ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 17L

Subcutaneous Secukinumab Inhibits Radiographic Progression in Psoriatic Arthritis: Primary Results from a Large Randomized, Controlled, Double-Blind Phase 3 Study

Philip J Mease1, Désirée van der Heijde2, Robert B.M. Landewé3, Shephard Mpofu4, Proton Rahman5, Hasan Tahir6, Atul Singhal7, Elke Böttcher8, Sandra V. Navarra9, Karin Meiser4, Aimee Readie10, Luminita Pricop10 and Ken Abrams10, 1Swedish Medical Center and University of Washington, Seattle, WA, 2Leiden University Medical Center, Leiden, Netherlands, 3Academic Medical Center, Amsterdam and Atrium Medical Center, Heerlen, Netherlands, 4Novartis Pharma AG, Basel, Switzerland, 5Rheumatology, Memorial University of Newfoundland, St Johns, NF, Canada, 6Whipps Cross Hospital, London, United Kingdom, 7Southwest Rheumatology, Dallas, TX, 8Rheumazentrum Favoriten, Vienna, Austria, 9Rheumatology, University of Santo Tomas Hospital, Manila, Philippines, 10Novartis Pharmaceuticals Corporation, East Hanover, NJ

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: October 19, 2017

Keywords: , ,

Session Information

Date: Tuesday, November 7, 2017

Title: ACR Late-Breaking Abstract Poster

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

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).

Table. Summary of hierarchical primary endpoints

Week 16 Data‡

Secukinumab 300 mg sc

(n=222)

Secukinumab 150 mg sc

(n=220)

Secukinumab 150 mg sc without LD

(n=222)

Placebo

(n=332)

ACR20

(% responders)

62.6*

55.5*

59.5*

27.4

mTSS structural progression (mean change from BL to week 24)

0.08¥

0.17∞

–0.09¥

0.50

PASI 75/90

(% responders)

70.0*/53.6*

60.0*/36.8*

58.1*/31.6*

12.3/9.3

ACR50

(% responders)

39.6*

35.9*

32.0*

8.1

HAQ-DI score (LS mean change from BL)

–0.55*

–0.44*

–0.45*

–0.21

DAS28-CRP score (LS mean change from BL)

–1.49*

–1.29*

–1.29*

–0.63

Enthesitis resolution (%)

55.7†

54.6†

41.9

35.4

Dactylitis resolution (%)

65.9*

57.5†

56.3

32.3

*P < 0.0001; †P < 0.001; ¥ P < 0.01; ∞P < 0.05 un-adjusted p-values vs. placebo. ‡Week 24 data for mTSS. ACR, American College of Rheumatology response criteria; BL, baseline; DAS28-CRP, Disease Activity Score-28-joint count C-reactive protein; HAQ-DI, Health Assessment Questionnaire – Disability Index; LD, loading dosage; LS, least squares; mTSS, modified total van der Heijde Sharp score; PASI, Psoriasis Area and Severity Index; sc, subcutaneous

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.

Disclosure: P. J. Mease, AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, 5,AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Novartis, Pfizer, UCB, 8; D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCBAbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringe, 5,Director: Imaging Rheumatology bv, 9; R. B. M. Landewé, Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos, GlaxoSmithKline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB, and Wyeth, 5,Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, 2,Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, 8; S. Mpofu, Novartis, 1,Novartis, 3; P. Rahman, Janssen Pharmaceutica Product, L.P., 8,Amgen, AbbVie, BMS, Celgene, Pfizer, Janssen, Wyeth, EliLiiy, Novartis, 8,Amgen, AbbVie, BMS, Celgene, Pfizer, Janssen, Wyeth, EliLiiy, Novartis, 5; H. Tahir, Abbvie, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,UCB, 5,Eli-Lily, 5,Janssen Pharmaceutica Product, L.P., 5,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2; A. Singhal, Abbvie, 2,Gilead, 2,Sanofi, 2,Regeneron, 2,Amgen, 2,Roche Pharmaceuticals, 2,BMS, 2,Janssen Pharmaceutica Product, L.P., 2,Lilly, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,UCB, 2,AstraZeneca, 2,MedImmune, 2,FujiFilm, 2,Nichi-Iko, 2,Mallinckrodt, 2,Abbvie, 8; E. Böttcher, Amgen, 5,Roche Pharmaceuticals, 5,Eli-Lily, 5,Pfizer Inc, 5,MSD, 5,Novartis Pharmaceutical Corporation, 5,Amgen, 8,Roche Pharmaceuticals, 8,Eli-Lily, 8,Pfizer Inc, 8,MSD, 8,Novartis Pharmaceutical Corporation, 8; S. V. Navarra, Pfizer Inc, 5,Novartis Pharmaceutical Corporation, 5,AstraZeneca, 5,Janssen Pharmaceutica Product, L.P., 5,Astellas, 5,Roche Pharmaceuticals, 5,Pfizer Inc, 8,Novartis Pharmaceutical Corporation, 8,AstraZeneca, 8,Janssen Pharmaceutica Product, L.P., 8,Astellas, 8,Roche Pharmaceuticals, 8; K. Meiser, Novartis, 3; A. Readie, Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1; L. Pricop, Novartis Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; K. Abrams, Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1.

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). https://acrabstracts.org/abstract/subcutaneous-secukinumab-inhibits-radiographic-progression-in-psoriatic-arthritis-primary-results-from-a-large-randomized-controlled-double-blind-phase-3-study/. Accessed .

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/subcutaneous-secukinumab-inhibits-radiographic-progression-in-psoriatic-arthritis-primary-results-from-a-large-randomized-controlled-double-blind-phase-3-study/