ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 1045

Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results

Roy Fleischmann1, Tsutomu Takeuchi2, Douglas E. Schlichting3, William L. Macias3, Terence Rooney3, Sirel Gurbuz3, Ivaylo Stoykov3, Scott D. Beattie3, Wen-Ling Kuo3 and M Schiff4, 1Rheumatology, Metroplex Clinical Research Center, Dallas, TX, 2Keio University School of Medicine, Tokyo, Japan, 3Eli Lilly and Company, Indianapolis, IN, 4School of Medicine, University of Colorado, Denver, CO

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Clinical research, Janus kinase (JAK), methotrexate (MTX) and rheumatoid arthritis (RA)

  • Tweet
  • Email
  • Print
Session Information

Date: Sunday, November 8, 2015

Session Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy II: Small Molecular Targeted Therapies

Session Type: ACR Concurrent Abstract Session

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

Background/Purpose:

In 2 completed phase 3 studies, baricitinib (bari) improved disease activity with a satisfactory safety profile in patients (pts) with moderately-to-severely active RA who were inadequate responders to either conventional synthetic1 or biologic2DMARDs. This abstract reports results from a phase 3 study of bari administered as monotherapy or in combination with methotrexate (MTX) to pts with early active RA who had limited or no prior treatment with DMARDs. MTX monotherapy was the active comparator.

Methods: Pts with active RA (TJC & SJC ≥6, hsCRP ≥3.6 mg/L) and no previous DMARD treatment other than ≤3 doses of MTX were randomized 4:3:4 to MTX, bari 4 mg once daily  (QD; bari monotherapy), or bari 4 mg QD + MTX for up to 52 wks. MTX dose, with or without bari, was up-titrated from 10 to 20 mg once weekly over 8 weeks (wks). Rescue was not allowed prior to Wk 24, the time point for primary and all major secondary efficacy endpoints.  The primary objective evaluated non-inferiority of bari 4 mg monotherapy to MTX on ACR20 at Wk 24 (using a 12% margin).

Results: Of 584 randomized pts, 87%, 91%, and 89% of pts completed Wk 24 in the MTX, bari 4 mg monotherapy, and bari 4 mg + MTX groups, respectively. ACR20 response at Wk 24 was higher with bari 4 mg monotherapy vs. MTX (77% vs. 62%, p≤.01). Compared to MTX, bari 4 mg monotherapy produced significantly greater improvements in multiple secondary measures of disease activity (Table 1), many as early as Wk 1. MTX in combination with bari 4 mg did not appear to increase the benefit observed with bari 4 mg monotherapy. Clinical remission was seen in a significantly higher proportions of pts treated with bari 4 mg alone or in combination with MTX compared to MTX alone (Table 1). Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were similar across groups (Table 2). Through 24 wks, 2 (1.0%), 6 (3.8%) and 14 (6.5%) pts discontinued the study because of an adverse event in the MTX, bari 4 mg monotherapy, and bari 4 mg + MTX groups, respectively.  No GI perforations occurred during the study.  Laboratory abnormalities were generally less frequent in the bari 4 mg group compared to either the MTX or bari 4 mg + MTX groups (Table 2).

Conclusion:

In pts with early RA, all treatment groups experienced improvements in disease activity with bari 4 mg monotherapy producing significantly larger and more rapid improvements and higher rates of clinical remission compared to MTX monotherapy, with a satisfactory safety profile. MTX addition to bari 4 mg did not increase the benefit observed with bari monotherapy, while it appeared to increase the frequency of laboratory abnormalities.

