Secukinumab Provides Early and Sustained Improvements in Health-Related Quality of Life in Patients with Psoriatic Arthritis: Pooled Results from the Secukinumab Phase 3 Trial Program

Vibeke Strand¹, Oliver FitzGerald², Laura C. Coates³, Jessica Walsh⁴, Juan D. Cañete⁵, Peter Nash⁶, Eric Davenport⁷, Luminita Pricop⁸, Gregory Hustache⁹, Nicolas Scheuer⁹, Isabelle Gilloteau⁹ and Matthias Augustin¹⁰, ¹Stanford University, Palo Alto, CA, USA, Palo Alto, CA, ²St Vincent's University Hospital and Conway Institute, University College Dublin, Ireland, Dublin, Ireland, ³University of Oxford, Oxford, UK, Oxford, United Kingdom, ⁴University of Utah School of Medicine, Salt Lake City, UT, USA, Salt Lake City, UT, ⁵Rheumatology Deparment, Hospital Clinic and IDIBAPS, Barcelona, Spain, Barcelona, Spain, ⁶University of Queensland, Brisbane, Queensland, Australia, St Lucia, Brisbane, Australia, ⁷RTI Health Solutions, Research Triangle Park, NC, USA, Research Triangle Park, NC, ⁸Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, East Hanover, NJ, ⁹Novartis Pharma AG, Basel, Switzerland, Basel, Switzerland, ¹⁰University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: 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:

Improving health-related quality of life (HRQoL) is a key goal of psoriatic arthritis (PsA) therapy. Secukinumab, a fully-human IL-17A inhibitor, has been shown to rapidly and sustainably improve multiple clinical domains of PsA. This comprehensive pooled analysis assessed the impact of secukinumab on HRQoL, assessed by the Short Form-36 Health Survey (SF-36), in TNF inhibitor (TNF)-naïve and TNF inhibitor inadequate responder/intolerant (TNF-IR) patients (pts) with PsA in FUTURE 2, 3, 4 and 5 (NCT01752634; NCT01989468; NCT02294227; NCT02404350). <>Methods:

Pts with active PsA, stratified by TNF status, were randomized to subcutaneous placebo (PBO) or secukinumab 75 mg (FUTURE 2), 150 mg (FUTURE 2, 3, 4, 5), 150 mg no load (FUTURE 4, 5) or 300 mg (FUTURE 2, 3, 5) administered at baseline (BL) and Wks 1, 2, 3 and 4, followed by every 4 wks (or every 4 wks from BL in no load arms). At Wk 16 or 24, pts on PBO were re-randomized to secukinumab. Mixed-model for repeated measures was used to assess change in SF-36 from BL to Wk 16; observed data are presented at Wk 52. The proportion of pts reporting improvements meeting or exceeding the minimal clinically important differences for SF-36 physical (PCS responders), mental component summary (MCS responders) and individual SF-36 domains was assessed. Non-responder imputation was used, and the proportion of SF-36 responders was compared using Fisher’s exact test. Pooled data for pts receiving licensed doses of secukinumab (300 or 150 mg) or PBO are shown. <>Results:

Of 2049 pts overall, 461, 572, 335 and 681 were in the secukinumab 300 mg, 150 mg, 150 mg (no load) and PBO groups, respectively, of whom approx. 30% were TNF-IR. Least squares mean changes from BL in PCS and MCS at Wk 16 were significantly improved vs PBO for all secukinumab doses, overall and in both TNF-naïve and TNF-IR pts (Table 1). All individual domain scores were also significantly improved with secukinumab vs PBO, except role-emotional in TNF-IR pts with secukinumab 150 mg. There was a significantly higher proportion of SF-36 responders (PCS, MCS and individual domains) in the secukinumab groups at Wk 16 vs PBO in the overall sample (Table 2), except for role-emotional with secukinumab 150 mg. There were consistent trends for higher SF-36 response rates with secukinumab vs PBO regardless of TNF status, with higher SF-36 response rates in TNF-naïve pts. Improvements in PCS, MCS, individual domain scores and response rates were sustained to Wk 52. <>Conclusion:

Secukinumab 300 mg and 150 mg offered significant and sustained improvements in HRQoL (SF-36) up to 52 wks in pts with PsA, regardless of TNF status.

Table 1. Least squares mean changes from baseline to Week 16 in SF-36 scores in TNF-naïve and TNF-IR patients in a pooled analysis of FUTURE 2, FUTURE 3, FUTURE 4, and FUTURE 5 RCTs.

