ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: L11

Etanercept and Methotrexate As Monotherapy or in Combination in Patients with Psoriatic Arthritis: A Phase 3, Double-Blind, Randomized Controlled Study

Philip J. Mease1, Dafna D. Gladman2, David H. Collier3, Christopher T. Ritchlin4, Philip S. Helliwell5, Lyrica Liu6, Gregory J. Kricorian3 and James B. Chung3, 1Swedish Medical Center and University of Washington, Seattle, WA, 2University of Toronto, Toronto, ON, Canada, 3Amgen Inc., Thousand Oaks, CA, 4University of Rochester Medical Center, Rochester, NY, 5University of Leeds, Leeds, United Kingdom, 6Amgen Inc., South San Francisco, CA

Meeting: 2018 ACR/ARHP Annual Meeting

Date of first publication: October 4, 2018

Keywords: , , , ,

Session Information

Date: Tuesday, October 23, 2018

Title: Late-Breaking Abstract Poster Session

Session Type: ACR Late-breaking Abstract Session

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

Background/Purpose:  Methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) such as etanercept (ETN) are often prescribed for psoriatic arthritis (PsA) either alone or in combination, but fundamental gaps in knowledge about their optimal use remain.  This study examined the efficacy of MTX monotherapy relative to ETN monotherapy and the value of adding MTX to ETN in key clinical domains of PsA, including progressive joint damage.

Methods:  This phase 3, randomized controlled, double-blind international study enrolled patients with active PsA based on Classification Criteria for Psoriatic Arthritis (CASPAR).  They were naïve to biologic drugs with no prior MTX for PsA.  A total of 851 patients were randomized to 3 groups for 48 weeks: ETN 50 mg plus MTX 20 mg weekly (Combo; N = 283); ETN 50 mg plus oral placebo weekly (ETN-mono; N = 284); or MTX 20 mg plus injectable placebo weekly (MTX-mono; N = 284).  The primary endpoint was the American College of Rheumatology (ACR)20 response at week 24.  The key secondary endpoint was Minimal Disease Activity (MDA) response at week 24.  The study was powered to detect a treatment difference in ACR20 and MDA at week 24 between the Combo and the MTX-mono arms and between the ETN-mono and MTX-mono arms, tested in a Bonferroni-based gatekeeping chain procedure.  Additional endpoints included other measures of inflammatory arthritis, radiographic progression, severity of non-articular disease manifestations, and patient-reported outcomes.

Results:  Baseline characteristics were well balanced in the 3 study arms.  Mean (SD) age was 48.4 (13.1) years, most patients were white, and median PsA duration was 0.6 years (mean [SD] 3.2 [6.3] years).  From weeks 4 to 24, the MTX-containing arms maintained a mean MTX dose >18.8 mg.  ACR20 and MDA response rates at week 24 were significantly greater for ETN-mono vs MTX-mono (ACR20: 60.9% vs 50.7% [P=0.029]; MDA: 35.9% vs 22.9% [P=0.005]) and for Combo vs MTX-mono (ACR20: 65.0% vs 50.7% [P=0.005]; MDA: 35.7% vs 22.9% [P= 0.005]).  At week 48, the Combo and ETN-mono arms showed less radiographic progression compared with the MTX-mono arm (Table).  Other secondary outcomes are shown in the Table.  Overall, the Combo and ETN-mono arms had similar results, with some differences in skin outcomes.  Aside from GI events, adverse event rates were similar in the 3 study arms.  No new safety signals were seen. 

Conclusion:   This is the first head-to-head comparison of MTX and a TNFi to address fundamental questions in the treatment of PsA.  ETN monotherapy or ETN in combination with MTX showed greater efficacy compared with MTX monotherapy.  Addition of MTX to ETN did not appear to improve efficacy compared with ETN alone.  These results support the use of ETN as monotherapy for PsA.

