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Current Therapies for Psoriasis, Part 1

Current Therapies for Psoriasis, Part 1

The rapid changes in the treatment of psoriasis have provided many new options for the approximately 7.5 million Americans who live with psoriasis, of whom 30% may also develop psoriatic arthritis (PsA).1 The tremendous variation in psoriasis—with common, guttate, inverse, pustular, and erythrodermic variants as well as variation in the parts of the body affected by the disease—complicates the treatment decision. Psoriasis not only has a large direct effect on patients’ quality of life; psoriasis is associated with many comorbidities such as obesity, cardiovascular disease, diabetes, and depression. 

The development of new targets for psoriasis treatments have paralleled our growing understanding of immunological pathways involved in the pathogenesis of psoriasis. Our improved understanding of the human factors that contribute to how well people use their medications has also led to major improvements in our ability to control the disease. With new evolving information, both topical and systemic medications, have been developed to selectively take advantage of these developments.2 

There are a few basic steps in the treatment of psoriasis. First is to address the psychosocial and educational needs of patients with psoriasis. A straightforward way to do this is to encourage patients to join and make use of resources from the National Psoriasis Foundation. This Foundation offers patients a host of materials on how to manage the disease and the social implications of having psoriasis.

The next step in psoriasis treatment is to assess for comorbidities that affect treatment choices. Assessment for PsA is essential, as the skin involvement typically occurs before joint disease, and early identification and treatment of joint involvement may help prevent the occurrence of irreversible joint destruction.

Finally, a key step in psoriasis treatment is to define whether the patient has mild to moderate psoriasis that can be treated with topical treatments alone or whether the patient has moderate to severe disease that will require phototherapy or systemic treatments. In clinical trials, when 10% or more of the body surface area is involved, the patient is generally considered to have moderate to severe disease. In clinical practice, a functional definition is typically used: Can patients reasonably and effectively use topical treatment to treat the psoriasis? If so, then they are treated with topical treatments (and/or localized UV treatments), and if not, then they can be started directly on phototherapy or systemic treatment (Figure).

figure 1
Figure. Psoriasis Treatment Algorithm

Topical Therapies

Topical treatments are indicated for mild to moderate psoriasis and for localized resistant areas of disease in patients concomitantly using phototherapy or taking systemic medications. There are many options available (Table 1), and the majority of topical medications work by decreasing the amount of inflammation and/or modulating keratinocyte differentiation. Topical medications work well for patients who are compliant and willing to apply their medication on a regular basis. The main topical medications utilized are corticosteroids with or without a concomitant vitamin D3 analog. Topical calcineurin inhibitors are also valuable, particularly for the face and intertriginous involvement.3 

Table 1

Topical Corticosteroids

Corticosteroids are the mainstay of topical therapy for psoriasis. They come in many vehicle formulations including ointments, creams, lotions, solutions, foams, shampoo, oil, and sprays. Traditional dogma was that ointments are generally preferred for dry, scaly psoriasis lesions because ointments are more potent than other vehicles and because moisturizing the plaque with an ointment vehicle has direct benefits; but due to the greasy, messy nature of ointments, patients may prefer a cream or lotion that is easier to use. The ability to find a formulation the patient will actually use is critical when selecting any topical agent. 

Different vehicles and different strengths of corticosteroid may be used for different parts of the body. Sprays and solution vehicles are normally prescribed for lesions on the scalp because they are able to penetrate past the hair. Potent corticosteroids—such as clobetasol proprionate, fluocinonide, and betamethasone diproprionate—are commonly prescribed for thick plaques located on the trunk and extremities, while moderate potency corticosteroids, like triamcinolone acetonide, are used for thinner and more sensitive areas of involvement. For the most sensitive areas, such as the face and intertriginous areas, mild to moderate potency steroids, such as hydrocortisone, can be effective. The use of different vehicles and different strengths of corticosteroids allows physicians to tailor the treatment to the needs of different lesions, but giving patients too many treatments may complicate the regimen and adversely affect patients’ use of the treatments. Where possible, choosing a single vehicle and corticosteroid that can be used for all the lesions (for example, using a high-potency agent and just reducing the duration of use in sensitive areas) may be best.

