ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2L

Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study

Peter C. Taylor1, Edward C. Keystone2,3, D. van der Heijde4, Yoshiya Tanaka5, Taeko Ishii6, Kahaku Emoto6, Lili Yang6, Vipin Arora6, Carol L. Gaich6, Terence Rooney6, Douglas E. Schlichting6, William Macias6, Stephanie de Bono6 and Michael E. Weinblatt7, 1Nuffield Dept. of Orthopaedics, Rheumatology and Musculoskeletal, Sciences, Kennedy Institute of Rheumatology, University of Oxford,, Oxford, United Kingdom, 2University of Toronto, Toronto, ON, Canada, 3Rebecca MacDonald Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 4Leiden University Medical Center, Leiden, Netherlands, 5The First Dept. of Internal Medicine, University of Occupational & Environmental Health, Kitakyusyu, Japan, 6Eli Lilly and Company, Indianapolis, IN, 7Brigham and Women’s Hospital, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: October 27, 2015

Keywords: , , ,

Session Information

Date: Tuesday, November 10, 2015

Title: ACR Late-breaking Abstract Session

Session Type: ACR Late-breaking Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: In phase 3 studies, baricitinib (bari) improved disease activity in patients (pts) with active RA and an inadequate response (IR) to conventional synthetic DMARDs1 or biologic DMARDs2. This abstract reports the 24-wk results from a 52-wk, global, phase 3, double-blind, placebo (PBO) and active-controlled study of bari in MTX-IR RA pts.

Methods: Pts with active RA (TJC≥6 & SJC≥6 & hsCRP≥6 mg/L) despite stable background MTX were randomized 3:3:2 to PBO, bari 4 mg once daily (QD), or adalimumab (ADA) 40 mg biweekly (Q2W), stratified by region and baseline joint erosion status. Non-responders were rescued from Wk 16. At Wk 24, pts on PBO switched to bari 4 mg QD. The primary endpoint was ACR20 response at Wk 12 for bari vs. PBO. Major secondary endpoints included comparisons of bari vs. ADA for ACR20 and change in DAS28-CRP at Wk 12.

Results: Of 1305 randomized pts, 89%, 94% and 93% completed Wk 24 in PBO, bari and ADA groups, respectively. Rescue rates were 26%, 7% and 12% for PBO, bari and ADA, respectively. ACR20 response at Wk 12 was higher for bari vs. PBO (70% vs. 40%, p≤.001 – Table 1). At Wks 12 and 24, statistically significant improvements in ACR 20/50/70 & HAQ-DI response rates, and DAS28, CDAI, and SDAI low disease activity and remission rates were seen for bari vs. PBO, many as early as Wk 1. Compared to ADA, bari was superior with respect to measures including ACR20 response and improvement in DAS28-CRP at Wk 12. Compared to PBO, daily diary measures of morning joint stiffness (MJS) duration and severity, worst tiredness, and worst joint pain were significantly improved in pts receiving bari, from as early as Wk 1. Rates of treatment-emergent adverse events (TEAEs), including infections, were higher for bari and ADA compared to PBO (Table 2). Compared to PBO, serious adverse events (SAE) rates were similar for bari and lower for ADA; serious infection rates were similar across groups. Two deaths occurred (bari), 1 pneumonia and 1 duodenal ulcer haemorrhage. Five malignancies were reported, 2 bari and 3 PBO. Three potential opportunistic infections occurred, 2 bari and 1 PBO; none were SAEs. One case of tuberculosis occurred (ADA). There were no GI perforations. Lab abnormalities were consistent with other phase 3 studies1,2; few led to discontinuation.

Conclusion: In pts with active RA despite background MTX, once-daily oral bari was associated with significant clinical improvements compared to PBO and to ADA, with an acceptable safety and tolerability profile.

References: 1Dougados M et al. Ann Rheum Dis 2015;74(S2):79; 2Genovese M et al. Ann Rheum Dis 2015;74(S2):75-76.

 

Wk 12

Wk 24

Table 1: Efficacy Measures

PBO

(N=488)

Bari

(N=487)

ADA

(N=330)

PBO

(N=488)

Bari

(N=487)

ADA

(N=330)

ACR20

40

70*** +

61***

37

74*** +

66***

ACR50

17

45*** ++

35***

19

50***

46***

ACR70

5

19*** +

13***

8

30*** +

22***

DAS28-CRP ≤3.2

14

44*** ++

35***

19

52***

48***

DAS28-CRP <2.6

4

24***

19***

8

35***

32***

DAS28-ESR ≤3.2

7

24***

21***

10

32***

34***

DAS28-ESR <2.6

2

11***

12***

5

18***

18***

CDAI ≤10

17

40*** +

33***

20

50***

48***

CDAI ≤2.8

2

8***

7**

4

16***

12***

SDAI ≤11

16

42*** +

35***

20

51***

49***

SDAI ≤3.3

2

8***

8***

3

16***

14***

HAQ-DI MCID ≥0.22

58

75***

71***

45

73*** +

64***

LS mean D DAS28-CRP#

-1.0

-2.2*** +++

-1.9***

-1.1

-2.4*** +

-2.2***

Duration of MJS, median (minutes)

