Twenty RCTs were included in the review (n=6,288, range 21 to 713). All trials received a Jadad score of at least 3.
Tacrolimus was associated with a significantly better response than control (OR 4.56, 95% CI 2.80 to 7.44; four RCTs), 1% hydrocortisone acetate (OR 3.92, 95% CI 2.96 to 5.20; number of RCTs unclear, results for tests of heterogeneity not reported) and 1% pimecrolimus (OR 1.58, 95% CI 1.18 to 2.12; three RCTs).
Pimecrolimus was associated with a significantly better response than control (OR 3.21, 95% CI 2.48 to 4.14; six RCTs). There was no significant difference in efficacy outcomes with 0.03% compared with 0.1% tacrolimus and with pimecrolimus compared with corticosteroids. Heterogeneity was not significant for any analyses except tacrolimus 0.1% versus 0.03% (I2=56.8) and tacrolimus versus control (I2=57.9)
Quality of life scores were significantly better with 0.1% and 0.03% tacrolimus than with control in children and toddlers in one study (p<0.05). Another study found better quality of life scores with tacrolimus in children, but not toddlers (p<0.05). One study found that 1% pimecrolimus cream had a significantly beneficial effect on the quality of life of parents compared with control.
Adverse events were described as similar with 1% pimecrolimus cream (5% to 86%, 27 withdrawals due to adverse events), tacrolimus ointment (13% to 39%, 11 withdrawals with 0.1% tacrolimus; 15% to 84%, 29 withdrawals with 0.03 tacrolimus) and control (not reported); major adverse events reported were burning and pruritus (text and tables differed).