ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2626

Normalization of CRP Levels and Clinical Response to Ixekizumab in Patients with Psoriatic Arthritis: Results from the Spirit Studies

Bernard Combe1, Paul Emery2, Annelies Boonen3, Soyi Liu Leage4, Christophe Sapin4, Natalia Bello5 and Maxime Dougados6, 1CHU, Montpellier University, Montpelier, France, Montpellier, France, 2Leeds Musculoskeletal Biomedical Research Unit, LTHT Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK, Leeds, United Kingdom, 3Division of Rheumatology, Maastricht University, School for Public Health and Primary Care, Maastricht University Medical Centre, The Netherlands, Maastricht, Netherlands, 4Lilly France, Neuilly sur Seine Cedex, France, Neuilly sur Seine Cedex, France, 5Eli Lilly and Company (Spain), Alcobendas, Spain, Alcobendas, Spain, 6Rheumatology Department, Cochin Hospital, AP-HP, Paris Descartes University, Paris, France, Paris, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , ,

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: It is important to understand the association between early changes in inflammatory biomarkers and treatment response at later times after initiation of a biologic DMARD. In the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) phase 3, multicenter, double-blind studies of patients with active PsA, high-sensitivity CRP (hs-CRP) levels declined rapidly during the first 4 weeks (wks) of treatment with ixekizumab (IXE), a high affinity monoclonal antibody against IL-17A. This post-hoc analysis used data from the 2 studies to describe and compare efficacy outcomes at wk 24 according to change in hs-CRP levels from baseline (wk 0) to wk 4.

 

Methods: In SPIRIT-P1, biologic naïve patients received subcutaneous IXE 80 mg every 4 (Q4W; N=107) or 2 wks (Q2W; N=103) after a starting dose of 160 mg at wk 0, or adalimumab 40 mg every 2 wks (N=101), or placebo (PBO; N=106).1 In SPIRIT-P2, patients with an inadequate response/intolerance to TNF inhibitors received IXE Q4W (N=122) or Q2W (N=123), or PBO (N=118).2 For this analysis, the 2 IXE dose groups were combined and 3 patient hs-CRP subgroups were defined: normal (<6.0 mg/L) hs-CRP levels at wks 0 and 4; hs-CRP levels that normalized during treatment (elevated [≥6.0 mg/L] at wk 0, normal at wk 4); and elevated hs-CRP levels (normal/elevated at wk 0, elevated at wk 4). Between-treatment differences (combined IXE vs. PBO) across hs-CRP subgroups in efficacy outcomes were evaluated using the Cochran-Mantel-Haenszel general association test.

 

Results: Baseline patient characteristics, including BMI, was generally similar between the 3 hs-CRP subgroups, but with a numerically higher disease activity in those with elevated hs-CRP. Across the 3 subgroups, responses to active treatment were rapid and sustained at wk 24. In both studies, differences between IXE and PBO for clinical outcomes (ACR20/50/70, minimal disease activity, DAPSA low disease activity/remission) differed statistically significantly across hs-CRP subgroups as early as wk 4 or 8 (Tables 1 and 2). Numerically greater differences in the normalized hs-CRP subgroup was observed. Although performed on a smaller sample size, efficacy results across the 3 subgroups were generally consistent with those previously reported at wk 24 for the overall population in both studies.

 

Conclusion: In PsA, a response can be achieved after 24 wks of treatment with IXE regardless of prior biologic use, even when hs-CRP is still elevated at wk 4.

 

 References:

1.     Mease PJ et al. Ann Rheum Dis. 2017;76:79–87.

2.     Nash P et al. Lancet. 2017;389:2317–27.

 

 

 

Table 1. Response rates according to hs-CRP levels in patients with active PsA from the SPIRIT-P1 study. Results are expressed as proportions of patients in the ITT population calculated using NRI.

