Clinical Question

Is topical tacrolimus (Protopic) safe and effective for the treatment of eczema?

Evidence-Based Answer

For children and adults with moderate to severe eczema, topical tacrolimus is an effective, albeit costly, alternative to topical corticosteroids. Both tacrolimus strengths (0.03% and 0.1%) are superior to low-potency topical corticosteroids, whereas tacrolimus 0.1% has similar effectiveness to moderate- to high-potency topical corticosteroids. A mild, self-limited, local burning sensation is common with use.¹ (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Although topical corticosteroids are the mainstay of treatment for eczema, they can cause skin atrophy on sensitive areas such as the face, eyelids, genitalia, and intertriginous zones. Topical calcineurin inhibitors such as tacrolimus, pimecrolimus (Elidel), and cyclosporine (Sandimmune) are immunosuppressants that do not cause skin atrophy.

The authors of this Cochrane review evaluated 20 randomized controlled trials with 5,885 participants from North America, Europe, Asia, and Africa.¹ The trials compared topical corticosteroids with topical calcineurin inhibitors (primarily tacrolimus) in the treatment of moderate to severe eczema and included adults and children six months or older. Treatment duration ranged from two weeks to one year. Most of the studies were considered high quality with a low risk of bias. Both low- and high-potency tacrolimus (0.03% and 0.1%) were included. Primary outcomes were physician and participant assessments of global improvement (more than 90% subjective improvement being “clear or excellent”) and adverse effects.

The various trial regimens and durations limited the ability of the reviewers to carry out meta-analyses. In studies of children, low-potency tacrolimus (0.03%) was consistently better at achieving physician-assessed improvement than low-potency twice-daily topical corticosteroids. One study reported on the use of once-daily tacrolimus dosing (n = 411; relative risk [RR] = 2.05; 95% confidence interval [CI], 1.36 to 3.08), whereas two studies reported on the use of twice-daily tacrolimus dosing (n = 790; RR = 2.58; 95% CI, 1.96 to 3.38).

In two studies of 1,349 adults, those receiving tacrolimus 0.1% had similar outcomes at three and 12 months to patients receiving mid-potency topical corticosteroids. In one of the studies (n = 972), patients and physicians reported more improvement at six months with tacrolimus 0.1% than did patients and physicians in the topical corticosteroids group (RR = 1.21; 95% CI, 1.13 to 1.29 for patient report; RR = 1.32; 95% CI, 1.17 to 1.49 for physician report). In three studies of 543 patients, tacrolimus 0.1% was better than pimecrolimus 1% in achieving physician-assessed global improvement (RR = 1.80; 95% CI, 1.35 to 2.42). Tacrolimus 0.03% was also somewhat better than pimecrolimus 1% in one study of 139 children (RR = 1.42; 95% CI, 1.02 to 1.98). When comparing the two tacrolimus potencies in six studies of 1,640 patients, the 0.1% potency led to modestly superior physician-assessed improvement scores (RR = 0.82; 95% CI, 0.72 to 0.92).

Regarding tacrolimus use in children, there was no significant difference in the outcome of physician-assessed improvement when patients received once-daily vs. twice-daily dosing, nor between patients treated with high- vs. low-potency strengths.

A local burning sensation was reported by 20% to 60% of participants treated with tacrolimus, but this was generally mild and self-limited. No other adverse effects were more common with tacrolimus.

The U.S. Food and Drug Administration has issued a boxed warning based on animal studies and case reports suggesting a possible association between topical calcineurin inhibitors and lymphoma and skin malignancies.² An excess of malignancies was not observed in the trials reviewed in this Cochrane analysis, although they were not of sufficient size to detect this outcome. Guidelines from the U.S. Food and Drug Administration and the American Academy of Dermatology state that topical calcineurin inhibitors should be second-line therapy for eczema because of their high cost and the potential for minor and more serious adverse effects.^2,3 However, the American Academy of Dermatology guidelines do allow for off-label use of low-dose topical calcineurin inhibitors in children younger than two years.³

The practice recommendations in this activity are available at http://summaries.cochrane.org/CD009864.