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Secukinumab Distributes into Dermal Interstitial Fluid of Psoriatic Patients as Demonstrated by Open Flow Microperfusion

Calonder, Claudio and Polus, Florine and Woessner, Ralph and Loesche, Christian and Cheng, Yi and Dragatin, Christian and Bodenlenz, Manfred and Aigner, Birgit and Tiffner, K and Mader , J and Ratzer , M and Pieber, Thomas and Bruin, Gerardus and Sinner, Frank (2016) Secukinumab Distributes into Dermal Interstitial Fluid of Psoriatic Patients as Demonstrated by Open Flow Microperfusion. Experimental dermatology, 25 (2). pp. 157-159. ISSN 09066705

Abstract

Secukinumab is a monoclonal antibody targeting IL-17A for treatment of inflammatory diseases, including skin diseases like psoriasis. However, measuring the antibody concentrations at the target site, the skin, still holds challenges with existing methods.
This clinical study (NCT01539213) used the minimally invasive dermal open flow microperfusion (dOFM) method to assess the concentration of secukinumab in the dermal interstitial fluid (ISF). Measurements were performed in the skin of eight healthy subjects and in non-lesional and lesional skin of eight psoriatic subjects after a single 300 mg subcutaneous dose of secukinumab on Day 1. In healthy subjects, the secukinumab concentration in skin on Days 8 and 15 was about 23% of that measured in serum (36.1 and 35.0 µg ml-1 on Days 8 and 15, resp.). Secukinumab concentrations in non-lesional and lesional skin of psoriatic patients were comparable to each other. They were between 28% and 39% of the concentration measured in serum (21.2 µg ml-1). The dermal ISF concentrations obtained from dOFM in healthy subjects is supported by data from punch biopsies and suction blisters.
This study demonstrated that dOFM is a useful technique to assess therapeutic antibody concentrations in the skin. Secukinumab was found in skin rapidly after s.c. injection and achieved levels in the skin sufficient to neutralize free IL-17A locally.

Item Type: Article
Keywords: secukinumab, antibody, psoriasis, dermal open flow microperfusion, suction blister, punch biopsy, No-Net-Flux, interstitial fluid, pharmacokinetics
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/24161

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