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Pimecrolimus, tacrolimus, and moderate-potency topical corticosteroids (TCS) are the most effective in the treatment of atopic dermatitis (AD), according to a systematic review and meta-analysis.

High-certainty evidence showed that pimecrolimus improved six out of seven patient-important outcomes -- including AD severity, itch, sleep disturbance, eczema-related quality of life, AD flare, any adverse events, and discontinuation of treatment due to adverse events -- while both high- and low-dose tacrolimus improved five of seven, reported Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ontario, and co-authors.

With moderate- to high-certainty evidence, TCS in Groups 4 and 5, indicating moderate potency, improved four and six of these outcomes, respectively, while topical antibiotics were shown to be one of the least effective options, whether used alone or in combination with other treatments, they noted in the .

"With increasing numbers of topical therapy options for patients with AD, achieving optimal AD outcomes requires clarity in the relative merits and potential harms of each treatment approach," Chu's group wrote.

"Previous systematic reviews of topical treatments for AD explored specific subclasses of therapies in isolation, but none have addressed the comparative efficacy and safety among all competing topical treatments," they added. "The abundance of randomized trials but lack of structured and systematically appraised comparative evidence hinders evidence-based decision making by patients, clinicians, and policymakers."

"Considering that AD is the most common chronic inflammatory skin disorder globally, our findings have important and immediate implications for achieving optimal AD outcomes," they concluded.

In randomized trials that assessed AD severity using the SCORAD (SCORing Atopic Dermatitis), high-certainty evidence showed that TCS in Group 1, signifying those with the most potency, was the most effective intervention, with a mean difference from baseline of -17.81 (95% credible interval [CrI] -21.32 to -14.30).

High-dose tacrolimus (mean difference -13.05, 95% CrI -15.15 to -10.95), TCS in Group 2 (mean difference -13.82, 95% CrI -18.74 to -8.89), TCS in Group 3 (mean difference -11.57, 95% CrI -14.80 to -8.37), and TCS in Group 4 (mean difference -12.26, 95% CrI -15.02 to -9.50) demonstrated intermediate superior effectiveness.

There was moderate-certainty evidence that topical antibiotics were not different from control (mean difference -1.48, 95% CrI -6.77 to 3.81).

High-certainty evidence also indicated that high-dose tacrolimus (mean difference -2.27, 95% CrI -2.84 to -1.70) and TCS groups 2, 3, 4, and 5 (mean differences of -3.39 to -2.09) were the most effective treatments for itch, while pimecrolimus appeared to be the most effective treatment for sleep disturbance (mean difference -2.13, 95% CrI -3.15 to -1.01).

High- and moderate-certainty evidence indicated that tacrolimus, pimecrolimus, prescription moisturizers, and TCS in group 5 were the most effective treatments for decreasing flares.

Adverse events were recorded in 130 of the included trials, and high-certainty evidence indicated that TCS in groups 4 and 5 were the best at reducing the number of patients experiencing any adverse events. Moderate-certainty evidence showed that JAK inhibitors, pimecrolimus, and tacrolimus were similar to controls in terms of adverse events.

For this systematic review and meta-analysis, Chu and team searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, WHO's International Clinical Trials Registry Platform, and the Global Resource of EczemA Trials up to Sept. 5, 2022 for randomized trials on AD topical treatments.

They included 219 trials of 68 interventions among 43,123 participants. Of these participants, 11,143 were randomized to control groups and 31,980 to intervention groups. The trials included participants with a median of mean ages of 18.5, and a median 53% were female. The majority of the patients in the trials experienced mild to moderate AD symptoms.

Most of the studies were determined to be at a low risk for bias, with missing outcome data providing the most frequent risk of bias, Chu and team noted. Furthermore, while the included trials spanned over 50 years of data, some smaller studies may have been missed.

Despite these limitations, the findings of this study "illustrate that AD is driven by multiple different inflammatory pathways," similar to other allergic diseases, they wrote, and further research to better help patients choose an AD treatment is needed.

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