Meta-Analysis of Atopic Dermatitis Drugs Favors Two JAK Inhibitors

Small but statistically significant differences in the safety and efficacy of atopic dermatitis therapies emerged from a systematic review and network meta-analysis of available immunomodulatory options.

Using dupilumab (Dupixent) as the reference standard, the researchers found that the Janus kinase (JAK) inhibitors abrocitinib (Cibinqo) and upadacitinib (Rinvoq) edged out other competitors. Among patients treated for 8 to 16 weeks, abrocitinib 200 mg outperformed the reference on four standard outcome measures, and upadacitinib 30 mg performed better on three of the four metrics, reported Aaron M. Drucker, MD, of the University of Toronto, and colleagues.

None of the other drugs included in the analysis surpassed the results with dupilumab, the researchers noted in the study in JAMA Dermatology.

"With more options available to use for people with severe atopic dermatitis, it's important to understand how these agents compare -- one aspect of which is their relative efficacy," Drucker told MedPage Today in an email.

"Since there are no randomized controlled trials that compare all of the options together, we performed a network meta-analysis of clinical trials to be able to make these comparisons, [and while] it's great that we now have more alternatives ... efficacy is just one parameter to consider when choosing the right medication," he said. "The decision of which medication to choose as a first or subsequent-line agent should be individualized for each person with atopic dermatitis when considering systemic therapy."

The findings came from an updated "living" systematic review and network meta-analysis of immunomodulatory therapies for atopic dermatitis. A prior analysis by the team suggested that dupilumab had efficacy similar to that of higher-dose cyclosporine and was superior to that of methotrexate and azathioprine, but the investigators had insufficient data at that point to draw conclusions about newer biologics and targeted agents.

The update included 60 clinical trials (21 more than the original study) involving 16,579 patients with atopic dermatitis treated for 8 to 16 weeks. Data remained insufficient for a network meta-analysis of pediatric patients or long-term outcomes, the researchers noted.

In addition to dupilumab, abrocitinib, and upadacitinib, the drugs represented in the analysis were baricitinib (Olumiant), tralokinumab (Adtralza), lebrikizumab, ustekinumab (Stelara), nemolizumab, apremilast (Otezla), tezepelumab (Tezspire), fevipiprant, ZPL-3893787, and GBR 830. Some were evaluated at more than one dosage.

The analysis included data for the Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure, Dermatology Life Quality Index, and Peak Pruritus-Numerical Rating Scale. Not all studies included data for all four measures.

With respect to EASI, abrocitinib 200 mg had a mean difference of 2.2 (95% CI 0.2-4.0) and upadacitinib 30 mg had a mean difference of 2.7 (95% CI 0.6-4.7) versus dupilumab, Drucker and co-authors reported.

In contrast, abrocitinib 100 mg had a mean difference of -2.1, baricitinib 4 mg a day a difference of -3.2, baricitinib 2 mg a difference of -5.2, and tralokinumab a difference of -3.5 -- all inferior to dupilumab. Upadacitinib 15 mg had a mean difference of 0.2 versus dupilumab, which was not significant, the researchers said.

A similar pattern was seen with abrocitinib 200 mg and upadacitinib 30 mg for the other three outcomes.

Different drugs and doses carry different risks for adverse events, the investigators noted. For example, abrocitinib 100 mg had a 2.6 times higher risk of serious adverse events compared with dupilumab, which unexpectedly, Drucker said, had a lower risk of serious adverse events compared with placebo.

"Each medication has different safety, cost, and other patient preferences, pros and cons," he said.

Limitations of the analysis, the researchers noted, included differences in clinical trial design and under-representation of certain patient subgroups, so that the findings might not be generalizable. The results were consistent in sensitivity analyses, however, the team added.

Despite the inherent limitations of a network meta-analysis, the findings could still prove useful in clinical settings because of the lack of head-t0-head data, Drucker and co-authors said. "Our finding that abrocitinib, 200 mg daily, and upadacitinib, 30 mg daily, may be associated with slightly better index scores than dupilumab, 600 mg then 300 mg every 2 weeks, is supported by head-to-head trials. Our results may aid shared decision-making between clinicians and patients seeking to understand the relative merits of different treatment options for moderate-to-severe atopic dermatitis."

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