These medications can be used once or twice daily for 2 to 4 weeks continuously at a time, followed by intermittent use as needed. Patients can experience rapid improvement with topical corticosteroids, but using them continuously for an extended period of time can have unwanted side effects, including skin atrophy, striae, hypopigmentation, steroid acne, and miliaria.3,4

Intralesional corticosteroid injections can also be used for very localized, recalcitrant plaques, particularly when there is a superimposed prurigo component caused by extensive picking, scratching, or rubbing the lesion. Triamcinolone acetonide (Kenalog) suspension (at 10 mg/mL diluted with sterile saline to 2.5-5 mg/mL) can be injected directly into a plaque at 1 month intervals in order to decrease the thickness.4

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Vitamin D3 Analogs

Vitamin D, naturally absorbed from the diet or synthesized in the skin after exposure to sunlight, plays a role in epidermal proliferation and differentiation. Vitamin D can promote keratinocyte proliferation at a low concentration or inhibit proliferation at a high concentration through a dose-dependent process. Vitamin D3 analogs, such as calcipotriene (Dovonex) and calcitriol (Vectical), have had success in treating psoriasis as a corticosteroid-sparing agent. They come in ointment, cream, and solution formulations and are useful for maintenance therapy when the patient is not using a topical corticosteroid. They can be prescribed for twice-daily application; response to therapy is considerably slower compared with corticosteroids. Common side effects are temporary irritation, burning, pruritus, and sensitivity to sunlight. A rare but severe side effect is serum elevation of calcium seen only with extensive use of large areas of the body. A combination product containing both a vitamin D analog and a topical corticosteroid, such as calcipotriene and betamethasone dipropionate (Taclonex), can provide another option with greater efficacy (perhaps because of better adherence to 1 product than to 2) and fewer side effects.3-5

Topical Calcineurin Inhibitors

Calcineurin inhibitors are less commonly prescribed for psoriasis but offer a topical alternative for thin plaques in areas prone to corticosteroid side effects. The 2 currently available, tacrolimus 0.1% (Protopic) and pimecrolimus 1% (Elidel), are corticosteroid-sparing agents that provide an anti-inflammatory effect. They are particularly useful for sensitive areas prone to side effects from corticosteroids, such as the face and intertriginous areas. Disadvantages of using these medications include that they are slower to provide relief compared with topical corticosteroids and can cause temporary burning and pruritus after application. This can be avoided with prior corticosteroid use and application to dry skin.3,4,6 While topical calcineurin inhibitors carry a black box warning for lymphoma, extensive data finds no increased risk for lymphoma or skin cancer.7-9

Tazarotene

Tazarotene (Tazarac) is a topical retinoid that is indicated for acne vulgaris and plaque psoriasis. It binds to retinoic acid receptors in the skin and modulates keratinocyte hyperproliferation and differentiation. Topical tazarotene comes in gel formulations of 0.05% and 0.1% and is indicated for once-daily use. The 0.1% gel is somewhat more effective than the 0.05% gel, but it has a higher rate of irritation. Concomitant use with corticosteroids mitigates the irritation. In addition, tazarotene is contraindicated in women who are pregnant due to a theoretical risk of birth defects.3,4,6

Anthralin

Although in the past a commonly prescribed topical medication, anthralin is rarely used today for treating psoriasis. Anthralin possesses anti-inflammatory and antiproliferative effects on keratinocytes by decreasing neutrophil superoxide generation and inhibiting monocyte-derived IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Currently, it is not often perscribed due to its tendency to be very irritating and because it also stains the skin, clothing, bedding, and even ceramic bathroom fixtures.3,4

