484 CLINICAL REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor
Gil YOSIPOVITCH 1, Linda F. STEIN GOLD 2, Mark G. LEBWOHL 3, Jonathan I. SILVERBERG 4, Anna M. TALLMAN 5 and Lee T. ZANE 6
1
University of Miami Miller School of Medicine, Miami, FL, 2 Henry Ford Health System, Detroit, MI, 3 Icahn School of Medicine at Mount Sinai, New York, NY, 4 Northwestern University Feinberg School of Medicine, Chicago, IL, 5 Pfizer Inc., New York, NY, and 6 Anacor Pharmaceuticals Inc., acquired by Pfizer Inc., New York, NY, USA
Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild to moderate atopic dermatitis from 2 phase III studies. Patients received crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none( 0) to severe( 3). Early improvement in pruritus required a score of none( 0) or mild( 1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with crisaborole than with vehicle( 56.6 % vs 39.5 %; p < 0.001), including at earliest assessment( day 2, 34.3 % vs 27.3 %; p = 0.013). Crisaborole is a topical treatment option that can rapidly relieve atopic dermatitis-associated pruritus.
Key words: atopic dermatitis; pruritus; crisaborole; phosphodiesterase 4 inhibitor.
Accepted Jan 23, 2018; Epub ahead of print Jan 24, 2018 Acta Derm Venereol 2018; 98: 484 – 489.
Corr: Gil Yosipovitch, MD, Department of Dermatology and Itch Center, University of Miami Hospital, 1600 NW 10th Avenue, Miami, FL 33136, USA. E-mail: yosipog @ gmail. com
Atopic dermatitis( AD) is a chronic inflammatory skin disease that affects approximately 15 – 30 % of children and 2 – 10 % of adults; up to 90 % of cases present as mild or moderate( 1 – 3). Hallmarks of AD include pruritus and pruritus-induced scratching, which lead to exacerbation of symptoms and worsening of disease( 4). Although the pathophysiology behind AD-associated pruritus is under investigation, it is believed to be a complex pathway that involves the interaction of neuropeptides with keratinocytes, immune cells and nerve fibres( 5).
AD-associated pruritus often results in sleep disturbance, psychosocial morbidity and reduced quality of life( QoL) for patients and caregivers. Elevated stress levels and sleep problems can exacerbate pruritus pathways( 4, 6, 7). The“ itch-scratch cycle” describes the pattern of pruritus that leads to scratching, and the scratching that leads to further inflammation( 8). Patients may be unaware they are scratching during sleep, and young patients may additionally experience sleep dysfunction, which can lead to emotional and psychological issues in adolescence( 5, 8). Stress and anxiety have been associated with neuropeptides that can induce further pruritus and subsequent scratching( 5). In addition, the damage to skin because of scratching can lead to skin infection and scarring and possibly contribute to the risk for‘ atopic march’, which is the progression to other atopic diseases, such as allergic rhinitis and asthma( 5, 9, 10). Treatments that provide rapid relief and control of pruritus are important parts of therapy to reduce the occurrence of exacerbation of disease and improve sleep and QoL( 4). Treatment guidelines from the American Academy of Dermatology( AAD) and the American Academy of Allergy, Asthma & Immunology( AAAAI)/ American College of Allergy, Asthma & Immunology( ACAAI) do not provide specific guidance for addressing AD-associated symptoms such as pruritus( 4, 11). However, it is important that therapy reduces pruritus quickly, regardless of disease or pruritus severity or other demographics or characteristics.
Both the AAD and AAAAI / ACAAI guidelines recommend topical pharmacological agents such as topical corticosteroids( TCSs) and topical calcineurin inhibitors( TCIs) to treat AD, while noting the potential of these agents to reduce the severity of pruritus( 4, 11). Although TCIs and TCSs have been shown to reduce the severity of pruritus( 5, 12, 13), they are associated with a range of adverse effects, such as burning and stinging( TCIs) and skin atrophy( TCSs), although skin atrophy is rare with appropriate use of low- or mid-potency TCSs( 4, 11, 14). A boxed warning for TCIs indicates a theoretical risk for malignancy, and superpotent TCSs have been associated with lymphoma( 11, 15). Consequently, additional topical non-steroidal medications are needed that provide rapid relief of pruritus in AD with minimal adverse effects.
Crisaborole ointment is a non-steroidal phosphodiesterase 4( PDE4) inhibitor for the treatment of mild-to-moderate AD( 16). Results of several early phase II trials evaluating crisaborole demonstrated an improvement in pruritus in patients with AD( 17 – 19). Crisaborole was later evaluated in 2 large, identically designed, double-blind, vehiclecontrolled, phase III studies( AD-301: NCT02118766; AD- 302: NCT02118792). In these studies, patients ≥2 years old with mild or moderate AD were randomly assigned 2:1 to receive crisaborole or vehicle ointment twice daily for 28 days( 20). Significantly more crisaborole-treated than vehicle-treated patients achieved the primary endpoint of doi: 10.2340 / 00015555-2893 Acta Derm Venereol 2018; 98: 484 – 489
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.