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

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

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

Background: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25hrs by means of membrane-free dermal Open-Flow Microperfusion probes (dOFM) and novel wearable multi-channel pumps. Methods: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 hours from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight Push-Pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis. Results: dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after eight days but did not show significant differences between tissues. On day 8 TNFα release following probe insertion was significantly reduced compared to day 1. Conclusions: Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting