, and payers. Atopic dermatitis, or atopic eczema, is a chronic inflammatory skin disorder that can cause intense, persistent itching that can disrupt sleep and daily activities. It occurs in about 7.3% of adults in the United States. Of those affected with the disease, about 40% have moderate or severe symptoms.

Topical treatments are standard of care in dermatitis, but patients who don’t respond to topical therapy need other options.

“We’ve had very few new options available to offer patients. Now we have several new therapies pending approval in the United States that could transform the therapeutic landscape for a topic dermatitis,” Jonathan Silverberg, M.D., Ph.D., associate professor of dermatology at George Washington University School of Medicine and Health Sciences in Washington, D.C., said in an interview.

The only systemic biologic therapy on the market to treat atopic dermatitis is Dupixent (dupilumab), a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13). Developed by Regeneron and Sanofi, Dupixent is approved for three indications: moderate-to-severe atopic dermatitis in people 6 years and older; as an add-on maintenance therapy for moderate-to-severe asthma in people 12 years and older; and as an add-on therapy in adult patients with chronic rhinosinusitis with nasal polyps.

Recently, the Institute for Clinical and Economic Review (ICER) released a final analysis and policy recommendations for atopic dermatitis therapies.

In a 2017 review, ICER found Dupixent to be priced at a cost-effective level. The current analysis shows the current threshold for cost-effectiveness is $29,000 to $39,500 per year, which would require a 6% to 31% discount off the treatment’s current U.S. list price of $41,800.

ICER uses a benchmark it developed, the health-benefit price benchmark (HBPB), a price range suggesting the highest U.S. price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment.

ICER also reviewed several therapies being reviewed by the FDA, including several Janus kinase (JAK) inhibitors. The JAK inhibitors were seen as promising therapies because of their ability to limit the cytokines that trigger inflammation for arthritis, atopic dermatitis, and other conditions.

But in January 2021, a postmarketing cardiovascular safety trial of Pfizer’s Xeljanz (tofacitinib) in patients with rheumatoid arthritis found there was a higher risk of cardiovascular adverse events in patients who received Xeljanz. Xeljanz is currently approved to treat rheumatoid and psoriatic arthritis, as well as ulcerative colitis and juvenile idiopathic arthritis.

Pfizer’s study compared Xeljanz with a TNF inhibitor and included 4,362 patients. The primary analyses included 135 patients with major adverse cardiovascular events (MACE) and 164 subjects with malignancies (excluding non-melanoma skin cancer). The most frequently reported MACE was myocardial infarction, and the most frequently reported malignancy was lung cancer. In those patients with a higher prevalence of known risk factors and malignancy (e.g., older age, smoking), a higher occurrence of events was seen across all treatment groups.

These findings have resulted in regulatory officials looking more closely at safety issues of this and other therapies in the JAK inhibitor class.

“From an efficacy standpoint, the JAK inhibitors look very promising and even appear to be more effective than Dupixent in head-to-head studies and in a meta-analysis, at least for some end points in certain time points,” Silverberg said. “But the FDA has given an indication of clear concerns around safety. We’re waiting to hear back about what the agency will do with respect to their approval in atopic dermatitis.”

One of the JAK inhibitors reviewed by ICER was Eli Lilly’s and Incyte’s Olumiant (baricitinib), which missed its PDUFA action because of the agency’s extended review of safety. At a July 2021 meeting of ICER reviewers, a majority of panelists found that Olumiant, at its current pricing, represents intermediate long-term value with its list price of $29,000 aligning with ICER’s range of $24,400 to $33,300 per year.

ICER reviewers also assessed the JAK inhibitor Rinvoq (upadacitinib) from AbbVie, which they said represents low long-term value for money. With a range of $30,400 to $41,500 per year, Rinvoq would require a 35% to 53% discount off the treatment’s current U.S. list price of $64,300. Although the European Commission in August 2021 approved Rinvoq to treat adults and adolescents with atopic dermatitis, the FDA continues to review the application. In July, AbbVie announced the sNDA for atopic dermatitis would miss its PDUFA date.

The review committee did not vote on long-term value of two other therapies ICER assessed — IL-13 inhibitor Adtralza (tralokinumab) from Leo Pharma and another JAK inhibitor from Pfizer abrocitinib — because these therapies do not yet have a U.S. price.

ICER’s policy recommendations suggest payers establish step therapy with less expensive systemic agents and/or phototherapy to allow patients and clinicians to choose from multiple options rather than require patients to try all options. Clinical experts agreed that it is reasonable to restrict prescriptions for Dupixent, abrocitinib, Olumiant, Adtralza, and Rinvoq to dermatologists or allergy specialists.