Tacrolimus Ointment May Reduce Relapse Risk for Stabilized Atopic Dermatitis

Laurie Barclay, MD

December 01, 2008

December 1, 2008 — Using tacrolimus ointment 3 times weekly was associated with reduced risk for relapse of stabilized atopic dermatitis (AD), according to the results of a 2-phase randomized trial published online November 17 and in the December print issue of Pediatrics.

"Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of [AD] are essential for improving patient quality of life," write Amy S. Paller, MD, from Northwestern University's Feinberg Medical School/Children's Memorial Hospital in Chicago, Illinois, and colleagues from the US Tacrolimus Ointment Study Group. "To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis."

Patients aged 2 to 15 years with moderate to severe AD were randomly assigned to 4 days of twice-daily double-blind treatment with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (phase 1 acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (phase 1 short-term). In phase 2, those patients in whom disease stabilized were again randomly assigned to receive double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week, to clinically normal-appearing skin for up to 40 weeks. Corticosteroid use was not permitted during the trial.

Of 206 patients who were randomized, 152 completed phase 1, and 105 of these patients were randomly assigned to phase 2 (68 received tacrolimus ointment and 37 received vehicle). In phase 1, adverse events were not different between alclometasone and tacrolimus, nor were they different between tacrolimus and vehicle in phase 2. AD signs and symptoms were more improved with alclometasone in the acute period. Thereafter, when all patients applied tacrolimus ointment short term, no differences were observed. Compared with vehicle-treated patients, tacrolimus-treated patients in phase 2 had significantly more disease-free days, significantly longer time to first relapse, and significantly fewer disease relapse days.

"For patients with stabilized moderate to severe [AD], long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle," the study authors write. "Incorporating [topical calcineurin inhibitor]s into a rotational treatment plan that includes topical corticosteroids occurs routinely in clinical practice, and we found that initial treatment with a corticosteroid provides significantly better early relief of the signs and symptoms of AD in pediatric patients with moderate to severe AD than tacrolimus ointment.... Our findings substantiate current clinical practice in the early treatment of AD and provide additional insight into a long-term strategy of disease control for pediatric patients with stabilized moderate to severe AD."

Astellas Pharma US, Inc, supported this study, employs 2 of its authors, and has financial relationships with 4 other authors, 2 of whom also have financial relationships with Novartis Pharmaceuticals Corp.

Pediatrics. 2008;122;e1210–e1218. Article


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