Subcutaneous Secukinumab Inhibits Radiographic Progression in Psoriatic Arthritis: Primary Results from a Large Randomized, Controlled, Double-Blind Phase 3 Study". American College of Rheumatology (ACR) Annual Meeting, San Diego CA, Nov. 2017.American College of Rheumatology (ACR) Annual Meeting (2017)
Background/Purpose: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has shown significant and rapid efficacy in psoriatic arthritis (PsA). We present primary results of FUTURE 5 (NCT02404350), the largest randomized controlled trial (RCT) of a biologic conducted to date in PsA, assessing efficacy of subcutaneous (sc) secukinumab 300 mg and 150 mg, including radiographic inhibition of structural damage, and safety.
Methods: Adults (n = 996) with active PsA, stratified by previous anti–TNF use, 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 received secukinumab 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 in tender 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, Wk 16 (non-responders), and Wk 24. Statistical analyses used non-responder imputation for binary variables, linear extrapolation for radiographic data, and missing at random assumption for continuous endpoints. Testing results used a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity.
Results: BL characteristics were balanced across arms. Approximately 30% of pts had experienced an inadequate response or intolerance to previous anti-TNF therapy. Secukinumab significantly improved ACR20 at Wk 16 vs. PBO. Radiographic progression (mTSS) was significantly 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 mg without LD), and 73% (PBO). All hierarchical endpoints were significant for secukinumab vs. PBO at Wk 16, except for enthesitis and dactylitis resolution for 150 mg without LD (Table).
Efficacy across all endpoints was greater in pts who were anti-TNF-naïve. The 300 mg and 150 mg groups had an earlier onset of response vs. pts who received 150 mg without LD. Adverse event (AE) rates at Wk 16 were 51.8% (300 mg), 52.7% (150 mg), 52.7% (150 mg without LD) and 58.7% (PBO); non-fatal serious AE rates were 2.3%, 3.2%, 1.4%, and 3.0%, respectively. No deaths were reported.
Conclusion: Subcutaneous secukinumab 300 mg with LD and 150 mg with and without LD, inhibited radiographic structural progression and provided rapid and clinically significant improvements in the signs, symptoms and physical function of pts with PsA. The safety profile was consistent with that previously reported with no new safety signals identified.
Publication DateOctober, 2017
Citation InformationPhilip Mease, Désirée van der Heijde, R Landewe, Shepard Mpofu, et al.. "Subcutaneous Secukinumab Inhibits Radiographic Progression in Psoriatic Arthritis: Primary Results from a Large Randomized, Controlled, Double-Blind Phase 3 Study". American College of Rheumatology (ACR) Annual Meeting, San Diego CA, Nov. 2017." American College of Rheumatology (ACR) Annual Meeting (2017)
Available at: http://works.bepress.com/philip-mease/149/