 

Response

Stable, normal hs-CRP

Normalized hs-CRP

Persistently elevated (increased) hs-CRP

 

PBO

(N=34)

IXE

(N=77)

PBO

(N=10)

IXE

(N=68)

PBO

(N=59)

IXE

(N=55)

ACR20

 

 

 

 

 

 

  Week 4***

17.7%

41.6%

10.0%

54.4%

18.6%

38.2%

  Week 8***

41.2%

58.4%

40.0%

60.3%

28.8%

61.8%

  Week 12***

41.2%

54.5%

40.0%

66.2%

25.4%

60.0%

  Week 24*

47.1%

58.4%

50.0%

86.8%

40.7%

65.5%

ACR50

 

 

 

 

 

 

  Week 4***

0.0%

18.2%

0.0%

27.9%

1.7%

18.2%

  Week 8***

14.7%

27.3%

10.0%

35.3%

6.8%

32.7%

  Week 12***

5.9%

37.7%

0.0%

41.2%

5.1%

30.9%

  Week 24**

17.6%

42.9%

30.0%

57.4%

18.6%

34.5%

ACR70

 

 

 

 

 

 

  Week 4ns

0.0%

2.6%

0.0%

10.3%

1.7%

1.8%

  Week 8*

5.9%

14.3%

10.0%

16.2%

0.0%

7.3%

  Week 12***

0.0%

14.3%

0.0%

23.5%

0.0%

9.1%

  Week 24**

5.9%

28.6%

0.0%

36.8%

10.2%

18.2%

MDAPASI

 

 

 

 

 

 

  Week 4**

2.9%

10.4%

10.0%

13.2%

1.7%

14.6%

  Week 8***

5.9%

26.0%

10.0%

26.5%

3.4%

18.2%

  Week 12***

11.8%

28.6%

10.0%

30.9%

0.0%

20.0%

  Week 24ns

20.6%

37.7%

50.0%

42.6%

11.9%

27.3%

DAPSA LDA

 

 

 

 

 

 

  Week 4*

12.1%

19.5%

10.0%

33.8%

6.8%

18.2%

  Week 8**

14.7%

37.7%

30.0%

29.4%

8.5%

23.6%

  Week 12*

26.5%

39.0%

30.0%

32.4%

8.5%

20.0%

  Week 24ns

23.5%

37.7%

40.0%

38.2%

22.0%

27.3%

DAPSA remission

 

 

 

 

 

 

  Week 4ns

0.0%

2.6%

0.0%

1.5%

0.0%

1.8%

  Week 8ns

2.9%

6.5%

10.0%

11.8%

0.0%

3.6%

  Week 12*

2.9%

11.7%

0.0%

13.2%

0.0%

3.6%

  Week 24*

8.8%

22.1%

20.0%

23.5%

1.7%

14.5%

nsnot significant, *p<0.05, **p<0.01, ***p<0.001 for differences between IXE and PBO across the 3 hs-CRP groups (Cochran-Mantel-Haenszel general association test).

 

Abbreviations: ACR20/50/70=20/50/70% improvement from baseline in ACR criteria; ACR=American College of Rheumatology; DAPSA=Disease Activity Index for PsA; hs-CRP=high sensitivity C-reactive protein; ITT=intent-to-treat; IXE=ixekizumab; LDA=low disease activity; MDAPASI=minimal disease activity according to the Psoriasis Area and Severity Index; NRI=non-responder imputation; PBO=placebo; PsA=psoriatic arthritis

 

 

 

Table 2. Response rates according to hs-CRP levels in patients with active PsA from the SPIRIT-P2 study. Results are expressed as proportions of patients in the ITT population calculated using NRI.

 

Response

 

 

Stable, normal hs-CRP

 

Normalized hs-CRP

 

Persistently elevated (increased) hs-CRP

 

PBO

(N=49)

IXE

(N=116)

PBO

(N=11)

IXE

(N=53)

PBO

(N=55)

IXE

(N=66)

ACR20

 

 

 

 

 

 

  Week 4***

22.4%

36.2%

27.3%

67.9%

9.1%

25.8%

  Week 8***

20.4%

42.2%

18.2%

62.3%

10.9%

34.8%

  Week 12***

32.7%

48.3%

18.2%

66.0%

14.5%

37.9%

  Week 24**

34.7%

50.0%

36.4%

75.5%

27.3%

43.9%

ACR50

 

 

 

 

 

 

