**10. Declaration of interest**

The authors are employees of Merck Research Laboratories, a division of Merck Sharp and Dohme Corporation, which markets certain topical therapies discussed in the chapter.

#### **11. References**

Bagel J. (2009). Topical therapies for the treatment of plaque psoriasis. *Cutis*, 84, Suppl 4, 3-13.


Topical Therapies for Psoriasis 327

Freeman AK, Linowski GJ, Brady C. (2003). Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. *J Am Acad Dermatol,* 48, 564-568. Fresta M, Puglisi G. (1997). Corticosteroid dermal delivery with skin lipid liposomes. *J* 

Fridman JS, Scherle PA, Collins R, Burn T, Neilan CL, Hertel D, Contel N, Haley P, Thomas B, Shi

Gelfand JM, Shin DB, Neimann AL, Wang X, Margolis DJ, Troxel AB. (2006a). The risk of lymphoma in patients with psoriasis. *J Invest Dermatol,* 126, 10, 2194-2201. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. (2006b). Risk of myocardial infarction in patients with psoriasis. *JAMA*, 296, 14, 1735-1741. Goldberg B, Hartdegen R, Presbury D, Smith EH, Yawalkar S. (1991). A double blind

Gottlieb AB, Ford RO, Spellman MC. (2003). The efficacy and tolerability of clobetasol

Gribetz C, Ling M, Lebwohl M. (2004). Pimecrolimus cream 1% in the treatment of

Guenther LC. (2004). Fixed-dose combination therapy for psoriasis. *Am J Clin Dermatol*, 5, 2,

Guenther LC. (2009). Treatments for scalp psoriasis with emphasis on calcipotriol plus

Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl, M. (2007). Association of patient

Horn EJ, Domm S, Katz HI. (2010). Topical corticosteroids in psoriasis: strategies for

Huang X, Tanojo H, Lenn J, Deng CH, Krochmal L. (2005). A novel foam vehicle for delivery

Jarratt M, Breneman D, Gottlieb AB, Poulin Y, Liu Y, Foley V. (2004). Clobetasol propionate

Katz HI, Prawer SE, Watson MJ. (1989). Mometasone furoate ointment 0.1% vs. hydrocortisone ointment 1.0% in psoriasis. *Int J Dermatol*, 28, 342-344. Kaur I, Saraswat A, Kumar B. (2001). Comparison of calcipotriol and coal tar in conjunction

Kircik L. (2009). Efficacy and safety of topical calcitriol 3 microg/g ointment, a new topical therapy for chronic plaque psoriasis. *J Drugs Dermatol*, 8, Suppl 8, s9-s16. Klaber MR, Hutchinson PE, Pedvis-Leftick A, Kragballe K, Reunala TL, Van de Kerkhof PC,

of topical corticosteroids. *J Am Acad Dermatol*, 53, 1 Suppl 1, S26-38.

reported psoriasis severity with income and employment. *J Am Acad Dermatol*, 57,

shampoo 0.05%: a new option to treat patients with moderate to severe scalp

with sun exposure in chronic plaque psoriasis: a pilot study. *J Dermatol*, 28, 448-450.

Johnsson MK, Molin L, Corbett MS, Downess N. (1994). Comparative effects of

betamethasone dipropionate gel (Xamiol). *Skin Therapy Lett*, 14, 1-4. Gupta AK, Ryder JE. (2003). Photodynamic therapy and topical aminolevulinic acid: an

improving safety. *J Eur Acad Dermatol Venereol*, 24, 119-124.

in cutaneous inflammation. *J Invest Dermatol*. (Epub ahead of print).

J, Collier P, Rodgers JD, Shepard S, Metcalf B, Hollis G, Newton RC, Yeleswaram S, Friedman SM, Vaddi K. (2011). Preclinical evaluation of local JAK1 and JAK2 inhibition

multicenter comparison of 0.05% halobetasol propionate ointment and 0.05% clobetasol propionate ointment in patients with chronic localized plaque psoriasis. *J* 

propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis

intertriginous psoriasis: a double-blind, randomized study. *J Am Acad Dermatol*, 51,

*Control Rel,* 44, 141-151.

*Am Acad Dermatol*, 25, 6, 1145-1148.

731-738.

6, 963-971.

71-77.

of nonscalp regions. *J Cutan Med Surg*, 7, 185-192.

overview. *Am J Clin Dermatol*, 4, 699-708.

psoriasis. *J Drugs Dermatol*, 3, 367-373.

Beani C. (2002). Salicylic acid as a keratolytic agent. *Ann Dermatol Venereol*. 2002, 129, 6, 933-935.


