from baseline (0.09 and 0.34) peaking at week 2 (0.38 and 0.41, respectively, where 1=mild), returning to below, or similar to baseline levels by week 12. Again, mean scores were low (where 1=mild) over the course of the studies. Hyperpigmentation (N=145, 18.6%) was more commonly reported than hypopigmentation (N=26, 3.4%) at baseline. There were no increases in severity (mean scores) with treatment.
DISCUSSION
Topical retinoids provide the mainstay of acne treatment. While they have been shown to be very effective either as monotherapy or in combination, they are capable of producing cutaneous irritancy during the first few weeks of application. These side effects vary in severity and duration, appear to be compound and vehicle dependent, and can both limit treatment and reduce patient adherence. Studies suggest tazarotene 0.1% (gel, foam, or cream) may be the most effective retinoid, but its potential for cutaneous irritation is also the greatest. While tazarotene 0.1% foam may overcome some of the aesthetic disadvantages of gels and creams (they have been reported to leave a greasy, sticky residue and can be difficult to apply evenly16), no data are available on patient preferences and clinical benefits17 are similar to those reported in other randomized, double-blind studies of tazarotene 0.1% cream2 and gel.18 Treatment-emergent AEs such as application site irritation (18% and 11%, study 1 and 2 respectively), dryness (6% and 8%), and erythema (9% and 4%) were still common, especially over the first four weeks treatment.
The rationale behind the novel formulation of tazarotene 0.045% lotion was to develop a topical treatment for moderate or severe acne; providing optimal efficacy and minimizing the tazarotene irritant effects in a light and aesthetically pleasing lotion formulation, where lotion is the preferred formulation for facial application. The formulation process utilized new polymeric emulsion technology to ensure uniform distribution of tazarotene and moisturizing ingredients onto the skin surface and efficient delivery into the epidermal layers. A comparative study of tazarotene 0.045% lotion and tazarotene 0.1% cream in moderate- to-severe acne reported numerically greater efficacy with tazarotene 0.045% lotion at 12 weeks despite half the concentration of tazarotene and fewer treatment-related AEs.15
Following the promising phase 2 results, we further investigated the safety and efficacy of tazarotene 0.045% lotion, reporting on two phase 3 clinical studies in moderate-to-severe acne in subjects 9 years and older. Treatment success was achieved in close to 30% of subjects by week 12; with significant reductions in both inflammatory and comedonal lesions, compared with vehicle (P<0.001). Tazarotene 0.045% lotion was also well-tolerated. Most common treatment-related AEs were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Application site reactions were less common than those reported previously with tazarotene 0.1% gel, cream or foam and may be as a result of formulation benefits as well as the lower concentration of tazarotene. Overall cutaneous tolerability and safety scores were also low. There were slight transient increases peaking at week 2 with scores returning to below or similar to baseline levels by week 12.
The rationale behind the novel formulation of tazarotene 0.045% lotion was to develop a topical treatment for moderate or severe acne; providing optimal efficacy and minimizing the tazarotene irritant effects in a light and aesthetically pleasing lotion formulation, where lotion is the preferred formulation for facial application. The formulation process utilized new polymeric emulsion technology to ensure uniform distribution of tazarotene and moisturizing ingredients onto the skin surface and efficient delivery into the epidermal layers. A comparative study of tazarotene 0.045% lotion and tazarotene 0.1% cream in moderate- to-severe acne reported numerically greater efficacy with tazarotene 0.045% lotion at 12 weeks despite half the concentration of tazarotene and fewer treatment-related AEs.15
Following the promising phase 2 results, we further investigated the safety and efficacy of tazarotene 0.045% lotion, reporting on two phase 3 clinical studies in moderate-to-severe acne in subjects 9 years and older. Treatment success was achieved in close to 30% of subjects by week 12; with significant reductions in both inflammatory and comedonal lesions, compared with vehicle (P<0.001). Tazarotene 0.045% lotion was also well-tolerated. Most common treatment-related AEs were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Application site reactions were less common than those reported previously with tazarotene 0.1% gel, cream or foam and may be as a result of formulation benefits as well as the lower concentration of tazarotene. Overall cutaneous tolerability and safety scores were also low. There were slight transient increases peaking at week 2 with scores returning to below or similar to baseline levels by week 12.
