This page contains a Flash digital edition of a book.
Management


Focus on secukinumab


Here we focus on the pharmacological properties, clinical efficacy and tolerability of this innovative biologic treatment


Richard Langley MD FRCPC Division of Clinical Dermatology and Cutaneous Science, Department of Medicine Dalhousie University, Canada


Secukinumab is a first-in-class fully human monoclonal antibody targeting IL-17A (the central effector cytokine in the immunopathophysiology of psoriasis), and is the first biologic treatment to be approved in the EU for the first-line systemic treatment of moderate to severe plaque psoriasis. The recommended dosage of secukinumab is 300mg administered subcutaneously (sc) at weeks 0–4, followed by 300mg every four weeks.1


It is indicated


for the treatment of psoriasis patients who are candidates for systemic therapy or phototherapy.


Pharmacodynamics/ pharmacokinetics


Secukinumab selectively binds to IL-17A, thereby inhibiting binding at the IL-17 receptor and inhibiting the downstream effects on keratinocytes.1


Serum levels of


total (free and bound) IL-17A are decreased at weeks 4 and 12 following treatment in patients with plaque psoriasis. Following this, there was a slow decrease as a result of reduced clearance of drug-bound IL-17A.


Bioavailability was 55–77% and maximum concentrations in serum were reached six days post-dose. Mean systemic clearance of 0.19l/day and a


Table 1: Summary of Phase III trial results Study


Dosage ERASURE


150mg 300mg Placebo


FIXTURE


150mg 300mg


Etanercept Placebo


FEATURE


150mg 300mg Placebo


JUNCTURE


150mg 300mg Placebo


n


243 245 246


327 327 326 326


59 59 59


61


60 61


Doses of 25–300mg secukinumab sc exhibit dose-proportional pharmacokinetics. Steady-state concentrations were reached after 20–24 weeks.1


mean elimination half-life of 27 days has been observed.1


Efficacy


The efficacy of secukinumab has been investigated in randomised, double-blind, multicentre, placebo-controlled Phase III trials 2–4


:


● FIXTURE (Full Year Investigative Examination of Secukinumab vs Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis)2


● ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis)2


● FEATURE3 ● JUNCTURE.4


Table 1 summarises the results. Recipients received weekly injections of


PASI baseline


22.3 22.5 21.4


23.7 23.9 23.2 24.1


20.5 20.7 21.1


22.0 18.9 19.4


PASI75 week 12


71.6 81.6 4.5


67.0 77.1


44.0 4.9


69.5 75.9 0


71.7 86.7 3.3


PASI90 week 12


39.1 59.2 1.2


41.9 54.2 20.7 1.5


45.8 60.3 0


40.0 55.0 0


PASI: Psoriasis Area and Severity Index; PASI75/90: Reduction of 75/90% from baseline PASI; IGAmod2011: Modified 2011 Investigator’s Global Assessment. www.hospitalpharmacyeurope.com


IGAmod2011 week 12


51.2 65.3 2.4


51.1


62.5 27.2 2.8


52.5 69.0 0


53.3 73.3 0


23


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32