Tar

Tar derived from both coal and wood (such as pine, birch, and juniper) has been used for more than a century as an effective over-the-counter treatment for psoriasis. It is typically sold in oil and shampoo formulations, but tar is not commonly used today. Due to their strong odor and ability to stain clothing, many patients prefer other topical therapies.3,4

Salicylic Acid 

Salicylic acid is an over-the-counter keratolytic agent that is found in shampoos, creams, solutions, and gels for the treatment of mainly acne and psoriasis. It can help promote the absorption of other topical medications like corticosteroids; however, it is not commonly prescribed by physicians because current therapies are more effective.3,4 Moreover, complicating treatment regimens with penetration enhancers like salicylic acid may needlessly complicate the treatment regimen and compromise patients’ adherence to treatment.

Phototherapy

Phototherapy involves exposing the skin to UV light over a period of multiple sessions. It is one of the oldest treatments used in dermatology and is still effective at treating inflammatory skin disorders such as eczema, vitiligo, and psoriasis. Although its use over the past few decades has been declining, it can still be a cost-effective treatment indicated for moderate to severe psoriasis (psoriasis that affects greater than 10% of the body surface area) as well as a useful approach for treating limited disease. Multiple mechanisms for phototherapy’s mechanism of action in psoriasis have been hypothesized, including causing local immunosuppression and apoptosis of keratinocytes and T cells in the epidermis and dermis. For psoriasis, UV wavelengths of light (including 296, 300, 304, and 313 nm) can clear psoriasis plaques; therefore, fluorescent bulbs and other devices have been manufactured to produce these wavelengths. There are different types of phototherapy (Table 2) used in dermatology for treating psoriasis including broadband UV-B (BB-UVB, 280-320 nm), narrowband UV-B (NB-UVB, 311-313 nm), psoralen–UV-A (PUVA, 320-400 nm), and the excimer laser (UV-B at 308 nm).3,4,10

Table 2

NB-UVB

NB-UVB has largely replaced BB-UVB due to its ability to emit a more specific wavelength making it more effective at treating psoriasis. It is administered either in the office or in-home phototherapy units and the amount given is based on the patient’s Fitzpatrick skin type and/or their minimal erythema dose (the shortest amount of NB-UVB to induce erythema at 24 hours). The patients are typically treated 3 to 4 times per week for a few weeks at a time. Side effects are erythema, pruritus, phototoxicity, photoaging, and perhaps some increased risk of nonmelanoma skin cancers.3,4,10 

PUVA

PUVA is the process in which the patient takes 8-methoxypsoralen, a photosensitizing medication, either orally or applied topically prior to UV-A exposure. The psoralen enters cells, intercalates into the DNA, and cross links the DNA when exposed to UV light. Patients generally receive between 20 to 30 treatments administered 2 to 3 times per week. PUVA works especially well for palmoplantar psoriasis due to its deeper penetration compared with UV-B. Although it is a highly effective form of phototherapy, PUVA also has the most side effects including erythema, pruritus, phototoxicity, headaches, cataracts, insomnia, nausea, photoaging, melanoma, and a definite increase in the risk of nonmelanoma skin cancers.3,4,10

Excimer Laser

The excimer laser is primarily used to treat localized plaques and allows nonaffected skin to be spared. Most patients clear in less than 10 to 20 treatments, depending on the disease and the aggressiveness of the dosing schedule. Side effects observed are erythema, blisters, and hyperpigmentation, but these are generally well tolerated because only the lesions (and not the entire body surface) are exposed and affected. Nonlaser devices that deliver localized UV treatment are also available.3,4,10

