Phase 4 study reaffirms safety of low-dose acitretin

September 1, 2006

Results of a phase 4, open-label, multicenter study indicate that low-dose acitretin (Soriatane, Connetics) in moderate to severe psoriasis patients provides efficacy as monotherapy by 24 weeks, but requires patience, said Gerald G. Krueger, M.D., at the American Academy of Dermatology's Academy '06.

Results of a phase 4, open-label, multicenter study indicate that low-dose acitretin (Soriatane, Connetics) in moderate to severe psoriasis patients provides efficacy as monotherapy by 24 weeks, but requires patience, said Gerald G. Krueger, M.D., at the American Academy of Dermatology's Academy '06.

Dr. Krueger, professor of dermatology, University of Utah, Salt Lake City, reported the results for the trial that enrolled 136 patients who were randomized to receive acitretin 25 mg once daily for 24 weeks or acitretin 25 mg once daily for 12 weeks followed by acitretin 10 mg once daily for 12 weeks.

Follow-up visits were scheduled at weeks two, four, eight, 12, 20 and 24. Dosage reduction for safety reasons was allowed at any time during the study, and dosage increases up to 35 mg per day were allowed as needed for optimizing efficacy beginning at week 12 in both groups.

At week 24, a PASI 75 response (75 percent reduction from baseline PASI score) was achieved in 31 percent of patients assigned to be maintained at the 25 mg dose and in 14 percent of the patients in the dose reduction group. Results of the investigator-rated Overall Lesional Assessment (OLA) showed 12 percent of subjects in both groups had none to minimal psoriasis at week 12; at week 24, the responder rate increased to 38 percent of patients in the acitretin 25 mg group but only to 14 percent among patients assigned to undergo dosage reduction. These results were relatively consistent with the Subject's Global Assessment. An analysis of response by body weight revealed the best efficacy was achieved among patients who weighed the least.

"Acitretin is the only oral retinoid approved for initial and maintenance therapy of severe psoriasis, and current labeling recommends initiating treatment at 25 to 50 mg daily. Although there have been some reports indicating the 25 mg dose is quite effective in providing dramatic responses, the outcomes in this open study investigating low-dose treatment are less favorable," Dr. Krueger says.

"Nevertheless, this study reaffirms the safety of low-dose acitretin and reinforces consideration of its use in conjunction with phototherapy or a systemic agent for a substantially augmented treatment response without an anticipated increase in side effects."

STUDY DETAILS

The phase 4 study was undertaken at the urging of members of the medical advisory board for Connetics who were skeptical about the available positive data on response rates using low-dose acitretin as stand-alone therapy. The 136 patients enrolled had a mean body surface area (BSA) of psoriasis involvement of about 20 percent at baseline (range, 10 to 75) and a mean PASI score of about 14 (range, 3 to 48). About two-thirds of the patients were judged to have moderate disease in the investigator-rated OLA, and the rest were severe (about one-third) or very severe (about 5 percent).

During the first 12 weeks of treatment, there was no need for dosage adjustment because of safety issues, and the mean daily dose of acitretin in both groups was 25 mg. Despite the reduction in dose per protocol to 10 mg, the mean daily dose of acitretin in that group was nearly identical during the second 12 weeks of the study compared with the stable-dose group, 26 mg versus 29 mg, respectively.

"During the second 12-week period, subjects who went to the lower-dose arm were permitted to go back to a higher dose if their disease worsened and the investigator and the patient were in agreement that a higher dose was warranted. At our center, patients who were switched to the lower dose at week 12 often needed extra visits to re-evaluate dosing for better disease control," Dr. Krueger explains.

"Nevertheless, if a patient is given acitretin as monotherapy and achieves sufficient improvement using the 25 mg dose, the results of this study support consideration of reducing the dose, recognizing that close follow-up may be needed to monitor disease status," he adds.