Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis: Long-Term (4-Year) Data from a Phase 3 Study

Iain B. McInnes¹, Alan J. Kivitz², Peter Nash³, Proton Rahman⁴, Juergen Rech⁵, Bruce Kirkham⁶, Sandra V. Navarra⁷, Kevin Ding⁸, Emma Ilsley⁹ and Luminita Pricop¹⁰, ¹University of Glasgow, Glasgow, United Kingdom, ²Altoona Center for Clinical Research, Duncansville, PA, ³University of Queensland, Brisbane, Australia, ⁴Memorial University, St John's, NF, Canada, ⁵University of Erlangen-Nuremberg, Erlangen, Germany, ⁶Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom, ⁷University of Santo Tomas Hospital, Manila, Philippines, ⁸Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁹Novartis Pharma AG, Basel, Switzerland, ¹⁰Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, East Hanover, NJ

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Biologics, interleukins (IL), monoclonal antibodies and psoriatic arthritis

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment

Session Type: ACR Poster Session C

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

Background/Purpose: Secukinumab (SEC), a fully human monoclonal IgG1 antibody that selectively neutralizes IL-17A, provided sustained improvement in the signs and symptoms of active psoriatic arthritis (PsA) over 2 years (yrs) in the FUTURE 2 study.¹ Herein, long-term (4-yr) efficacy and safety results in patients (pts) from FUTURE 2 study, including results of dose-escalation, are reported.

Methods: Overall, 397 pts with active PsA were randomized to either SEC (300, 150, or 75mg) or placebo weekly followed by every 4 weeks (wks) starting at Wk 8.¹ Of the overall randomized pts, approximately 1/3 had inadequate response [IR] to prior anti-TNF use. Pts were escalated from 150 to 300mg and from 75 to 150/300mg starting at Wk 128, if active signs of disease were observed based on physician’s judgement; the escalated dose was maintained thereafter. Assessments at Wk 208 included ACR20/50/70, PASI 75/90, HAQ-DI, SF-36 PCS, and resolution of dactylitis and enthesitis. Analyses by prior anti-TNF use (naïve/IR) and with/without concomitant methotrexate (MTX) were also assessed. ACR responses for dose-escalated pts included placebo-switchers. Data are reported as observed. Safety analysis included all pts who received ≥1 dose of SEC.

Results: Overall, 69/100 (69%), 70/100 (70%), and 62/99 (63%) pts originally randomized to SEC 300, 150, and 75mg, respectively, completed 208 wks of treatment. A total of 46/100 (46%) pts in the 150mg group were escalated to 300mg and 56/99 (57%) pts in the 75mg group escalated to 150/300mg. Clinical responses were sustained through Wk 208 with 300mg and sustained/further improved following dose-escalation to 300/150mg in the 150 and 75mg groups (Table). ACR20 response rates at Wk 208 in anti–TNF-naïve pts were 75.5%, 76.5%, and 71% in the 300, 150, and 75mg groups, respectively; corresponding rates in anti–TNF-IR pts were 60%, 71%, and 64%. ACR20 response rates in pts with concomitant MTX were 67.6%, 77.1%, and 78.8% in the 300, 150, and 75mg groups, respectively; corresponding rates in pts without concomitant MTX were 74.4%, 73%, and 58.6%. After dose-escalation, the proportion of pts with non/low level ACR responses improved, with corresponding increases in the proportion of pts achieving moderate/high ACR responses (Table). Over the study (SEC exposure of 238.6 pt-yrs), the type, incidence, and severity of adverse events were consistent with previous report.¹ Treatment-emergent anti-drug antibody was reported in 3 pts, with no neutralizing antibody or loss of efficacy. In the entire study, one death (due to sepsis) was reported in the 150mg group over 4 yrs.

Conclusion: SEC 300 and 150mg provided sustained improvement in the signs and symptoms of PsA over 4 yrs. Efficacy was sustained/further improved following dose-escalation. SEC was well tolerated, with no new/unexpected safety signals. Reference: 1. McInnes IB, et al. Rheumatology (Oxford) 2017;56:1993–2003.

