through 48 weeks of follow-up in the JADE EXTEND study, Kristian Reich, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
Dr. Kristian Reich
The head-turning outcomes achieved at the higher studied dose of 200 mg once daily as monotherapy – namely, 87% of patients had an EASI-75 response, defined as at least a 75% reduction from baseline in Eczema Area and Severity Index score, and 62% had an EASI-90 response – herald a new era in the management of atopic dermatitis, predicted Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany).
“I think we will see an evolution in the treatment goals in atopic dermatitis. It’s really good to see nearly 90% of the patients achieved EASI-75 over time. I am completely convinced that if you ultimately want to have a happy patient, you will see treatment goals moving up. We have already seen this in psoriasis. I want to see drugs that give the majority of my patients an EASI-75. And ultimately I want to see EASI-90 for my patients,” he said.
Concurrent with his presentation at the EADV congress, Pfizer announced it has filed for marketing approval of abrocitinib at 100 mg and 200 mg once daily for the treatment of moderate to severe AD. The Food and Drug Administration has granted the application priority review status, with a decision due next April. The company has also filed for marketing approval with the European Medicines Agency.
The JADE EXTEND study is an ongoing extension of the previously reported phase 3, randomized, double-blind, placebo-controlled, 12-week JADE MONO-1 and JADE MONO-2 trials. The two trials included a total of 309 patients on abrocitinib at 200 mg/day and 314 on the selective Janus kinase (JAK) 1 inhibitor at 100 mg/day, 519 of whom subsequently entered the long-term extension study on their same dose. The 70% who required no supplemental topical therapy through 48 weeks were the focus of the analysis presented by Dr. Reich.
The proportion of strong responders increased up until the week 24 or 36 assessments, then remained steady until week 48. For example, the EASI-75 rate in patients on abrocitinib at 200 mg/day rose from 82.5% at week 16, to 86.2% at week 24, 90.1% at week 36, and reached 87.2% at week 48. The EASI-90 rates at the same time points were 56.7%, 64.5%, 65.5%, and 61.6%, respectively. And the EASI-100 rates were 24%, 31.6%, 29.6%, and 24%, respectively.
Not surprisingly, the EASI-75 rates in patients on abrocitinib at 100 mg/day were less robust: 64.4% at week 16, 75.5% at week 24, 74.5% at week 36, and 68% at week 48.
An Investigator’s Global Assessment score of 0 or 1 – that is, clear or almost clear – was achieved at week 16 in 55% of patients on 200 mg/day, 64.5% at week 24, 66% at week 36, and 60.5% at week 48. In patients on the 100-mg dose, the corresponding figures were 36.5%, 46.6%, 53.3%, and 45.2%.
A hallmark of all of the JAK inhibitors under study for AD is what Dr. Reich characterized as “an amazingly fast reduction of itch,” the dominant symptom of the disease. A clinically meaningful reduction of at least 4 points in the Peak Pruritus Numerical Rating Scale – a response of 4 or greater is considered clinically important – from the mean baseline score of 7.1 was present at week 12 in 56.3% of patients on abrocitinib at 200 mg, in 74.3% at week 16, and in 72.5% at week 48. The proportion of patients achieving this endpoint on 100 mg was 41.6% at week 12, 49.4% at week 16, and 52% at week 48.
Serious treatment-emergent adverse events occurred in 6.1% of JADE EXTEND participants on abrocitinib at 100 mg and 12.8% of those on 200 mg. These events included oral herpes and elevated creatine phosphokinase levels. The sole case of pulmonary embolism that occurred during the study was deemed unrelated to treatment.
“What this is telling me here is there are no signals that we haven’t seen earlier with this drug and with other JAK inhibitors before,” the dermatologist observed. “But I want to see more data. I want to see the overall safety, not just for a year, but for 2, 3, 4, and 5 years.”
Asked by an audience member if nonresponsiveness to one JAK inhibitor predicts nonresponse to others, Dr. Reich speculated that it’s likely to be so. He noted that all three of the JAK inhibitors furthest along in the developmental pipeline for atopic dermatitis – abrocitinib, baricitinib, and upadacitinib – are inhibitors of JAK 1, although baricitinib also targets JAK 2.
“I would think that if you really are a nonresponder to any of these that it will be hard to get a good response with the others. We’re not talking about antibodies here, where there may be different epitopes. The affinity is different, and we have seen that if you have no response to a weak TNF [tumor necrosis factor] inhibitor, you can still have a response to a strong TNF inhibitor. I don’t expect the same here,” according to Dr. Reich.
He reported serving as an adviser to and paid clinical research for Pfizer, which sponsored JADE EXTEND, as well as more than two dozen other pharmaceutical companies.