  Week 4**

6.1%

17.2%

9.1%

22.6%

0.0%

4.5%

  Week 8***

2.0%

17.2%

0.0%

35.8%

0.0%

16.7%

  Week 12***

4.1%

32.8%

9.1%

39.6%

1.8%

25.8%

  Week 24***

12.2%

30.2%

9.1%

52.8%

10.9%

28.8%

ACR70

 

 

 

 

 

 

  Week 4ns

6.1%

4.3%

0.0%

11.3%

0.0%

0.0%

  Week 8**

2.0%

7.8%

0.0%

18.9%

0.0%

6.1%

  Week 12**

2.0%

11.2%

0.0%

17.0%

1.8%

12.1%

  Week 24***

0.0%

12.1%

9.1%

32.1%

1.8%

15.2%

MDAPASI

 

 

 

 

 

 

  Week 4ns

8.2%

11.2%

0.0%

11.3%

1.8%

7.6%

  Week 8***

8.2%

21.6%

0.0%

13.2%

1.8%

15.2%

  Week 12***

10.2%

23.3%

0.0%

24.5%

1.8%

18.2%

  Week 24***

10.2%

25.0%

0.0%

34.0%

1.8%

24.2%

DAPSA LDA

 

 

 

 

 

 

  Week 4ns

30.6%

21.6%

0.0%

20.8%

3.6%

13.6%

  Week 8**

22.4%

30.2%

0.0%

32.1%

7.3%

22.7%

  Week 12***

22.4%

38.8%

18.2%

34.0%

1.8%

28.8%

  Week 24**

22.4%

37.1%

27.3%

49.1%

16.4%

31.8%

DAPSA remission

 

 

 

 

 

 

  Week 4ns

6.1%

5.2%

0.0%

7.6%

0.0%

1.5%

  Week 8*

2.0%

7.8%

0.0%

7.5%

0.0%

3.0%

  Week 12**

2.0%

6.0%

0.0%

7.5%

0.0%

10.6%

  Week 24**

2.0%

11.2%

0.0%

13.2%

1.8%

10.6%

nsnot significant, *p<0.05, **p<0.01, ***p<0.001 for differences between IXE and PBO across the 3 hs-CRP groups (Cochran-Mantel-Haenszel general association test).

 

Abbreviations: ACR20/50/70=20/50/70% improvement from baseline in ACR criteria; ACR=American College of Rheumatology; DAPSA=Disease Activity Index for PsA; hs-CRP=high sensitivity C-reactive protein; ITT=intent-to-treat; IXE=ixekizumab; LDA=low disease activity; MDAPASI=minimal disease activity according to the Psoriasis Area and Severity Index; NRI=non-responder imputation; PBO=placebo; PsA=psoriatic arthritis

 

 

 

 

 

Disclosure: B. Combe, Pfizer, MSD, and Roche-Chugai; Consultant: Pfizer, UCB, Bristol-Myers Squibb, Janssen, Eli Lilly and Company, MSD, Roche-Chugai, AbbVie, Novartis, 2,Pfizer, Bristol-Myers Squibb, Eli Lilly and Company, MSD, 8; P. Emery, Consulting; Eli Lilly and Company, Abbvie, BMS, MSD, Novartis, Pfizer, Roche, Samsung, Sandoz, UCB, 5; A. Boonen, Lilly, Novartis, Sandoz, Janssen, 5,Lilly, Novartis, Sandoz, Janssen, 9,Abbvie, Celgene, 2; S. Liu Leage, Eli Lilly and Company, 1, 3; C. Sapin, Eli Lilly and Company, 1, 3; N. Bello, Eli Lilly and Company, 1, 3; M. Dougados, Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS , UCB, 2, 5.

To cite this abstract in AMA style:

Combe B, Emery P, Boonen A, Liu Leage S, Sapin C, Bello N, Dougados M. Normalization of CRP Levels and Clinical Response to Ixekizumab in Patients with Psoriatic Arthritis: Results from the Spirit Studies [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/normalization-of-crp-levels-and-clinical-response-to-ixekizumab-in-patients-with-psoriatic-arthritis-results-from-the-spirit-studies/. Accessed .

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