ICER Review of AD Therapies Narrowly Supports JAK Inhibitors, Depending on Safety

Using findings in an earlier report from the Institute for Clinical and Economic Review (ICER), the New England Comparative Effectiveness Public Advisory Council (CEPAC) narrowly voted that 3 Janus kinase (JAK) inhibitors for atopic dermatitis (AD) provide a net health benefit.

Recently, the FDA delayed decisions on baricitinib, ruxolitinib cream, and abrocitinib for AD. In April, the FDA also issued a complete response letter for the biologic tralokinumab.

The New England CEPAC voted 11-2 on tralokinumab, 9-4 on upadicitinib, 8-6 on abrocitinib, and 7-6 on baricitinib that the evidence was adequate to demonstrate the therapies when added to usual care provided a net health benefit in adults with moderate to severe AD. For adolescents with mild to moderate AD, CEPAC voted 12-1 that the evidence was adequate to demonstrate ruxolitinib cream provided a net health benefit compared with topical emollients alone.

In the report, ICER noted that quantitative indirect comparisons and head-to-head comparisons have shown that higher doses of upadacitinib and abrocitinib are possibly more effective than dupilumab, while baricitinib and tralokinumab are likely less effective than dupilumab.

“For many people, atopic dermatitis is a relatively mild condition, but atopic dermatitis can be a severe, chronic disease with significant effects on quality of life,” David Rind, MD, ICER’s chief medical officer, said in a statement. “Dupilumab was a major advance, but it does not work for all patients, and new therapies are needed.”

When reviewing the therapies, they weighed other potential benefits, disadvantages, and contextual considerations, such as the need for treatments, the lifetime impact, the ability of patients to achieve major life goals, and caregivers’ own quality of life. Rind nodded to the safety concerns with JAK inhibitors, which have led to the FDA delaying decisions, but added that if they are safe, many patients will benefit from them joining the treatment landscape.

“A big issue with the Janus kinase inhibitors, including some which are on the market now for other diseases, is that they all have black box warnings,” David Pariser, MD, senior physician at Pariser Dermatology Specialists and professor at Eastern Virginia Medical School Department of Dermatology, explained in an interview with The American Journal of Managed Care® in 2020. “And they all will have safety issues….So, it will be a safety versus efficacy trade off, an oral drug versus checkable drug trade off.”

In addition, dupilumab now has long-term data showing the safety and efficacy of the treatment, which has alleviated ICER’s original concerns when it reviewed the therapy in 2017.

Another concern with new therapies is the high price tag. Rind noted that there was discussion during the public meeting that new therapies should improve the health of patients without aggravating health inequities.

“Clinical experts and patients highlighted that the high cost of new therapies might worsen disparities in accessing care,” he said.

ICER compared the cost and effectiveness of the therapies using estimated net prices for baricitinib, upadacitinib, and dupilumab, which are currently marketed; the average of the net prices of baricitinib and upadacitinib for abrocitinib; and dupilumab’s net price as a placeholder for tralokinumab. The estimated Health Benefit Price Benchmarks range for each intervention is:

• Abrocitinib: $30,600 to $41,800
• Baricitinib: $24,400 to $29,000
• Tralokinumab: $25,700 to $35,000
• Upadacitinib: $30,400 to $41,500
• Dupilumab: $29,000 to $39,500

ICER also provided policy recommendations based on the discussion with CEPAC. One of the recommendations was that payers make available at least 1 biologic (dupilumab/tralokinumab) and 1 oral JAK inhibitor if multiple agents are approved.

“Clinician experts emphasized that the heterogeneity of atopic dermatitis and the challenges in defining and measuring disease severity support the need for having access to a range of different therapies,” according to the report.

Additionally, when payers do establish step therapy, patients and clinicians should be able to choose from multiple options instead of requiring patients try all options. Step therapy should only be implemented if it provides adequate flexibility for patients of different needs and if implementation is transparent and efficient.

“While it is possible to tailor step therapy in a clinically responsible fashion, it is often administered with documentation burdens and inadequate procedures for exceptions that make step therapy a source of great frustration and the cause of poor outcomes for some patients due to the discontinuation of medicine/missed doses,” according to the report. “A particular area of concern raised by patients involved requirements to re-step through previously failed therapies when insurance changed.”