Beani C. (2002). Salicylic acid as a keratolytic agent. *Ann Dermatol Venereol*. 2002, 129, 6, 933-935. Beck LA. (2005). The efficacy and safety of tacrolimus ointment: a clinical review. *J Am Acad* 

Bernhard J, Whitmore C, Guzzo C, Kantor I, Kalb RE, Ellis C, Urbach F, Schwartzel EH,

Bhutani T, Zitelli KB, Koo J. (2011). Yin-yang strategy: proposing a new, effective, repeatable, sequential therapy for psoriasis. *J. Drug Dermatol*, 10, 831-834. Bissonnette R, Nigen S, Bolduc C. (2008). Efficacy and tolerability of topical tacrolimus ointment for the treatment of male genital psoriasis. *J Cutan Med Surg*, 12, 230-234. Blum G, Yawalkar S. (1991). A comparative multicenter double blind trial of 0.05%

Bowman PH, Maloney JE, Koo JY. (2002). Combination of calcipotriene (Dovonex) ointment

Boyrke JF, Berth-Jones J, Hutchinson PE. (1993). Occlusion enhances the efficacy of topical calcipotriol in treatment of psoriasis vulgaris. *Clin Exp Dermatol*, 18, 504-506. Bressinck R, Williams J, Peets E. (1988). Comparison of effect of mometasone furoate

Brodell RT, Bruce S, Hudson CP, Weiss JS, Colon LE, Johnson LA, Gottachalk RW. (2011). A

De Jong EMGJ, Mørk NJ, Seijger MM. (2003). The combination of calcipotriol and

multicentre placebo controlled randomized trial. *Br J Dermatol*, 148, 318-325. Douglas WS, Poulin Y, Decroix J. (2002). A new calcipotriol/betamethasone formulation

Fabroni C, Lotti T. (2009). Pimecrolimus in dermatology. *G Ital Dermatol Venereol*, 144, 321-325. Feldman SR, Ravis SM, Fleischer AB. (2001). Betamethasone valerate in foam vehicle is

Feldman SR, Yentzer BA. (2009). Topical clobetasol propionate in the treatment of psoriasis:

Franz TJ, Parsell DA, Halualani RM, Hannigan JF, Kalbach JP, Harkonen WS. (1999).

the treatment of scalp psoriasis. *J Cutan Med Surg*, 5, 386-389.

a review of newer formulations. *Am J Clin Dermatol*, 10, 397-406.

psoriasis: a pilot study. *J Am Acad Dermatol*, 46, 907-913.

psoriasis patients. *Today's Ther Trends*, 5, 4, 25-35.

Gibson JR. (1991). Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies. *J Am* 

halobetasol propionate ointment and 0.1% betamethasone valerate ointment in the treatment of patients with chronic localized plaque psoriasis. *J Am Acad Dermatol*,

and tazarotene (Tazorac) gel versus clobetasol ointment in the treatment of plaque

ointment 0.1%, and hydrocortisone ointment 1%, on adrenocortical function in

multi-center, open-label study to evaluate the safety and efficacy of a sequential treatment regimen of clobetasol propionate 0.05% spray followed by calcitriol 3 mg/g ointment in the management of plaque psoriasis. *J Drugs Dermatol*, 10, 2, 158-164. Campalani E, Barker J.N. (2005). The clinical genetics of psoriasis. *Current Genomics,* 6, 51-60. Claréus BW, Houwing R, Sindrup JH, Wigchert S. (2009). The DESIRE study - psoriasis

patients' satisfaction with topical treatment using a fixed combination of calcipotriol and betamethasone dipropionate in daily clinical practice. *Eur J* 

methotrexate compared with methotrexate and vehicle in psoriasis: results of a

with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris. *Acta Derm Venereol*, 82, 131-135.

effective with both daily and twice a day dosing: a single-blind, open-label study in

Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and

*Dermatol*, 53, 2 Suppl 2, S165-S170.

*Acad Dermatol,* 25, 1170-1174.

25, 1153-1156.

*Dermatol*, 19, 581-585.

efficacy. *Int J Dermato,* 38, 628-632.


Topical Therapies for Psoriasis 329

Mesa RA. (2010). Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of

Mraz S, Leonardi C, Colón LE. (2008). Different treatment outcomes with different

Muller K, Bendtzen K. (1996). 1,25-dihydroxyvitamin D3 as a natural regulator of human

Nast A, Kopp I, Augustin M. (2007). German evidence-based guidelines for the treatment of

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

Nguyen T, Gattu S, Pugashetti R, Koo J. (2009). Practice of phototherapy in the treatment of

Norris DA. (2005). Mechanisms of action of topical therapies and the rationale for

Papp KA, Guenther L, Boyden B, et al. (2003). Early onset of action and efficacy of a

Papp KA, Carey W. (2010). Psoriasis care: new and emerging pharmacologic trends. *J Cutan* 