Acknowledgment:  Linda Rice at Amgen Inc. and Julia Gage (on behalf of Amgen Inc.) assisted in abstract drafting. The study sponsor was Amgen Inc.

Table. Primary outcome and other measures of disease activity at week 24a

 

MTX Monotherapy
N = 284

ETN Monotherapyb
N = 284

Combination b
N = 283

ACR 20 response, %

50.7

60.9; P=0.029

65.0; P=0.005

ACR 50 response, %

30.6

44.4; P=0.006

45.7; P<0.001

ACR 70 response, %

13.8

29.2; P<0.001

27.7; P<0.001

MDA response, %

22.9

35.9; P=0.005

35.7; P=0.005

VLDA response, %

4.8

15.2; P<0.001

14.3; P<0.001

PASDAS

 

 

 

   Mean (SE) at BL

   Change from BL, mean (SE)

6.1 (0.1)

-2.0 (0.1)

6.0 (0.1)

-2.6 (0.1); P<0.001

6.0 (0.1)

-2.6 (0.1); P<0.001

DAPSA

 

 

 

   Mean (SE) at BL

   Change from BL, mean (SE)

46.5 (1.4)

-22.6 (1.4)

43.4 (1.4)

-25.0 (1.3); P=0.24

43.8 (1.4)

-24.9 (1.4); P=0.23

LDI

 

 

 

   > 0 at BL, %

   Change from BL, mean (SE)

   Patients with resolution, %

34.5

-128.8 (26.8)

65.2

33.8

-119.1 (20.7); P=0.85

76.4; P=0.12

31.8

-110.2 (22.7); P=0.68

79.3; P=0.057

SPARCC Enthesitis

 

 

 

   > 0 at BL, %

   Change from BL, mean (SE)

   Patients with resolution, %

67.3

-3.1 (0.3)

43.1

66.5

-3.0 (0.3); P=0.93

52.6; P=0.11

69.3

-2.9 (0.3); P=0.70

47.5; P=0.55

BSA

 

 

 

   % improvement from BL in patients with ≥ 3% BSA at BL, mean (SE) [n]c

   % improvement from BL in patients with ≥ 10% BSA at BL, mean (SE) [n]c

66.1 (2.8) [179]

65.7 (3.7) [92]

69.8 (2.7) [166]; P=0.49

74.2 (3.3) [91]; P=0.12

75.5 (3.7) [163]; P=0.031

81.6 (2.6) [86]; P<0.001

sPGAd

 

 

 

   Clear or almost clear (0/1) status for patients with ≥ 3% BSA at BL, %

   Clear or almost clear (0/1) status for patients with ≥ 10% BSA at BL, %

66.3

59.3

72.3; P=0.40

79.1; P=0.012

77.6; P=0.019

78.8; P=0.004

mNAPSI

 

 

 

   > 0 at BL, %

   Change from BL, mean (SE)

   Patients achieving a score of 1, %

65.1

-1.1 (0.2)

38.8

72.5

-1.5 (0.2); P=0.10

43.5; P=0.44

69.6

-1.7 (0.2); P=0.020

48.8; P=0.14

HAQ-DI

 

 

 

   Mean at BL (SE)

   Change from BL, mean (SE)

1.27 (0.04)

-0.41 (0.04)

1.15 (0.04)

-0.44 (0.04); P=0.67

1.15 (0.04)

-0.47 (0.04); P=0.34

SF-36

 

 

 

   Overall mean (SE) at BL

   Total change from BL, mean (SE)

   PCS change from BL, mean (SE)

   MCS change from BL, mean (SE)

80.8 (0.9)

9.2 (0.8)

6.0 (0.6)

3.3 (0.6)

82.9 (0.9)

10.6 (0.8); P=0.31

7.8 (0.6); P=0.033

2.8 (0.6); P=0.56

83.6 (0.9)