 

Wk 12

Wk 24

Table 1 Efficacy Measures

MTX

(N=210)

Bari 4 mg

(N=159)

Bari 4 mg + MTX

(N=215)

MTX

(N=210)

Bari 4 mg

(N=159)

Bari 4 mg + MTX

(N=215)

ACR20

59

79***

77***

62

77**

78***

ACR50

33

55***

60***

43

60**

63***

ACR70

16

31***

34***

21

42***

40***

DAS28-CRP ≤3.2

30

47***

56***

38

57**

60***

DAS28-CRP <2.6

16

28**

36***

24

40**

41***

DAS28-ESR ≤3.2

15

21

34***

23

36*

39**

DAS28-ESR <2.6

7

13*

18**

12

21*

25**

CDAI ≤10

30

43**

51***

39

60***

59***

CDAI ≤2.8

7

14*

19***

11

21*

22**

SDAI ≤11

30

45**

54***

40

62***

61***

SDAI ≤3.3

6

14*

20***

11

22**

23**

HAQ-DI MCID ≥0.22

67

86***

80**

70

81*

78

FACIT-F MCID ≥3.56

64

79**

72

65

75*

70

Data are % pts achieving response (NRI); *p≤.05, **p≤.01, ***p≤.001 vs. MTX

Table 2 Safety Measures through Wk 24

MTX

(N=210)

Bari 4 mg

(N=159)

Bari 4 mg + MTX

(N=215)

TEAEs

137 (65.2)

101 (63.5)

145 (67.4)

   Infections*

58 (27.6)

43 (27.0)

74 (34.4)

      Herpes Zoster

1 (0.5)

3 (1.9)

3 (1.4)

SAEs

8 (3.8)

5 (3.1)

8 (3.7)

   Serious infections

3 (1.4)

1 (0.6)

4 (1.9)

Malignancy

0

0

2 (0.9)

Non-melanoma skin cancer

0

0

1

Adrenocortical carcinoma

0

0

1

Deaths

1 (0.5)

0

0

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

    Hemoglobin

51 (24.8)

45 (28.3)

66 (31.1)

    Lymphocyte

45 (21.8)

15 (9.4)

38 (17.9)

    ALT

54 (26.2)

19 (11.9)

52 (24.5)

Data are n(%) pts. CTCAE = Common Terminology Criteria for Adverse Events. *1 Pneumocystis carinii pneumonia and 1 esophageal candidiasis were reported (bari 4 mg + MTX). **% of pts with laboratory grade shifts are based on n-observed for analyte.

 

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


Disclosure: R. Fleischmann, Pfizer Inc, 2,Pfizer Inc, 5,Eli Lilly and Company, 2,Eli Lilly and Company, 5; T. Takeuchi, Chugai Pharmaceutical Co,. Ltd., 2,Eli Lilly and Company, 2,Eli Lilly and Company, 5; D. E. Schlichting, Eli Lilly and Company, 1,Eli Lilly and Company, 3; W. L. Macias, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. Rooney, Eli Lilly and Company, 1,Eli Lilly and Company, 3; S. Gurbuz, Eli Lilly and Company, 1,Eli Lilly and Company, 3; I. Stoykov, Eli Lilly and Company, 1,Eli Lilly and Company, 3; S. D. Beattie, Eli Lilly and Company, 1,Eli Lilly and Company, 3; W. L. Kuo, Eli Lilly and Company, 1,Eli Lilly and Company, 3; M. Schiff, Eli Lilly and Company, 2,Eli Lilly and Company, 5.

To cite this abstract in AMA style:

Fleischmann R, Takeuchi T, Schlichting DE, Macias WL, Rooney T, Gurbuz S, Stoykov I, Beattie SD, Kuo WL, Schiff M. Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/baricitinib-methotrexate-or-baricitinib-plus-methotrexate-in-patients-with-early-rheumatoid-arthritis-who-had-received-limited-or-no-treatment-with-disease-modifying-anti-rheumatic-drugs-dmards-p/. Accessed July 1, 2022.
  • Tweet
  • Email
  • Print

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/baricitinib-methotrexate-or-baricitinib-plus-methotrexate-in-patients-with-early-rheumatoid-arthritis-who-had-received-limited-or-no-treatment-with-disease-modifying-anti-rheumatic-drugs-dmards-p/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies