OBJECTIVE: In practice, lower dose acitretin therapy (25 mg/d) seems to be better tolerated and associated with fewer abnormalities found after laboratory testing. Here we revisit the original phase 3 trials for acitretin to evaluate the evidence for low-dose therapy producing fewer adverse effects than the 50 mg/d dosage. DESIGN: We retrospectively analyzed pooled data from 2 large pivotal trials, each including a randomized, placebo-controlled, 8-week double-blind phase followed by a 16-week open-label phase. SETTING: Multicenter pivotal trial of subjects in referral centers and private practice. PARTICIPANTS: Subjects with severe psoriasis requiring systemic therapy were recruited according to inclusion/exclusion criteria. INTERVENTION: During the double-blind phase, subjects received placebo or one of several fixed acitretin doses. Dose adjustment was allowed during the open-label phase, during which high-dose treatment was defined as a mean dosage of 50 mg/d and low-dose treatment was defined as a mean dosage of 25 mg/d. MAIN OUTCOME MEASURES: The frequency of anomalies found after laboratory testing and clinical adverse events were the outcomes of interest. RESULTS: Common adverse effects (dry skin, alopecia, rhinitis, etc) were 2 to 3 times more frequent in subjects receiving 50-mg/d acitretin than in those receiving 25 mg/d. Increases in hepatic enzymes and triglycerides in subjects receiving low-dose therapy were minimal compared with levels in those receiving high-dose therapy. CONCLUSIONS: We have shown low-dose therapy (25 mg/d) to be an effective strategy for substantially reducing acitretin-associated adverse effects. Many adverse effects associated with acitretin therapy are dose dependent and can limit the usefulness of this potentially beneficial therapy.
RCT Entities:
OBJECTIVE: In practice, lower dose acitretin therapy (25 mg/d) seems to be better tolerated and associated with fewer abnormalities found after laboratory testing. Here we revisit the original phase 3 trials for acitretin to evaluate the evidence for low-dose therapy producing fewer adverse effects than the 50 mg/d dosage. DESIGN: We retrospectively analyzed pooled data from 2 large pivotal trials, each including a randomized, placebo-controlled, 8-week double-blind phase followed by a 16-week open-label phase. SETTING: Multicenter pivotal trial of subjects in referral centers and private practice. PARTICIPANTS: Subjects with severe psoriasis requiring systemic therapy were recruited according to inclusion/exclusion criteria. INTERVENTION: During the double-blind phase, subjects received placebo or one of several fixed acitretin doses. Dose adjustment was allowed during the open-label phase, during which high-dose treatment was defined as a mean dosage of 50 mg/d and low-dose treatment was defined as a mean dosage of 25 mg/d. MAIN OUTCOME MEASURES: The frequency of anomalies found after laboratory testing and clinical adverse events were the outcomes of interest. RESULTS: Common adverse effects (dry skin, alopecia, rhinitis, etc) were 2 to 3 times more frequent in subjects receiving 50-mg/d acitretin than in those receiving 25 mg/d. Increases in hepatic enzymes and triglycerides in subjects receiving low-dose therapy were minimal compared with levels in those receiving high-dose therapy. CONCLUSIONS: We have shown low-dose therapy (25 mg/d) to be an effective strategy for substantially reducing acitretin-associated adverse effects. Many adverse effects associated with acitretin therapy are dose dependent and can limit the usefulness of this potentially beneficial therapy.