Low-dose acitretin is associated with fewer adverse events than high-dose acitretin in the treatment of psoriasis.
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.


METHODS
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.


METHODS
Multicenter pivotal trial of subjects in referral centers and private practice.


METHODS
Subjects with severe psoriasis requiring systemic therapy were recruited according to inclusion/exclusion criteria.


METHODS
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.


METHODS
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.
Pearce
Daniel J
DJ
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Klinger
Stephen
S
Ziel
Kristin K
KK
Murad
Emma J
EJ
Rowell
Richard
R
Feldman
Steven R
SR
D017255:Acitretin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012720:Severity of Illness Index
D007641:Keratolytic Agents; D017255:Acitretin