Clinical Review

Novel Psoriasis Therapies and Patient Outcomes, Part 1: Topical Medications

Cutis. 2015 March;95(3):164-168, 170

References

1. Mason A, Mason J, Cork M, et al. Topical treatments for chronic plaque psoriasis: an abridged Cochrane systematic review. J Am Acad Dermatol. 2013;69:799-807.

2. Nazarian R, Weinberg JM. AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. Curr Opin Investig Drugs. 2009;10:1236-1242.

3. Moustafa F, Feldman SR. A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology. Dermatol Online J. 2014;20:22608.

4. Halpert G, Sredni B. The effect of the novel tellurium compound AS101 on autoimmune diseases. Autoimmun Rev. 2014;13:1230-1235.

5. Ports WC, Khan S, Lan S, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169:137-145.

6. Yosipovitch G, Roblin D, Traversa S, et al. A novel topical targeted anti-pruritic treatment in phase 2b development for chronic pruritus. Paper presented at: 72nd Annual Meeting of the American Academy of Dermatology; March 21-25, 2014; Denver, CO.

7. Kang S, Yi S, Griffiths CE, et al. Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions. Br J Dermatol. 1998;138:77-83.

8. Kristl J, Slanc P, Krasna M, et al. Calcipotriol affects keratinocyte proliferation by decreasing expression of early growth response-1 and polo-like kinase-2. Pharm Res. 2008;25:521-529.

9. Tiberio R, Bozzo C, Pertusi G, et al. Calcipotriol induces apoptosis in psoriatic keratinocytes. Clin Exp Dermatol. 2009;34:e972-e974.

10. Luger T, Seite S, Humbert P, et al. Recommendations for adjunctive basic skin care in patients with psoriasis. Eur J Dermatol. 2014;24:194-200.

11. Dermipsor reports good results in DPS-101 Phase IIb study for plaque psoriasis [press release]. Evaluate Web site. http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=250042. Published October 15, 2007. Accessed February 13, 2015.

12. Rivera AM, Hsu S. Topical halobetasol propionate in the treatment of plaque psoriasis: a review. Am J Clin Dermatol. 2005;6:311-316.

13. Punwani N, Scherle P, Flores R, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012;67:658-664.

14. Efficacy and safety of calcipotriol plus hydrocortisone ointment compared with tacalcitol ointment in patients with psoriasis on the face and skin folds (NCT00640822). https://clinicaltrials.gov/ct2/show/results/NCT00640822?term=NCT00640822&rank=1. Updated October 21, 2013. Accessed May 30, 2014.

15. Product candidates: targeting p-STAT3 for improved psoriasis treatment. Moleculin Web site. http://moleculin.com/product-candidates/mol4239. Accessed February 13, 2015.

16. Chowdhari S, Saini N. hsa-miR-4516 mediated downregulation of STAT3/CDK6/UBE2N plays a role in PUVA induced apoptosis in keratinocytes. J Cell Physiol. 2014;229:1630-1638.

17. Paired psoriasis lesion, comparative, study to evaluate MOL4239 in psoriasis (NCT01826201). https://clinicaltrials.gov/ct2/show/results/NCT01826201?term=NCT01826201&rank=1&sect=X01256#all. Updated December 22, 2014. Accessed February 25, 2015.

18. Clinical development pipeline. Moleculin Web site. http://moleculin.com/clinical-trials/psoriasis-trials. Accessed February 13, 2015.

19. de la Brassinne M, Nikkels A. Psoriasis: state of the art 2013. Acta Clin Belg. 2013;68:433-441.

20. Ross MI. Intralesional therapy with PV-10 (Rose Bengal) for in-transit melanoma. J Surg Oncol. 2014;109:314-319.

21. Bissonnette R, Bolduc C, Maari C, et al. Efficacy and safety of topical WBI-1001 in patients with mild to moderate psoriasis: results from a randomized, double-blind placebo-controlled, phase II trial. J Eur Acad Dermatol Venereol. 2012;26:1516-1521.

AS101 (Integrin Inhibitor)

AS101 (BioMAS Ltd), or ammonium trichloro (dioxoethylene-o,o') tellurate, acts as stimulator of regulatory T cells and a redox modulator inhibiting the leukocyte integrins α₄β₁ and α₄β₇ that enable CD4⁺ T-cell and macrophage extravasation; it also limits expression of the inflammatory cytokines IL-6 and IL-17.⁴ A randomized, placebo-controlled, double-blind, phase 2 study evaluating the efficacy of AS101 cream 4% twice daily for 12 weeks was withdrawn prior to enrollment (NCT00788424).

