Secukinumab Improves Physical Function in Subjects With Plaque Psoriasis and Psoriatic Arthritis: Results from Two Randomized, Phase 3 Trials.
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).


CONCLUSIONS
Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant PsA. ClinicalTrials.gov numbers: NCT01358578 (FIXTURE); NCT01365455 (ERASURE)
Alice B
AB
Gottlieb
Richard G
RG
Langley
Sandra
S
Philipp
Bardur
B
Sigurgeirsson
Andrew
A
Blauvelt
Ruvie
R
Martin
Charis
C
Papavassilis
Shephard
S
Mpofu
D000203:Activities of Daily Living; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068800:Etanercept / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; D020381:Interleukin-17; C555450:secukinumab; D000068800:Etanercept