Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose: Secukinumab, a fullyhuman monoclonal antibody that selectivelyneutralizes IL-17A, has shownsignificant and rapid efficacy in psoriatic arthritis (PsA). We present primaryresults of FUTURE 5 (NCT02404350),the largest randomized controlled trial (RCT) of a biologic conducted to date inPsA, assessing efficacy of subcutaneous (sc) secukinumab 300 mg and 150 mg, includingradiographic inhibition of structural damage, and safety.
Methods: Adults (n =996) with active PsA, stratified by previous anti–TNFuse, were randomized 2:2:2:3 to sc secukinumab 300 mg with loading dosage (LD),150 mg with LD, 150 mg without LD, or placebo (PBO). All groups receivedsecukinumab or PBO at baseline (BL), Wks 1, 2, 3, and 4, and then every 4 wks. At Wk 16, PBO non-responders (patients [pts] with <20% improvement from BL intender or swollen joint counts) were switched to secukinumab 300 mg or 150 mg;remaining PBO pts were switched at Wk 24. The primary endpoint was ACR20 at Wk 16. The key secondary endpoint was radiographic structural progression,as measured by modified total van der Heijde Sharp score (mTSS), assessed by two blinded readers, based on hand/wrist/foot X-rays obtained at BL, Wk16 (non-responders), and Wk 24. Statistical analyses used non-responderimputation for binary variables, linear extrapolation for radiographic data,and missing at random assumption for continuous endpoints. Testing results useda pre-defined hierarchical hypothesis testing strategy to adjust formultiplicity.
Results: BL characteristics werebalanced across arms. Approximately30% of pts had experienced an inadequate response or intolerance to previousanti-TNF therapy. Secukinumabsignificantly improved ACR20 at Wk 16 vs. PBO. Radiographic progression (mTSS) wassignificantly inhibited at Wk 24 in all secukinumab arms vs. PBO (Table).A greater proportion of pts had no radiographic progression (change from BL in mTSS≤0.5) with secukinumab vs. PBO: 88% (300 mg), 79% (150 mg), 83% (150 mgwithout LD), and 73% (PBO). All hierarchical endpoints were significant forsecukinumab vs. PBO at Wk 16, except for enthesitis and dactylitis resolutionfor 150 mg without LD (Table).
Efficacyacross all endpoints was greater in pts who were anti-TNF-naïve. The 300 mg and150 mg groups had an earlier onset of response vs. pts who received 150 mg withoutLD. Adverse event (AE) ratesat Wk 16 were 51.8% (300 mg), 52.7% (150 mg), 52.7% (150 mg without LD) and58.7% (PBO); non-fatal serious AE rates were 2.3%, 3.2%, 1.4%, and 3.0%,respectively. No deaths were reported.
Conclusion: Subcutaneous secukinumab300 mg with LD and 150 mg with and without LD, inhibited radiographic structuralprogression and provided rapid and clinically significant improvements in thesigns, symptoms and physical function of pts with PsA. The safety profile wasconsistent with that previously reported with no new safety signals identified.
To cite this abstract in AMA style:Mease PJ, van der Heijde D, Landewé RBM, Mpofu S, Rahman P, Tahir H, Singhal A, Böttcher E, Navarra SV, Meiser K, Readie A, Pricop L, Abrams K. Subcutaneous Secukinumab Inhibits Radiographic Progression in Psoriatic Arthritis: Primary Results from a Large Randomized, Controlled, Double-Blind Phase 3 Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/subcutaneous-secukinumab-inhibits-radiographic-progression-in-psoriatic-arthritis-primary-results-from-a-large-randomized-controlled-double-blind-phase-3-study/. Accessed November 18, 2017.
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