Data from two phase 3, multicenter, randomized, double-blind studies (Study 1 [NCT02462070]; Study 2 [NCT02462122]) of HP/TAZ fixed combination lotion in patients with moderateto- severe psoriasis were pooled for this post hoc analysis.10,11 The methodology for the 2 individual studies has been previously published10,11 and is described briefly here. Participants were randomized (2:1) to receive HP/TAZ lotion or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up. Participants were instructed to apply a thin layer of HP/TAZ or vehicle lotion over the affected areas as designated by the investigator; the maximum allowable weekly usage was 50 gm. CeraVe® hydrating cleanser and CeraVe® moisturizing lotion (L’Oreal, NY) were provided as needed for optimal moisturization/ cleaning of the skin.
All participants were required to be ≥18 years of age and have a clinical diagnosis of psoriasis, an Investigator’s Global Assessment (IGA) score of 3 or 4 (5-point scale; 0=clear and 4=severe), and affected Body Surface Area (BSA) of 3% to 12%; face, scalp, palms, soles, axillae, and intertriginous areas were excluded from these calculations. For all participants, the target lesion must have covered an area between 16-100 cm2 in size and could not be located on any area covering bony prominences (eg, knees). In addition, the lesion must be associated with a score of ≥3 for at least 2 of 3 signs of psoriasis (erythema, plaque elevation, and scaling [5 point scale; 0=clear and 4=severe]), a score sum of at least 8, and could not have had a score of 0 or 1 for any one of the signs.
Written informed consent was required from participants prior to the conduct of any study-related procedures. The protocol was approved by institutional review boards (IRBs) or ethics committees at all investigational sites. Studies were conducted in accordance with the protocol, the ethical principles of Good Clinical Practice (GCP), International Council for Harmonisation (ICH), and the Declaration of Helsinki.
Post Hoc Analyses
Post hoc analyses were conducted using data from the subset of patients from the pooled overall intent-to-treat population (ITT) whose target lesion was on the lower extremities (leg). Treatment success at the leg target lesion, was defined as a ≥2-grade improvement from baseline and was evaluated for each individual sign of psoriasis (erythema, plaque elevation, and scaling). Overall treatment success, which considered all treatment areas in addition to the target lesion was defined as a ≥2-grade improvement from baseline in IGA score and a score of ‘clear’ or ‘almost clear’ [0 or 1]. Reductions from baseline in overall mean BSA and the IGAxBSA composite tool were also evaluated. Change from baseline in IGAxBSA was calculated by multiplying the IGA score by the total BSA. Reductions from baseline of ≥50% and ≥75% in IGAxBSA score (IGAxBSA-50 and IGAxBSA-75) were also tabulated. The IGA, BSA, and IGAxBSA composite assessments did not include areas of the face, scalp, palms, soles, axillae, and other intertriginous areas; palms and soles with psoriasis could be treated with the study drug but were not included in these assessments.
Efficacy analyses were conducted in the ITT analysis population, defined as participants who were randomized, received study drug, and presented with a target lesion on the leg. Safety parameters were assessed using the safety population, defined as participants from the ITT analysis population who had postbaseline safety data. Treatment success data (signs of psoriasis and overall) were analyzed by using Cochran-Mantel-Haenszel (CMH) tests stratified by analysis center with all values adjusted for multiple imputations. Markov chain Monte Carlo (MCMC) multiple imputation was used to impute missing values. Affected BSA was evaluated using an analysis of covariance with factors of treatment and study center and baseline affected BSA as a covariate; there was no imputation of missing data. Mean change in IGAxBSA composite tool was examined using a Wilcoxon Rank Sum Test with last observation carried forward (LOCF) used to impute missing IGA and BSA data through week 8 prior to analysis. IGAxBSA-50 and -75 parameters were assessed using CMH test with LOCF used to impute missing values through week 8. Safety was evaluated via assessment of AEs through week 8. All treatment areas were examined at each visit for the presence or absence of skin atrophy, striae, telangiectasia, and folliculitis, AEs known to be related to HP/TAZ.
A total of 418 participants were randomized to once-daily HP/ TAZ or vehicle lotion (Study 1, n=203 [HP/TAZ, n=135; vehicle, n=68]; Study 2, n=215 [HP/TAZ, n=141; vehicle, n=74]) (Figure 1). A total of 219 participants (52.4%) were identified as having a leg target lesion and were included in the analysis. Of those, 148 participants received once-daily HP/TAZ lotion and 71 received vehicle. A total of 82.4% of participants completed HP/TAZ treatment compared with 78.9% that completed vehicle treatment. Demographics and baseline characteristics were generally