Pathirana D, Ormerod AD, Saiag P, Smith C, Spuls PI, Nast A, Barker J, Bos JD, Burmester GR,

combination of calcipotriene and betamethasone dipropionate in the treatment of

Chimenti S, Dubertret L, Eberlein B, Erdmann R, Ferguson J, Girolomoni G, Gisondi P, Giunta A, Griffiths C, Hönigsmann H, Hussain M, Jobling R, Karvonen SL, Kemeny L, Kopp I, Leonardi C, Maccarone M, Menter A, Mrowietz U, Naldi L, Nijsten T, Ortonne JP, Orzechowski HD, Rantanen T, Reich K, Reytan N, Richards H, Thio HB, van de Kerkhof P, Rzany B. (2009). European S3-Guidelines on the systemic treatment of psoriasis vulgaris. *J Eu Acad Dermatol Venereology*, 23, Suppl 2, 5-70. Prakash A, Benfield P. (1998). Topical Mometasone: A Review of its pharmacological

properties and therapeutic use in the treatment of dermatological disorders. *Drugs*,

Rivera AM, Hsu S. (2005). Topical halobetasol propionate in the treatment of plaque

Ruzicka T. (2006). Methylprednisolone aceponate in eczema and other inflammatory skin

Saraceno R, Gramiccia T, Frascione P, Chimenti, S. (2009). Calcipotriene/betamethasone in the treatment of psoriasis: a review article. *Expert Opin Pharmacother*, 10, 14, 2357-2365. Staberg B, Roed-Petersen J, Menne T. (1989). Efficacy of topical treatment in psoriasis with

Stein LF, Sherr A, Solodkina G, Gottlieb AB, Chaudhari U. (2001). Betamethasone valerate foam for treatment of nonscalp psoriasis. *J Cutan Med Surg,* 5, 4, 303-307. Su Y-H, Fang J-Y. (2008). Drug delivery and formulations for topical treatment of psoriasis.

MC903, a new vitamin D analogue. *Acta Derm Vevereol,* 69, 147-150.

myeloproliferative neoplasms and psoriasis. *IDrugs*, 13, 6, 394-403.

psoriasis vulgaris (short version). *Arch Dermatol Res,* 299, 111–138.

Nestle FO, Kaplan DH, Barker J. (2009). Psoriasis. *New Engl J Med,* 361, 496-509.

moderate-to-severe psoriasis. *Curr Probl Dermatol,* 38, 59-78.

psoriasis. *J Am Acad Dermatol*, 48, 48-54.

psoriasis: a review. *Am J Clin Dermatol,* 6, 311-316.

*Exp Opin Drug Deliv*, 5, 235-249.

disorders-a clinical update. *Int J Clin Pract*, 60, 85–92.

*Med Surg*, 14, 3, 119-129.

55, 145-163.

combination therapy. *J Am Acad Dermatol*, 53, 1 Suppl 1, S17-S25.

immune functions. *J Invest Dermatol Symp Proc*, 1, 1, 68-71.

therapies. *J Am Acad Dermatol,* 60, 4, 643-659.

*Dermatolog Treat*, 19, 354-359.

Guidelines of care for the management and treatment of psoriasis with topical

formulations of clobetasol propionate 0.05% for the treatment of plaque psoriasis. *J* 

calcipotriol solution (50 micograms/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis. *Br. J. Dermatol*, 131, 5, 678-683.


mg/ml) in the treatment of scalp psoriasis. *Br. J. Dermatol*, 131, 5, 678-683. Koo J. (1999). Systemic sequential therapy of psoriasis: A new paradign for improved

Korting HC, Zienicke H, Schäfer-Korting M, Braun-Falco O. (1990). Liposome encapsulation

Kowalzick L. (2009). Novel topical therapy for mild-to-moderate plaque psoriasis: focus on

Lebwohl M, Peets E, Chen V. (1993). Limited application of mometasone furoate on the face

Lebwohl M, Ast E, Callen JP, Cullen SI, Hong SR, Kulp-Shorten CL, Lowe NJ, Phillips TJ,

Lebwohl M, Menter A, Koo J, Feldman SR. (2004). Combination therapy to treat moderate to

Lebwohl M, Menter A, Weiss J, Clark SD, Flores J, Powers J, Balin AK, Kempers S, Glinert

Lehmann B. (2009). Role of the vitamin D3 pathway in healthy and diseased skin-facts,

Linden KG, Weinstein GD. (1999). Psoriasis: current perspectives with emphasis on

Long CC, Mills CM, Finlay AY. (1998). A practical guide to topical therapy in children. *Br J* 

Luger T, Paul C. (2007). Potential new indications of topical calcineurin inhibitors.

Martín Ezquerra G, Sánchez Regaña M, Herrera Acosta E. (2006). Topical tacrolimus for the

Mason AR, Mason J, Cork M. (2009). Topical treatments for chronic plaque psoriasis.

