An Open Label, Phase 2 Study of MABp1 Monotherapy for the Treatment of Acne Vulgaris and Psychiatric Comorbidity
June 2015 | Volume 14 | Issue 6 | Original Article | 560 | Copyright © June 2015
Daniel Carrasco MD,a Michael Stecher MD,b Gigi Claire Lefebvre MD,c Alan C. Logan ND,d Ronald Moy MDe
aAustin Dermatology Associates, Austin, TX
bXBiotech USA, Austin TX
cMeridien Research, St. Petersburg, FL
dCAMN Research Consulting, Calabasas, CA
eMoy Cosmetic Surgery, Beverly Hills, CA
BACKGROUND: Acne vulgaris is a common inflammatory skin disorder. There remain few rapid, safe, and effective therapy options for patients with moderate to severe acne vulgaris that also address psychological comorbidities such as anxiety.
OBJECTIVE: To assess the efficacy of interleukin 1 alpha blockade in patients with moderate to severe acne vulgaris using the true human monoclonal antibody MABp1.
METHODS: Eleven patients were administered open-label, subcutaneous injections of MABp1 over a six-week period. Objectives were assessment of safety, change in inflammatory lesion count and change in psychosocial functioning using two validated questionnaires.
RESULTS: There were no serious adverse events, or adverse events greater than grade I. Median inflammatory lesion counts decreased 36% (IQR -44% to 1%). Anxiety scores improved (from median 6 to 1) as well as self-image assessment (2.3±0.9 to 2.1±0.1) as measured by the Hospital Anxiety and Depression Scale and the modified Body Image Disturbance Questionnaire.
CONCLUSION: Patients had rapid improvement of skin lesions, as well as psychosocial functioning and anxiety. MABp1 may provide a safe and effective means for treating inflammatory acne lesions and. Further studies using this antibody are warranted in this patient population. J Drugs Dermatol
Acne vulgaris, a common skin disorder affecting more than 40 million persons in the US, with as many as 90% of adolescents suffering from some degree of acne,1 and surveys of adults, place the incidence as high as 26-51% well into the fourth decade.2 Although the precise pathophysiological mechanisms remain obscure, acne is characterized by inflammation of pilosebaceous follicles, which in its most severe form results in cyst and nodule formation leading to permanent scarring.
Aside from the physical features of the disease, acne vulgaris is often associated with significant psychological morbidity3 and in some cases even mortality due to suicide.4 The association of acne and psychological disorders, particularly depression and anxiety, are reportedly more severe in acne patients than in many other serious chronic, nonpsychiatric medical conditions.5
A causal association between acne and psychosocial comorbidities has been suggested in the past. Indeed, almost a century ago it was postulated that a systemic inflammatory response may link acne to other co-occurring disease
processes, including emotional disorders.6 However, a compelling mechanistic link between the seemingly distinct physiological processes has yet to be confirmed by experimental or clinical research.
Previous studies have certainly shed light on the role of inflammation in the acne process. The earliest detectable lesion in the pathogenesis of acne vulgaris is the microcomedone, which is characterized by hypercornification and hyperkeratinization within the pilosebaceous infundibulum and in turn plug formation within the follicle. While the inciting event behind this change in infundibular architecture remains unknown, in vitro experiments have suggested that the inflammatory cytokine IL-1α may play a significant role. Follicles stimulated with IL-1α in vitro have been observed to undergo histologic changes (hypercornification) consistent with those seen in comedone formation, and this effect has been attenuated experimentally via blockade of the IL-1 receptors.7,8
Propionibacterium acnes, a species of bacteria that is commonly associated with the development of acne, has also been shown to stimulate IL-1α production from keratinocytes in vitro,