Strategies for using topical corticosteroids in children and adults with eczema (Review)

Stephanie Lax, Jane Harvey, Emma Axon, Laura Howells, Matthew Ridd, Stephnie Lawton, Sandra Lawton, Sinead Langan, A Roberts, Amina Ahmed, I Muller, Long Ming, Pavel Chernyshov, Ben Carter, Hywel Williams, Kim S. Thomas, Joanne R. Chalmers

Research output: Contribution to journalArticlepeer-review

Abstract

Background
Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are
uncertainties over their optimal use.

Objectives
To establish the eGectiveness and safety of diGerent ways of using topical corticosteroids for treating eczema.
Search methods
We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT) and five clinical trials
registers. We checked bibliographies from included trials to identify further trials.

Selection criteria
Randomised controlled trials in adults and children with eczema that compared at least two strategies of topical corticosteroid use. We
excluded placebo comparisons, other than for trials that evaluated proactive versus reactive treatment.

Data collection and analysis
We used standard Cochrane methods, with GRADE certainty of evidence for key findings. Primary outcomes were changes in clinicianreported
signs and relevant local adverse events. Secondary outcomes were patient-reported symptoms and relevant systemic adverse
events. For local adverse events, we prioritised abnormal skin thinning as a key area of concern for healthcare professionals and patients.

Main results
We included 104 trials (8443 participants). Most trials were conducted in high-income countries (81/104), most likely in outpatient or other
hospital settings. We judged only one trial to be low risk of bias across all domains. FiJy-five trials had high risk of bias in at least one
domain, mostly due to lack of blinding or missing outcome data.
Stronger-potency versus weaker-potency topical corticosteroids
Sixty-three trials compared different potencies of topical corticosteroids: 12 moderate versus mild, 22 potent versus mild, 25 potent versus
moderate, and 6 very potent versus potent. Trials were usually in children with moderate or severe eczema, where specified, lasting one
to five weeks. The most reported outcome was Investigator Global Assessment (IGA) of clinician-reported signs of eczema.

We pooled four trials that compared moderate- versus mild-potency topical corticosteroids (420 participants). Moderate-potency topical
corticosteroids probably result in more participants achieving treatment success, defined as cleared or marked improvement on IGA (52%
versus 34%;odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41 to 3.04; moderate-certainty evidence). We pooled nine trials that
compared potent versus mild-potency topical corticosteroids (392 participants). Potent topical corticosteroids probably result in a large
increase in number achieving treatment success (70% versus 39%;OR 3.71, 95% CI 2.04 to 6.72; moderate-certainty evidence). We pooled
15 trials that compared potent versus moderate-potency topical corticosteroids (1053 participants). There was insuGicient evidence of a
benefit of potent topical corticosteroids compared to moderate topical corticosteroids (OR 1.33, 95% CI 0.93 to 1.89; moderate-certainty
evidence). We pooled three trials that compared very potent versus potent topical corticosteroids (216 participants). The evidence is
uncertain with a wide confidence interval (OR 0.53, 95% CI 0.13 to 2.09; low-certainty evidence).

Twice daily or more versus once daily application
We pooled 15 of 25 trials inthis comparison (1821 participants, all reported IGA). The trials usually assessed adults and children with
moderate or severe eczema, where specified, using potent topical corticosteroids, lasting two to six weeks.

Applying potent topical corticosteroids only once a day probably does not decrease the number achieving treatment success compared to
twice daily application (OR 0.97, 95% CI 0.68 to 1.38; 15 trials, 1821 participants; moderate-certainty evidence).

Local adverse events
Within the trials that tested 'treating eczema flare-up' strategies, we identified only 26 cases of abnormal skin thinning from 2266
participants (1% across 22 trials). Most cases were from the use of higher-potency topical corticosteroids (16 with very potent, 6 with
potent, 2 with moderate and 2 with mild). We assessed this evidence as low certainty, except for very potent versus potent topical
corticosteroids, which was very low-certainty evidence.

Longer versus shorter-term duration of application for induction of remission
No trials were identified.

Twice weekly application (weekend, or ‘proactive therapy') to prevent relapse (flare-ups) versus no topical corticosteroids/reactive
application

Nine trials assessed this comparison, generally lasting 16 to 20 weeks. We pooled seven trials that compared weekend (proactive) topical
corticosteroids therapy versus no topical corticosteroids (1179 participants, children and adults with a range of eczema severities, though
mainly moderate or severe).

Weekend (proactive) therapy probably results in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio (RR) 0.43, 95% CI
0.32 to 0.57; 7 trials, 1149 participants; moderate-certainty evidence).

Local adverse events
We did not identify any cases of abnormal skin thinning in seven trials that assessed skin thinning (1050 participants) at the end of
treatment. We assessed this evidence as low certainty.

Other comparisons
Other comparisons included newer versus older preparations of topical corticosteroids (15 trials), cream versus ointment (7 trials), topical
corticosteroids with wet wrap versus no wet wrap (6 trials), number of days per week applied (4 trials), different concentrations of the same topical corticosteroids (2 trials), time of day applied (2 trials), topical corticosteroids alternating with topical calcineurin inhibitors versus
topical corticosteroids alone (1 trial), application to wet versus dry skin (1 trial) and application before versus aJer emollient (1 trial). No
trials compared branded versus generic topical corticosteroids and time between application of emollient and topical corticosteroids.

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