Maurer TA. (2005). Dermatologic manifestations of HIV infection. *Top HIV Med*, 13, 5, 149-154. Medansky RS, Brody NI, Kanof NB. (1987). Clinical investigations of mometasone furoate – a novel nonfluorinated, topical corticosteroid. *Semin Dermatol*. 6, 2, 94-100. Medansky RS, Bressinck R, Cole GW. (1988). Mometasone furoate ointment and cream 0.1%

ointment in chronic plaque psoriasis. *J Am Acad Dermatol,* 25, 1166-1169. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY,

treatment of psoriasis on the face, genitalia, intertriginous areas and corporal

in treatment of psoriasis: comparison with ointment and cream formulations of flucinolone acetonide 0.025% and triamcinolone acetonide 0.1%. *Cutis*. 42, 480-485. Mensing H, Korsukewitz G, Yawalkar S. (1991). A double blind multicenter comparison of

0.05% halobetasol propionate ointment and 0.05% betamethasone dipropionate

Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R. (2009). Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3.

therapeutic results. *J. Am. Acad. Dermatol*, 41, S25-28.

psoriasis vulgaris. *Eur J Clin Pharmacol,* 39, 4, 349-351.

calcitriol. *Clin Cosmet Investig Dermatol*, 16, 2, 153-159.

psoriasis. *J Am Acad Dermatol,* 38, 5, 705-711.

*Drugs Dermatol*, 6, 4, 428-435.

*Dermatol*,138, 293-296.

treatment. *Am J Med*, 107, 595-605.

*Dermatology*, 215, Suppl 1:45-54.

plaques. *J Drugs Dermatol*, 5, 334-336.

*Cochrane Database Syst Rev*, 2, CD005028.

severe psoriasis. *J. Am. Acad. Dermatol*, 50, 416-430.

contradictions and hypotheses. *Exp Dermatol*, 18, 97-108.

calcipotriol solution (50 micograms/ml) and betamethasone 17-valerate solution (1

improves efficacy of betamethasone dipropionate in atopic eczema but not in

and intertriginous areas: analysis of safety and efficacy. I*nt J Dermato*l, 32, 11, 830-831.

Rosen T, Wolf DI, Quell JM, Sefton J, Lue JC, Gibson JR. (1998). Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque

RJ, Fleming T, Liu Y, Graeber M, Pariser DM. (2007). Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies. *J*  Guidelines of care for the management and treatment of psoriasis with topical therapies. *J Am Acad Dermatol,* 60, 4, 643-659.


**1. Introduction** 

**2. TNF Inhibitors** 

 \*

evaluation for the treatment of both diseases.

Roberto Giacomelli3, Francesca Zazzeroni1 and Edoardo Alesse1 *1Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy* 

<sup>2</sup>*Department of Sciences and Biomedical Technology, University of L'Aquila, L'Aquila, Italy*  3*Department of Internal Medicine and Public Health, University of L'Aquila, L'Aquila, Italy*

**16** 

 *Italy* 

Daria Capece et al.\*

*Department of Experimental Medicine, University of L'Aquila, L'Aquila* 

**Biotech on the Rise: The Treatment** 

Psoriasis is a chronic inflammatory skin disorder affecting 1–3% of the general population worldwide. Up to one-third of psoriatic patients have concomitant psoriatic arthritis (Gerdes et al, 2009). Multiple studies and clinical trials support an important role for dysregulation of the immune system in the development of psoriasis. In recent years, the improved understanding of the molecular basis underlying psoriasis has led to the introduction of biological drugs, providing a new effective treatment option for this disease. Biologics target key steps in the pathogenesis of psoriasis, and can be classified into three main categories: TNF inhibitors, T cell inhibitors and IL-12/IL-23 inhibitors (Weger, 2010). In this chapter we discuss the state of the art of biological therapies for psoriasis and psoriatic arthritis and give a brief overview of the new biological approaches that are currently undergoing

TNF is a proinflammatory cytokine that plays key roles in both innate and adaptive immunity. At high concentrations, it can trigger an excessive inflammatory response ending in organ damage. The development of anti-TNF biologics originated from a study by Brennan et al., which showed that the expression of pro-inflammatory cytokines by synoviocytes in rheumatoid arthritis patients was inhibited by TNF-neutralizing antibodies (Brennan et al, 1989). To date, the role of TNF in psoriasis and psoriatic arthritis has been fully investigated (Schottelius et al, 2004). Increased levels of TNF and a differential expression of TNF receptors I and II have been found in lesional psoriatic skin compared with normal-appearing skin; in addition, in psoriatic patients, the plasma concentration of TNF is higher and the mRNA expression of this cytokine is increased in peripheral blood

Valeria Iansante1, Mariafausta Fischietti1, Daniela Verzella1, Maria Concetta Fargnoli2, Ketty Peris2,

**of Psoriasis with Biological Drugs** 