CONCLUSIONS
Tazarotene 0.045% lotion utilizes new polymeric emulsion
technology with moisturizing excipients to provide a topical
treatment for moderate-to-severe acne that is effective and
well-tolerated. With half the concentration of other marketed
formulation (gel, foam, or cream) it appears to be at least as effective
and demonstrates a better safety and tolerability profile.
DISCLOSURES
Drs Tanghetti, Werschler, and Lain are investigators and/or advisors
to Ortho Dermatologics. Drs Guenin and Pillai and Ms
Martin are employees of Bausch Health.
ACKNOWLEDGMENTS
We thank Brian Bulley, MSc (Konic Limited, UK) for assistance
with the preparation of the manuscript. Valeant Pharmaceuticals,
funded Konic’s activities pertaining to this manuscript.
REFERENCES
1. Leyden JJ, Shalita A, Thiboutot D, et al. Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment. Clin Ther. 2005;27(2):216-224.
2. Shalita AR, Berson DS, Thiboutot DM, et al. Effects of tazarotene 0.1 % cream in the treatment of facial acne vulgaris: pooled results from two multicenter, double-blind, randomized, vehicle-controlled, parallel-group trials. Clin Ther. 2004;26(11):1865-1873.
3. Leyden J, Thiboutot DM, Shalita AR, et al. Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, doubleblind, randomized, parallel-group study. Arch Dermatol. 2006;142(5):605-612
4. Draelos ZD, Tanghetti EA. Optimizing the use of tazarotene for the treatment of facial acne vulgaris through combination therapy. Cutis. 2002;69(2 Suppl):20-29.
5. Tanghetti E, Abramovits W, Solomon B, et al. Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial. J Drugs Dermatol. 2006;5(3):256-261
6. Leyden JJ, Tanghetti EA, Miller B, et al. Once-daily tazarotene 0.1 % gel versus once-daily tretinoin 0.1 % microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial. Cutis. 2002;69(2 Suppl):12-19.
7. Webster GF, Guenther L, Poulin YP, et al. A multicenter, doubleblind, randomized comparison study of the efficacy and tolerability of oncedaily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis. 2002;69(2 Suppl):4-11.
8. Webster GF, Berson D, Stein LF, et al. Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis. 2001;67(6 Suppl):4-9.
9. Leyden J, Lowe N, Kakita L, et al. Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial. Cutis. 2001;67(6 Suppl):10-16.
10. Shalita A, Miller B, Menter A, et al. Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. J Drugs Dermatol. 2005;4(2):153-158.
11. Tanghetti E, Dhawan S, Green L, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treat-
2. Shalita AR, Berson DS, Thiboutot DM, et al. Effects of tazarotene 0.1 % cream in the treatment of facial acne vulgaris: pooled results from two multicenter, double-blind, randomized, vehicle-controlled, parallel-group trials. Clin Ther. 2004;26(11):1865-1873.
3. Leyden J, Thiboutot DM, Shalita AR, et al. Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, doubleblind, randomized, parallel-group study. Arch Dermatol. 2006;142(5):605-612
4. Draelos ZD, Tanghetti EA. Optimizing the use of tazarotene for the treatment of facial acne vulgaris through combination therapy. Cutis. 2002;69(2 Suppl):20-29.
5. Tanghetti E, Abramovits W, Solomon B, et al. Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial. J Drugs Dermatol. 2006;5(3):256-261
6. Leyden JJ, Tanghetti EA, Miller B, et al. Once-daily tazarotene 0.1 % gel versus once-daily tretinoin 0.1 % microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial. Cutis. 2002;69(2 Suppl):12-19.
7. Webster GF, Guenther L, Poulin YP, et al. A multicenter, doubleblind, randomized comparison study of the efficacy and tolerability of oncedaily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis. 2002;69(2 Suppl):4-11.
8. Webster GF, Berson D, Stein LF, et al. Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis. 2001;67(6 Suppl):4-9.
9. Leyden J, Lowe N, Kakita L, et al. Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial. Cutis. 2001;67(6 Suppl):10-16.
10. Shalita A, Miller B, Menter A, et al. Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. J Drugs Dermatol. 2005;4(2):153-158.
11. Tanghetti E, Dhawan S, Green L, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treat-
