番茄社区

JAK inhibitors increasingly look like the future of therapy for moderate to severe atopic dermatitis (a.k.a. eczema), with another clinical study showing superiority for one such agent over the biologic drug dupilumab (Dupixent).

Upadacitinib (Rinvoq) outperformed the antibody product in achieving 75% reduction in Eczema Area and Severity Index scores (EASI75) in a with moderate to severe atopic dermatitis, reported Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center in Portland, and colleagues .

After 16 weeks on therapy, 71.0% of those assigned to upadacitinib hit the EASI75 mark, compared with 61.1% in the dupilumab group (P=0.006).

"All ranked secondary endpoints also demonstrated the superiority of upadacitinib vs dupilumab," Blauvelt's group added. These included achievement of EASI90 and EASI100, as well as targets for improvement of pruritus.

Adverse events with the JAK inhibitor were common but in line with those seen in numerous previous trials. Upadacitinib is already approved for rheumatoid arthritis and has shown good results in mid- to late-stage studies of psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.

The current study was sponsored by upadacitinib's manufacturer, AbbVie. Patients were mostly in their 30s, with histories of atopic dermatitis going back to childhood. The mean EASI score at enrollment was about 30.

Dupilumab, an interleukin-4/13 inhibitor, is currently the only systemic disease-modifying therapy approved for atopic dermatitis. But, as 番茄社区 noted in a recent look at treatments for the condition, it may take months for the drug to reach peak efficacy. JAK inhibitors -- including baricitinib (Olumiant) and the investigational agent abrocitinib -- have shown faster onset of action in previous trials. The latter, in fact, demonstrated superiority over dupilumab in a trial reported earlier this year. In a bonus for many patients, JAK inhibitors are oral drugs, whereas dupilumab requires injection.

Faster improvement was confirmed in the new upadacitinib trial. Separation was apparent after just 1 week in a line graph showing the proportions of patients in the two treatment groups achieving EASI75 and in mean scores for worst pruritus.

Maximal effects for the JAK inhibitor were achieved at about week 8 for EASI score and by week 5 for worst pruritus. Consistent with dupilumab's slower onset, proportions of patients reaching the EASI 75/90 thresholds were continuing to increase, and mean itch scores were still falling, in the study's final weeks. (That, of course, suggests that the gaps might have disappeared entirely with continued treatment. However, the curve for achievement of EASI100 flattened at less than 10% for dupilumab after 12 weeks, whereas it was still rising at week 16 for upadacitinib, having topped 25%).

Overall, 72% of the upadacitinib group and 63% of those assigned to dupilumab experienced some kind of adverse event. Blauvelt and colleagues had prespecified 16 types as "of special interest." Several of these were more common with upadacitinib than with dupilumab, though all were infrequent:

• Serious infection (seen in 1.1% vs 0.6% of patients)
• Herpes zoster (2.0% vs 0.9%)
• Liver disorder (2.9% vs 1.2%)
• Anemia (2.0% vs 0.3%)
• Neutropenia (1.7% vs 0.6%)
• Creatinine phosphatase elevation (6.6% vs 2.9%)

In addition, treatment-emergent acne was seen in 16% of the upadacitinib group, compared with 2.6% of those on dupilumab. There was one death: a 40-year-old woman in the upadacitinib group suffered pneumonia consequent to flu infection.

Nevertheless, Blauvelt's group was not particularly concerned, asserting that the safety profile was "consistent" with three previous phase III studies and one phase IIb study, "with no new safety risks observed."

Some limitations were noted. Besides the relatively short time frame for the primary and secondary endpoints (an extension study is underway, the group said), the trial design deviated somewhat from ordinary practice in that the drugs were given as monotherapy -- patients who resorted to topical treatment in addition were classed as nonresponders. Also, the trial lacked placebo control.

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