Roflumilast for Chronic Plaque Psoriasis

Abstract

Plaque psoriasis is a multisystem inflammatory disease that affects children and adults. Skin lesions are the most prominent manifestation, appearing as localized or widespread red plaques with silvery scale. Psoriasis may be associated with arthritis, obesity, metabolic syndrome, psychiatric disease, impaired quality of life, and increased risk of cardiovascular disease. 1 The etiology and precise pathogenesis of psoriasis remain unclear. Treatment selection depends on body surface area affected, lesion characteristics (thickness, location), symptoms such as itch and pain, and comorbidities. Topical medications are prescribed in almost all cases, alone or in combination with other therapies. 2 Complex topical regimens using several drugs are often prescribed because different body sites have unique characteristics (skin thickness, hair, skin-to-skin occlusion) that require different vehicle formulations (cream, ointment, oil, foam) and alternating treatment schedules to increase effectiveness and reduce toxicity. 3 As opposed to new systemic agents, few new topical treatments for psoriasis have been identified in the recent past. Prior to 2022, when the US Food and Drug Administration (FDA) approved tapinarof (in May), an aryl hydrocarbon receptor modulating agent for adults, and roflumilast, a PDE4 inhibitor for adults and children 12 years and older (in July), there has not been a new topical mechanism approved for psoriasis in more than a decade. A topical PDE4 inhibitor, crisaborole, and an oral PDE4 inhibitor, apremilast, are currently FDA approved for treatment of atopic dermatitis in patients aged 3 months and older and treatment of psoriasis in patients aged 18 years and older, respectively.In this issue of JAMA, Lebwohl and colleagues 4 present data from the PDE4 Inhibition with Roflumilast for the Management of Plaque Psoriasis (DERMIS-1 and -2) clinical trials. These identically designed, randomized, double-blind, vehicle-controlled phase 3 trials randomized a total of 881 patients to test the safety, efficacy, and patient-reported outcomes of the PDE4 inhibitor roflumilast cream, 0.3%, compared with vehicle, applied once daily to plaque psoriasis for 8 weeks. Participants were aged 2 years and older (mean age, 47.5 years) with plaque psoriasis involving the face, extremities, trunk, or intertriginous areas affecting 2% to 20% of body surface area (BSA) and a minimum of mild disease as defined by the Investigator Global Assessment 5 (IGA) and the Psoriasis Area and Severity Index 6 (PASI). The IGA and PASI are investigator-reported scales used in clinical trials to measure severity and extent from 0 (clear) to 4 (severe) and 0 (no disease) to 72 (maximal disease), respectively. Itch and other patient-reported symptoms and experiences are captured with Worst Itch Numerical Rating Score 7 (WI-NRS) and

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis

“…Some case reports suggested that oral roflumilast may also be beneficial in psoriasis as an alternative systemic treatment, including in comorbidities such as metabolic syndrome or COPD. [51][52][53] The results of a recent company-independent double-blind, placebo-controlled, multicenter, randomized trial (PSORRO) 54 on 46 patients randomized 1:1 to roflumilast or placebo found that over a period of 24 weeks, oral roflumilast proved effective and safe in the treatment of moderate-to-severe plaque psoriasis.…”

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

“…It encompasses four types, each characterized by distinct pathological features and clinical presentations: chronic plaque, pustular, erythrodermic, and articular psoriasis ( 5 , 6 ). Among these, chronic plaque psoriasis (commonly referred to as psoriasis vulgaris) is the most prevalent, accounting for approximately 85-90% of all cases ( 7 – 9 ). Psoriasis has a complicated etiology that involves genetic, epigenetic, and environmental variables ( 10 ).…”

Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)

“… 6 Oral roflumilast was approved first-in-class for treatment of severe COPD more than a decade ago, and generic versions are available in the United States (US). A topical formulation of roflumilast has recently been approved by the US Food and Drug Administration (FDA) for treatment of plaque psoriasis, 7 but the effect of systemic treatment with roflumilast in patients with psoriasis has not been explored.…”