Table
Efficacy Results at Wk 208
Endpoints, n/M (%), unless stated	Secukinumab 300mg (N = 100)		Secukinumab 150mg group (N = 100)*		Secukinumab 75mg group (N = 99)*
ACR20	52/73 (71.2)		54/72 (75.0)		43/ 62 (69.4)
ACR50	34/73 (46.6)		37/72 (51.4)		23/62 (37.1)
ACR70	26/73 (35.6)		18/72 (25.0)		8/62 (12.9)
^aPASI 75	25/31 (80.6)		35/43 (81.4)		24/36 (66.7)
^aPASI 90	18/31 (58.1)		30/43 (69.8)		15/36 (41.7)
HAQ-DI, mean change (SD)	n = 72 –0.59 (0.63)		n = 72 –0.51 (0.54)		n = 62 –0.33 (0.61)
SF-36 PCS, mean change (SD)	n = 73 6.9 (8.73)		n = 72 7.5 (7.35)		n = 62 5.3 (8.89)
^bResolution of enthesitis	29/41 (70.7)		33/46 (71.7)		29/45 (64.4)
^cResolution of dactylitis	29/34 (85.3)		22/25 (88.0)		24/26 (92.3)
ACR response rates before and after dose-escalation
ACR response, %	150mg to 300mg (M = 90)^d			75mg to 150mg (M = 45)^d
	Before dose-escalation^e	After dose-escalation		Before dose-escalation^e		After dose-escalation
ACR <20 (non-responder)	46.7	33.3		42.2		33.3
20≤ ACR <50	30.0	18.9		33.3		33.3
50≤ ACR <70	13.3	30.0		17.8		26.7
ACR ≥70	10.0	17.8		6.7		6.7
^*Secukinumab 150 and 75mg arms include 46 and 56 pts, respectively, who were escalated at Wk 128 ^aPASI responses assessed in pts with psoriasis affecting ≥3% body surface area at BL (300mg: N = 42; 150mg: N = 58, and 75mg: N = 50) ^bAssessed in pts (N = 56 [300mg], 64 [150mg], and 68 [75mg]) with this symptom at BL ^cAssessed in pts (N = 46 [300mg], 32 [150mg], and 33 [75mg]) with this symptom at BL ^dAll pts (including placebo-switchers) with non-missing assessment values at all time points are included ^eBefore dose-escalation is defined as the last assessment done on or before pt started on the higher dose BL, baseline; HAQ-DI, Health Assessment Questionnaire-Disability Index; PASI, Psoriasis Area and Severity Index; M, number of evaluable pts; N, total number of pts; n, number of responders; SF-36 PCS, Short Form 36 Physical Component Summary

Disclosure: I. B. McInnes, Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 2,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 5,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 8; A. J. Kivitz, Celgene, Janssen, Pfizer, Genentech, Novartis, and Sanofi, 5,Celgene, Pfizer, Sanofi-Regeneron, and Novartis, 8; P. Nash, Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 2,Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, 9; P. Rahman, Abbott, Abbvie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche, 5; J. Rech, BMS and Celgene, 2,Abbvie, BMS, Celgene, Fresenius, Medicap, MSD, Novartis, Pfizer, and Roche, 8; B. Kirkham, Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 2,Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 5,Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 8; S. V. Navarra, Pfizer, Novartis, AstraZeneca, Janssen, Astellas, Roche, 5, 8; K. Ding, Novartis, 1,Novartis, 3; E. Ilsley, Novartis, 1,Novartis, 3; L. Pricop, Novartis, 1, 3.

To cite this abstract in AMA style:

McInnes IB, Kivitz AJ, Nash P, Rahman P, Rech J, Kirkham B, Navarra SV, Ding K, Ilsley E, Pricop L. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis: Long-Term (4-Year) Data from a Phase 3 Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-psoriatic-arthritis-long-term-4-year-data-from-a-phase-3-study/. Accessed .

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