LS mean change from baseline

Secukinumab
300 mg

Secukinumab
150 mg

Secukinumab
150 mg (no load)

Placebo

(N = 461)

(N = 572)

(N = 335)

(N = 681)

Overall group

TNF-naïve

TNF-IR

Overall group

TNF-naïve

TNF-IR

Overall group

TNF-naïve

TNF-IR

Overall group

TNF-naïve

TNF-IR

PCS

6.74*

7.32*

6.49*

5.10*

5.78*

4.65*

4.88*

5.50*

4.48**

1.58

2.14

1.24

MCS

3.68*

3.97*

3.55**

3.31*

3.80*

2.73***

3.30**

3.60**

3.09***

1.02

1.46

0.45

Physical functioning

17.58*

19.31*

16.70*

12.68*

14.75*

11.01*

13.15*

14.98*

11.78**

3.64

5.97

0.80

Role-physical

16.93*

17.97*

17.68*

13.33*

15.60*

11.10***

12.66*

14.61*

10.81

5.42

6.49

5.88

Bodily pain

18.50*

20.13*

17.93*

15.29*

16.84*

14.89*

16.80*

13.13**

5.05

6.46

4.69

General health

10.09*

11.58*

8.80*

7.02*

8.53*

5.46**

6.20*

6.73*

7.11**

1.04

2.33

–0.07

Vitality

13.06*

14.36*

12.43*

10.61*

12.35*

8.93**

10.33*

11.18*

10.82**

2.90

3.95

2.97

Social functioning

13.42*

14.01*

14.40*

12.27*

13.55*

11.74**

11.28*

12.65*

10.35**

3.30

4.78

1.94

Role-emotional

10.33*

10.84*

11.14**

7.43**

9.14**

5.55

8.57**

9.86**

7.38

3.50

4.60

2.74

Mental health

8.15*

9.33*

6.69**

7.21*

8.20*

6.29**

6.98*

7.79**

6.31**

1.82

3.14

–0.11

* p < 0.0001; ** p < 0.01, *** p < 0.05 versus placebo.

LS = least squares; MCS = mental component summary; MMRM = Mixed model for repeated measures; PCS = physical component summary; RCT, randomized controlled trial; TNF-IR, tumor necrosis factor inhibitor inadequate responder/intolerant; TNF-naïve, tumor necrosis factor inhibitor naïve.

MMRM was used to assess change in SF-36 from baseline to Week 16.

Table 2. Proportion of SF-36 responders (improvements ≥MCID) at Weeks 16 and 52 in a pooled analysis of FUTURE 2, FUTURE 3, FUTURE 4, and FUTURE 5 RCTs.
SF-36 Responder rates (%)	Secukinumab 300 mg			Secukinumab 150 mg		Secukinumab 150 mg (no load)		Placebo
	(N = 461)			(N = 572)		(N = 335)		(N = 681)
	Week 16	Week 52	Week 16		Week 52	Week 16	Week 52	Week 16
PCS	65.9*	65.7	59.4*		55.1	61.8*	52.2	42.0
MCS	48.4**	49.4	50.0**		44.9	49.9**	45.1	40.4
Physical functioning	70.9*	66.1	65.2*		59.1	65.1**	54.0	50.2
Role-physical	65.5*	62.8	63.8*		56.0	63.0**	52.2	48.5
Bodily pain	66.8*	68.2	65.2*		59.1	64.2*	61.1	45.4
General health	62.0*	60.3	57.9*		49.4	53.7**	50.4	42.9
Vitality	63.8*	59.0	63.1*		54.8	62.4*	62.8	44.1
Social functioning	56.2*	52.3	55.9*		49.7	54.3*	45.1	39.4
Role-emotional	51.0**	50.6	48.3		43.8	45.4	37.2	40.7
Mental health	58.8**	57.7	59.8*		50.3	55.8**	61.1	45.1
* p < 0.0001; p < 0.01, * p < 0.05 versus placebo. MCID = minimal clinically important difference; MCS = mental component summary; PCS = physical component summary; RCT = randomized controlled trial. PCS and MCS response: patients with ≥2.5 point increase in component summary score. SF-36 Individual domain response: patients with ≥5.0 point increase in SF-36 individual domain score.

Disclosure: V. Strand, AbbVie, Amgen, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB, 5; O. FitzGerald, Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCB, 2, 9; L. C. Coates, Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCB, 2, 9; J. Walsh, Novartis, 5; J. D. Cañete, AbbVie, Boehringer, 9; P. Nash, AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, 2,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, 5,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Hospira, MSD, Pfizer, Janssen, UCB, Novartis, Roche, 8; E. Davenport, RTI Health Solutions, which received funding for this work from Novartis, 3; L. Pricop, Novartis, 1, 3; G. Hustache, Novartis, 1, 3; N. Scheuer, Novartis, 1, 3; I. Gilloteau, Novartis, 1, 3; M. Augustin, AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Hexal, Janssen, Leo, Lilly, Medac, Mundipharma, MSD, Novartis, Pfizer, Sandoz, UCB, and Xenoport, 9.

To cite this abstract in AMA style:

Strand V, FitzGerald O, Coates LC, Walsh J, Cañete JD, Nash P, Davenport E, Pricop L, Hustache G, Scheuer N, Gilloteau I, Augustin M. Secukinumab Provides Early and Sustained Improvements in Health-Related Quality of Life in Patients with Psoriatic Arthritis: Pooled Results from the Secukinumab Phase 3 Trial Program [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/secukinumab-provides-early-and-sustained-improvements-in-health-related-quality-of-life-in-patients-with-psoriatic-arthritis-pooled-results-from-the-secukinumab-phase-3-trial-program/. Accessed .

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