60

27*** +

37***

Not applicable

Severity of MJS, LS mean‡

4.1

3.0*** ++

3.5***

Worst tiredness, LS mean‡

4.3

3.6*** +

3.9***

Worst joint pain, LS mean‡

4.6

3.4*** +++

4.0***

Patients received stable background MTX throughout the study. Data are % pts (NRI), unless otherwise stated; #Data are least squares (LS) mean change from baseline; Data for duration and severity of MJS, worst tiredness, and worst joint pain were collected in a daily diary until week 12; ‡Pts recorded these measures using a numeric rating scale (0-10), higher score indicates worse state; *p≤.05, **p≤.01, ***p≤.001 vs. PBO; +p≤.05, ++p≤.01, +++p≤.001 vs. ADA

 

Wks 0-12

Wks 0-24

Table 2: Safety Measures

PBO

(N=488)

Bari

(N=487)

ADA

(N=330)

PBO

(N=488)

Bari

(N=487)

ADA

(N=330)

TEAEs

231

(47.3)

257

(52.8)

168

(50.9)

293

(60.0)

345

(70.8)

221

(67.0)

Infections

87

(17.8)

106

(21.8)

66

(20.0)

132

(27.0)

174

(35.7)

110

(33.3)

   Herpes zoster

2

(0.4)

3

(0.6)

3

(0.9)

2

(0.4)

7

(1.4)

4

(1.2)

   Tuberculosis

0

0

1

(0.3)

0

0

1

(0.3)

SAEs‡

13

(2.7)

11

(2.3)

4

(1.2)

21

(4.3)

22

(4.5)

6

(1.8)

   Serious infections

5

(1.0)

4

(0.8)

0

7

(1.4)

5

(1.0)

2

(0.6)

Malignancy

1

(0.2)

0

0

3

(0.6)

2

(0.4)

0

   Breast cancer

0

0

0

1

(0.2)

1

(0.2)

0

   Lung squamous cell

0

0

0

0

1

(0.2)

0

   Non-melanoma skin    cancer

1

(0.2)

0

0

1

(0.2)

0

0

   Ovarian cancer

0

0

0

1

(0.2)

0

0

Lymphoproliferative disorder

0

0

1

(0.3)¥

0

0

1

(0.3)¥

Deaths

0

0

0

0

2

(0.4)

0

CTCAE Grade Shift (≥1 increase in grade from baseline)§

   Hemoglobin

97

(19.9)

92

(19.0)

43

(13.0)

117

(24.0)

127

(26.2)

56

(17.0)

   Lymphocyte

82

(16.8)

51

(10.5)

29

(8.8)

108

(22.2)

90

(18.6)

41

(12.4)

   ALT

53

(10.9)

84

(17.4)

56

(17.0)

80

(16.4)

121

(25.0)

77

(23.3)

Patients received stable background MTX throughout the study. Data are n (%) pts up to the time of rescue; ‡ SAEs defined by International Conference on Harmonization criteria; ¥Lymphoproliferative disorder was a transient neck adenopathy with no evidence of neoplasia; CTCAE = Common Terminology Criteria for Adverse Events;  § % of pts with laboratory grade shifts are based on n-observed for analyte

Disclosure: P. C. Taylor, UCB, GlaxoSmithKline, 2,UCB, Eli Lilly and Company, Pfizer, Galapagos, Merck, GlaxoSmithKline, AbbVie, Takeda, Bristol-Myers Squibb, 5; E. C. Keystone, Eli Lilly and Company, 2,Eli Lilly and Company, 5; D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Celgene, Daiichi, Eli Lilly and Company, Glapagos, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, 5,Director of Imaging Rheumatology bv, 4; Y. Tanaka, Mistubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, 2,Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, 8; T. Ishii, Eli Lilly and Company, 3,Eli Lilly and Company, 1; K. Emoto, Eli Lilly and Company, 3; L. Yang, Eli Lilly and Company, 3; V. Arora, Eli Lilly and Company, 3,Eli Lilly and Company, 1; C. L. Gaich, Eli Lilly and Company, 3; T. Rooney, Eli Lilly and Company, 1,Eli Lilly and Company, 3; D. E. Schlichting, Eli Lilly and Company, 1,Eli Lilly and Company, 3; W. Macias, Eli Lilly and Company, 1,Eli Lilly and Company, 3; S. de Bono, Eli Lilly and Company, 3; M. E. Weinblatt, Eli Lilly and Company, Pfizer, AbbVie, Vertex, 5.

To cite this abstract in AMA style:

Taylor PC, Keystone EC, van der Heijde D, Tanaka Y, Ishii T, Emoto K, Yang L, Arora V, Gaich CL, Rooney T, Schlichting DE, Macias W, de Bono S, Weinblatt ME. Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/baricitinib-versus-placebo-or-adalimumab-in-patients-with-active-rheumatoid-arthritis-ra-and-an-inadequate-response-to-background-methotrexate-therapy-results-of-a-phase-3-study/. Accessed .

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