Another vehicle-controlled study of 1% pimecrolimus in atopic dermatitis: how does it help clinicians and patients, and is it ethically sound?

Abstract

Question: What is the efficacy and safety of 1% pimecrolimus cream compared with vehicle in children with atopic dermatitis (AD)? Design: A combined analysis of 2 identical randomized controlled clinical trials (N=403). Setting: Children attending specialist dermatology units in the United States. Study Participants: Children and adolescents aged 1 to 17 years with AD as defined by the United Kingdom Working Party’s refinement of Hanifin and Rajka’s diagnostic criteria. Those entered into the study had to have at least 5% body surface area involvement and investigators’ global assessment (IGA) baseline score of 2 to 3 (mild to moderate AD) and no treatment except emollients in the 7 days prior to randomization. Children who had received systemic therapy within 1 month prior to the study were excluded. Intervention: Application of 1% pimecrolimus cream twice daily for 6 weeks vs vehicle only. Participants were randomized in a ratio of 2:1 in favor of 1% pimecrolimus cream. Outcome Measures: The primary outcome measure was the proportion of children who, in the view of the investigator, had achieved a category of 0 or 1 on the IGA scale. The IGA scale was based on descriptions of AD signs to define 6 categories from 0 to 5 representing clear, almost clear, mild disease, moderate disease, severe disease, and very severe disease, respectively. Secondary outcome measures included EASI (a composite scale of the 4 signs of erythema, papulation/induration, excoriation, and lichenification combined with extent), patient/caregiver-rated severity of pruritus on a 4-point scale, and patient/caregiverrated overall disease control on a 4-point scale. Safety assessments includedstandardmonitoringof adverseevents, as well as hematologic and biochemistry assessments and urinalysis. Outcomes were measured on days 8, 15, 22, 29, and 43 (end of treatment period). Results: At the end of 6 weeks, 35% of participants in the pimecrolimus group (93/267) attained an IGA of 0 or 1 (clear or almost clear) compared with 18% in the vehicleonly group (25/136) based on an intention-to-treat analysis (P .05). The number needed to treat with pimecrolimus to achieve 1 additional success compared with vehicle was 6. Secondary outcomes showed similar magnitudes of improvement in the pimecrolimus group, and improvements were noted as early as day 8. Adverse events were similar in both groups. In particular, application site burning was noted in 10.4% and 12.5% of pimecrolimus and vehicle groups, respectively. Authors’ Conclusion: Application of 1% pimecrolimus cream appears to be a safe and effective alternative to currently used therapies in AD. Four of the authors were employees of Novartis Pharmaceuticals, which manufactures pimecrolimus, and the remaining 4 had declared conflicts of interest relating to various associations with Novartis Pharmaceuticals.