Tofacitinib (Janus Kinase 1 and 3 Inhibitor)

Tofacitinib (formerly known as CP-690,550)(Pfizer Inc) is a selective Janus kinase (Jak) 1 and Jak3 inhibitor that limits expression of cytokines that promote inflammation (eg, IFN-γ) and inhibits helper T cells (T_H17) by downregulating expression of the IL-23 receptor. Epidermal keratinocyte proliferation in psoriasis is activated by T_H17 cells that release IL-17 as well as T_H1 cells that release IFN-γ and tumor necrosis factor. A phase 2a trial showed statistically significant improvement from baseline in the target plaque severity score for tofacitinib ointment 2% (least squares mean, −54.4%) versus vehicle (least squares mean, −41.5%).⁵ Two other phase 2 trials (NCT01246583, NCT00678561) assessing the efficacy, safety, tolerability, and pharmacokinetics of tofacitinib ointment in patients with mild to moderate psoriasis have been completed; results were not available at the time of publication. A phase 2b study that compared 2 dose strengths of tofacitinib ointment—10 mg/g and 20 mg/g—versus placebo over a 12-week period also was completed (NCT01831466); results were not available at the time of publication.

CT327 (Tyrosine Kinase Inhibitor)

CT327 (Creabilis SA) is a tyrosine kinase A (TrkA) inhibitor that affords a novel perspective in the treatment of pruritus by shifting the focus to sensory neurons. In a phase 2b study of 160 patients, a 60% change in the visual analog scale was noted at 8 weeks in the treatment group versus 21% in the placebo group.⁶ Two other phase 2 studies have been completed, one with a cream formulation of pegylated K252a (NCT00995969) and another with an ointment formulation (NCT01465282); results were not available at the time of publication.

DPS-101 (Vitamin D Analogue)

DPS-101 (Dermipsor Ltd) is a combination of calcipotriol and niacinamide. Calcipotriol is a vitamin D₃ analogue that increases IL-10 expression while decreasing IL-8 expression.⁷ It curbs epidermal keratinocyte proliferation by limiting the expression of polo-like kinase 2 and early growth response-1.⁸ It also may induce keratinocyte apoptosis.⁹ Niacinamide is the amide of vitamin B₃ and inhibits proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8.¹⁰ In a dose-response phase 2b trial of 168 patients, DPS-101 demonstrated better results than either calcipotriol or niacinamide alone.¹¹

IDP-118 (Proprietary Steroid and Retinoid Combination)

IDP-118 (Valeant Pharmaceuticals International, Inc) is a combination of halobetasol propionate (HP) 0.01% (a topical corticosteroid) and tazar-otene 0.045% (a selective topical retinoid) in a lotion formulation. In isolation, tazarotene is as effective as a mid to highly potent corticosteroid, but irritation may limit its tolerability. The use of combination treatments of mid to highly potent corticosteroids and tazarotene has shown enhanced tolerability and therapeutic efficacy.¹² Ongoing studies include a phase 1 trial and a phase 2 trial to evaluate low- and high-strength preparations of IDP-118, respectively (NCT01670513). Another phase 2 trial evaluating the efficacy and safety of IDP-118 lotion (HP 0.01% and tazarotene 0.045%) versus IDP-118 monad HP 0.01% lotion, IDP-118 monad tazar-otene 0.045% lotion, and placebo has been completed (NCT02045277); results were not available at the time of publication.

Ruxolitinib (Jak1 and Jak2 Inhibitor)

Ruxolitinib (formerly known as INCB18424)(Incyte Corporation) is a selective Jak1 and Jak2 inhibitor. A phase 2 trial of ruxolitinib showed a 53% decline in the score for mean total lesions in patients treated with ruxolitinib phosphate cream 1% (P=.033) versus 54% in those treated with ruxolitinib phosphate cream 1.5% (P=.056) and 32% in those treated with placebo.¹³ Three other phase 2 studies (NCT00617994, NCT00820950, NCT00778700) have been completed; results were not available at the time of publication.