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 .