11.3 (0.9); P=0.11

8.0 (0.6); P=0.015

3.3 (0.6); P=0.97

Radiographic Progression

 

 

 

   Erosion score of > 0 at baseline, %

   mTSS change from BL at week 48, mean (SE)

   Non-progression at week 48 (mTSS change ≤ 0 from baseline), %

82.9

0.08 (0.03)

89.4

80.6

-0.04 (0.04); P=0.014

94.7; P=0.088

81.8

-0.01 (0.03); P=0.041

94.7; P=0.033

American College of Rheumatology; BL, baseline; BSA, (psoriasis-affected) body surface area; DAPSA, Disease Activity Index For Psoriatic Arthritis; ETN, etanercept; HAQ-DI, Health Assessment Questionnaire Disability Index; LDI, Leeds Dactylitis Index; MCS, mental component summary; MDA, minimal disease activity; mNAPSI, modified Nail Psoriasis Severity Index; mTSS, van der Heijde modified Total Sharp Score (scoring system for X-rays of the hands and feet taken at baseline and at weeks 24 and 48); MTX, methotrexate; PASDAS, Psoriatic Arthritis Disease Activity Score; PCS, physical component summary; SE, standard error; SF-36, Short Form (36) health survey; SPARCC, Spondyloarthritis Research Consortium of Canada; sPGA, static Physician Global Assessment; VLDA, Very Low Disease Activity. aExcept for the radiographic progression endpoints, which are shown for week 48. bP-values are for the comparison with MTX monotherapy.  Only the P-values in bold for the ACR 20 primary endpoint and MDA key secondary endpoint measured statistical significance.  All other P-values are descriptive and are italicized. c[n] refers to the number of patents analyzed. dThe sPGA scale ranges from 0 (clear) to 5 (severe).

 

Disclosure: P. J. Mease, AbbVie Inc., 2, 5, 8,Amgen Inc., 2, 5, 8,Bristol-Myers Squibb, 2, 5, 8,Celgene Corporation, 2, 5, 8,Galapagos, 5,Genentech, Inc., 8,Janssen, 2, 5, 8,Eli Lilly and Co., 2, 5,Novartis, 2, 5, 8,Pfizer, Inc., 2, 5, 8,Sun, 2, 5,UCB, Inc., 2, 5, 8; D. D. Gladman, AbbVie Inc., 2, 5,Bristol-Myers Squibb, 5, 9,Celgene Corporation, 2, 5, 9,Eli Lilly and Co., 2, 5, 9,Janssen, 2, 5,Novartis, 2, 5, 9,Pfizer, Inc., 2, 5, 9,UCB, Inc., 2, 5, 9,Amgen Inc., 2, 5, 9; D. H. Collier, Amgen Inc., 3,Amgen Inc., 1; C. T. Ritchlin, Amgen Inc., 2, 5,AbbVie Inc., 2, 5,UCB, Inc., 2, 5,Novartis, 5,Pfizer, Inc., 5,Janssen, 5; P. S. Helliwell, AbbVie Inc., 2, 8, 9,Amgen Inc., 2, 8,Janssen, 8, 9,Pfizer, Inc., 2, 9,UCB, Inc., 9,Galapagos, 5; L. Liu, Amgen Inc., 1,Amgen Inc., 3; G. J. Kricorian, Amgen Inc., 1,Amgen Inc., 3; J. B. Chung, Amgen Inc., 1, 3.

To cite this abstract in AMA style:

Mease PJ, Gladman DD, Collier DH, Ritchlin CT, Helliwell PS, Liu L, Kricorian GJ, Chung JB. Etanercept and Methotrexate As Monotherapy or in Combination in Patients with Psoriatic Arthritis: A Phase 3, Double-Blind, Randomized Controlled Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/etanercept-and-methotrexate-as-monotherapy-or-in-combination-in-patients-with-psoriatic-arthritis-a-phase-3-double-blind-randomized-controlled-study/. Accessed .

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