Systemic Therapies

Systemic therapy is indicated for patients with moderate to severe psoriasis, for those with PsA, and in patients who are unresponsive to other forms of therapy.  About one-third of all patients with psoriasis require treatment with systemic medications; only about 5% of people with psoriasis have disease of that level of severity (most people with psoriasis are not patients, and the ones who are tend to be ones with more severe disease). Systemic medications generally work by modulating the immune response. Systemic treatments are considered as those given orally and those given by injection. The oral agents include several older medications—methotrexate, acitretin (Soriatane), and cyclosporine—and the newer agent apremilast (Otezla). Injectables include a long and growing list of biologics. Oral agents are often preferred by patients over taking an injection; however, the injectable treatments provide higher efficacy and better safety. Another limitation of injectable biologic medications is their greater immunogenicity compared with small molecule drugs and associated loss of efficacy over time; a limitation of the oral agents is that they often have adverse effects beyond their effects on the immune system.2

 

Dr Glass is with the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC. She received her medical degree at the Edward Via College of Osteopathic Medicine in Blacksburg, VA. She completed a traditional rotating internship at Sampson Regional Medical Center and is currently a resident in dermatology at North Fulton Hospital in Roswell, GA.

Dr Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology, and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.

Disclosure: Dr Glass reports no relevant financial relationships. The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P.

Dr Feldman is a consultant and/or speaker for Amgen, Abbvie, Abbott Labs, Advanced Medical, BiogenIdec, Bristol-Myers Squibb, Caremark, Galderma, Genentech, Janssen, Pfizer Inc, Photomedex, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, Taro,and Warner Chilcott.  Dr Feldman has received grants from Abbott Labs, Abbvie, Amgen, Anacor, Astellas, Aventis Pharmaceuticals, Basilea, BiogenIdec, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Genentech, Gerson Lehrman Group, Guidepoint Global, HanAll Pharmaceuticals, Janssen, Kikaku, Leo Pharma Inc, Medicis, Merck & Co., Inc, Mylan, Novartis, Ortho Pharmaceuticals, Photomedex,  Pharmaderm,  Pfizer Inc, Regeneron, Roche Dermatology, 3M, Sanofi, Sienna, Stiefel/GlaxoSmithKline, Sun Pharma, Suncare Research, Taro, Valeant, Warner Chilcott, and Xenoport, and he has received stock options from Photomedex. He receives royalties from Informa, UptoDate, and Xlibis. He is owner of www.DrScore.com and a founder of Causa Research.

References

1. Fact sheet library. National Psoriasis Foundation website. https://www.psoriasis.org/publications/patient-education/fact-sheets. Accessed June 15, 2017.

2. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Sem Immunopathol. 2016;38(1):11-27.

3. Farhangian ME, Anderson KL, Feldman SR. Practical Psoriasis Management. Winston-Salem, NC: Steven R. Feldman; 2015.

4. James WD, Berger TG, Elston DM. Seborrheic dermatitis, psoriasis, recalcitrant palmoplantar eruptions, pustular dermatitis, and erythroderma. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin. 12th ed. Philadelphia, PA: Elsevier. 2016:85-198. 

5. Trémezaygues L, Reichrath J. Vitamin D analogs in the treatment of psoriasis: Where we are standing and where we will be going? Dermatoendocrinol. 2011;3(3):180-186.

6. Feldman SR. Treatment of psoriasis. UpToDate. http://www.uptodate.com/contents/treatment-of-psoriasis. Updated May 25, 2017. Accessed June 15, 2017.

7. Margolis DJ, Abuabara K, Hoffstad OJ, Wan J, Raimondo D, Bilker WB. Association between malignancy and topical use of pimecrolimus. JAMA Dermatol. 2015;151(6):594-599. 

8. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology. 2007;214(4):289-295. 

9. Callen J, Chamlin S, Eichenfield LF, et al. A systematic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol. 2007;156(2):203-221. 

10. Nakamura M, Farahnik B., Bhutani T. Recent advances in phototherapy for psoriasis. F1000Res. 2016;5(F1000 Faculty Rev):1684. doi: 10.12688/f1000research.8846.1

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