A Major Win for the Treatment of Nail Psoriasis

Psoriasis is a chronic systemic inflammatory disease involving the skin, nails, and joints. In patients with cutaneous psoriasis, the prevalence of nail psoriasis is greater than 50%.¹ Furthermore, nail psoriasis affects 80-90% of psoriasis patients during their lifetime.² While most patients have concurrent skin and nail disease, 5-10% have isolated nail psoriasis,³ presenting with pitting, leukonychia, red spots in the lunula, and Beau’s line, when the inflammation affects the nail matrix. Inflammation of the nail bed presents with subungual hyperkeratosis, onycholysis, salmon patches, oil spots, and splinter hemorrhages in the nail.¹ Nail psoriasis is also highly associated with psoriatic arthritis, which if severe and progressive, can lead to debilitation. In patients with psoriatic arthritis, nail involvement approaches 70%. Furthermore, studies have shown that the presence of nail psoriasis may predict development of psoriatic arthritis later in life.⁴ Studies have also shown that patients with psoriasis are more likely to also have onychomycosis, further worsening their nail disease.^5,6 Psoriatic nails are not just an aesthetic concern. They can be painful, making it difficult to perform activities of daily life such as tying shoes or buttoning a shirt. Nail psoriasis may also contribute to social stigmatization and patients may have trouble with employment and with personal interactions. Numerous studies have shown that nail psoriasis has a significant impact on quality of life.^7-9 Given the extensive symptoms, sequelae, systemic manifestations, and impact on quality of life, it is not surprising that in a survey-based study, 47% of patients with nail psoriasis expressed the desire to be treated for their disease.¹⁰ While nail psoriasis is a common and important disease, there is a paucity of randomized controlled trials that are specifically focused on nail psoriasis to guide treatment plans. Topical treatments including high-potency topical corticosteroids, tazarotene, or calcipotriol may be good options for patients with mild nail disease, but penetration is inadequate with hyperkeratotic nails. In addition, application of the medication one to two times daily for extended periods of time may limit patient compliance. Monthly intralesional corticosteroids are effective, but this treatment works better for matrix disease than bed disease and adherence may be diminished by the frequency and pain associated with injections. Oral methotrexate is another option for nail psoriasis, but nail matrix disease generally responds better nail bed disease.^11,12 In addition, efficacy is significantly less than that of most biologics.13 Oral acitretin is moderately effective for both matrix and bed disease, but improvement in nail bed in ammation is typically slow.^12-14 Oral apremilast shows some efficacy in nail matrix and bed psoriasis at 16 weeks with larger improvements seen at 32 weeks.^15-17 Biologics have revolutionized the treatment of psoriasis and psoriatic arthritis and are the most effective agents for treating psoriatic nail disease. The inflammation can be suppressed with anti-TNFα, as well as anti-IL-17 and anti-IL-12/23 monoclonal antibodies.¹⁸ Clinical improvements in nail disease typically lag behind skin disease, but efficacy in nail psoriasis can be seen at 12 weeks with additional improvements or even completely normal nails seen at 1 year. Numerous studies have shown that conventional therapies are likely less effective and slower-acting therapies than biologics in treating nail disease. Does the presence of nail psoriasis alone justify the use of biologic therapies that are expensive, may require frequent injections, and may be associated with side effects? In 2015, the Medical Board of the National Psoriasis Foundation developed treatment guidelines for nail psoriasis to assist dermatologists in caring for their patients. These recommendations took into account severity of skin disease, psoriatic arthritis, nail disease, and impairment of quality of life. In sum, they suggested high-potency topical corticosteroids with or without calcipotriol for patients with nail psoriasis only. However, if this initial treatment was ineffective, they recommended adalimumab, etanercept, intralesional corticosteroids, ustekinumab, methotrexate sodium, and acitretin.¹⁹ Despite mounting evidence that biologics provide the fastest and most ef cacious for nail psoriasis, it remains challenging for patients to get access to these medications, often requiring concomitant skin and/or joint involvement. Dermatologists are faced with settling for less desirable treatment options, and the disease often progresses leaving patients with loss of functionality, permanent nail dystrophy, and a negative impact on quality of life. On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved the inclusion of moderate to severe ngernail psoriasis data in the adalimumab prescribing information for patients with moderate to severe chronic plaque psoriasis.²⁰ The FDA based this decision on data from a multicenter, double-blind, randomized, parallel-arm, placebo-controlled, Phase 3 clinical trial (NCT02016482) that evaluated the safety and efficacy of adalimumab for the treatment of nail psoriasis in patients with