Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis

March 2020 | Volume 19 | Issue 3 | Original Article | 272 | Copyright © March 2020


Published online March 1, 2020

Emil A. Tanghetti , William Philip Werschler , Edward Lain , Eric Guenin , Susan Harris , Anya Loncaric , Radhakrishnan Pillai

aCenter for Dermatology and Laser Surgery, Sacramento, CA bUniversity of Washington, School of Medicine, Seattle, WA cAustin Institute for Clinical Research, Austin, TX dOrtho Dermatologics, Bridgewater, NJ eBausch Health US, LLC, Petaluma, CA





Statistical analyses were conducted using SAS® software, version 9.3 or later. AEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology for the safety population.

RESULTS

Patient Disposition and Demographics
In this pooled analysis, a total of 1614 patients were randomized to tazarotene 0.045% lotion (n=799) or tazarotene lotion vehicle (n=815; Figure 1). Of these, 692 (86.6%) and 722 (88.6%) completed the study, respectively. The most common reasons for study discontinuation were lost to follow up (45, 5.6%) and patient request (34, 4.3%) in the tazarotene 0.045% lotion arm, and lost to follow up (56, 6.9%) and patient request (23, 2.8%) in the vehicle arm. AEs led to study discontinuation in 19 (2.4%) and 4 (0.5%) of patients in the tazarotene and vehicle arms, respectively. The safety population consisted of 1570 patients (tazarotene n=779; vehicle n=791), with 44 patients not included due to lack of any post-baseline safety evaluation.

Patient demographics and disease characteristics at baseline are shown in Table 1 and baseline QoL scores in Table 2. Characteristics were well matched between the two arms. The mean age overall was 20.5 years (standard deviation [SD] 6.9) and the majority of patients (65.9%) were female. All patients had moderate (EGSS 3) or severe (EGSS 4) disease, the latter comprising 9.1% and 9.1% of the tazarotene and vehicle arms, respectively.

Efficacy Evaluations
Significantly more patients in the tazarotene 0.045% arm than in the vehicle arm achieved the co-primary endpoint of treatment success, defined as achieving at least a 2-grade improvement in EGSS with a final score of clear or almost clear (30.4% vs 17.9%, P<0.001; Figure 2).

Tazarotene 0.045% lotion was associated with significant reductions in inflammatory lesion counts (Figure 3) as well as noninflammatory lesion counts (Figure 4) compared with vehicle. Mean inflammatory lesion counts were reduced 57.9% and 47.8% in the tazarotene and vehicle arms, respectively (P<0.001) at week 12; significant differences between tazarotene and vehicle were observed by week 8 (Figure 3). Significant reductions in noninflammatory lesion counts were observed as early as week 4 (32.6% vs 24.2%; P<0.001) and were further reduced at week 8 (46.6% vs 33.6%; P<0.001) and week 12 (56.0% vs 42.0%; P<0.001; Figure 4).

Improvements in Acne-Specific QoL scores at week 12 were numerically greater for the tazarotene 0.045% cohort versus vehicle in all 4 domains (self-perception: 7.5 vs 6.7; role emotional: 6.0 vs 5.5; role-social: 4.7 vs 4.1; acne symptoms: 6.4 vs 5.3; Table 2).

Safety Evaluations
Safety results for the pooled studies have been reported.22 Treatment-emergent AEs (TEAEs) were reported by 209 patients