Secukinumab Improves Physical Function in Subjects With Plaque Psoriasis and Psoriatic Arthritis: Results from Two Randomized, Phase 3 Trials
August 2015 | Volume 14 | Issue 8 | Original Article | 821 | Copyright © 2015
Alice B. Gottlieb MD PhD,a Richard G. Langley MD,b Sandra Philipp MD PhD,c Bardur Sigurgeirsson MD PhD,d Andrew Blauvelt MD MBA,e Ruvie Martin PhD,f Charis Papavassilis MD PhD,g and Shephard Mpofu MDg
aTufts Medical Center, Boston, MA,
bDalhousie University, Halifax, Canada
cCharité Universitätsmedizin, Berlin, Germany
dUniversity of Iceland, Reykjavik, Iceland
eOregon Medical Research Center, Portland, OR
fNovartis Pharmaceuticals, East Hanover, NJ
gNovartis Pharma AG, Basel, Switzerland
BACKGROUND: Interleukin (IL)-17A is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints. In phase 3 trials, secukinumab, a fully human anti–IL-17A monoclonal antibody, demonstrated robust efficacy in psoriasis, with rapid onset, high response rates, and durable response.
OBJECTIVE: To evaluate the efficacy of secukinumab in subjects with psoriasis and concomitant psoriatic arthritis (PsA) with respect to psoriasis symptoms and physical function, we conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials.
METHODS: The 52-week FIXTURE and ERASURE trials randomized subjects with moderate-to-severe plaque psoriasis to subcutaneous secukinumab 300 or 150 mg (Baseline, weeks 1, 2, 3, every 4 weeks from week 4 until week 48), etanercept 50 mg (twice weekly through week 12, once weekly thereafter through week 51; FIXTURE only), or placebo. In this analysis, changes in Health Assessment Questionnaire–Disability Index (HAQ-DI) and PASI 75 responses were assessed in subpopulations with concomitant PsA (n=196, FIXTURE; n=171, ERASURE).
RESULTS: Physical functioning (mean change from Baseline in HAQ-DI) was greater with secukinumab 300 mg vs. placebo at week 12 in both trials (FIXTURE, -0.41 vs. 0.02/P=0.0001; ERASURE, -0.35 vs. -0.08/P=0.0003); corresponding values were -0.29 for etanercept and -0.19 for secukinumab 150 mg in FIXTURE and -0.18 for secukinumab 150 mg in ERASURE. Greater responses were seen in subjects with greater Baseline disability (HAQ-DI ≥05). Week 12 PASI 75 responses were higher with secukinumab 300 mg/150 mg vs. placebo in FIXTURE (72%/59% vs. 2%) and ERASURE (68%/70% vs. 4%; all P<0.0001) and with secukinumab 300 mg vs. etanercept (72% vs 39%; P=0.0084).
CONCLUSION: Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant PsA.
ClinicalTrials.gov numbers: NCT01358578 (FIXTURE); NCT01365455 (ERASURE)
J Drugs Dermatol. 2015;14(8):821-833.
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Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy characterized by musculoskeletal signs and symptoms (arthritis, enthesitis, spondylitis) with associated joint pain and tenderness.1 It affects an estimated 0.3% to 1.0% of the general population,2 and is a common comorbidity in patients with psoriasis, in whom its prevalence is estimated at 30% (ranging from 18% to 42%, depending on geographic region). 3 For psoriasis patients the presence of PsA is associated with increased work-related problems, a substantial disability burden, and potentially reduced survival.4-7 The presence of PsA may also make the selection of treatment for psoriasis patients more challenging8 and many patients continue to experience significant symptoms and impairment of physical function despite available treatments.9
Interleukin (IL)-17A, the primary effector cytokine of the Th17 class of T-helper cells, has been implicated in the pathogenesis and chronic inflammation of psoriatic disease, with similar inflammatory cells affecting both skin and joints.10,11 Th17 levels are increased in the circulation of plaque psoriasis and PsA patients, in the skin of plaque psoriasis patients, and in the synovial fluid of PsA patients.12-15 Other potential cellular sources of IL-17A,