Objective
Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain.

Design
Network meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments.

Data Sources
Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.

Eligibility Criteria for Selected Trials
Included trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory.

Results
We identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6–60 months) topical steroids.

Conclusion
Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema.