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 Takeuchi 2, Douglas E. Schlichting3, William L. Macias3, Terence
Rooney3, Sirel Gurbuz 3, 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)

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
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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 MTX Bari 4 mg Bari 4 mg MTX Bari 4 mg Bari 4 mg

Measures + MTX + MTX
(N=210) (N=159) (N=210) (N=159)
(N=215) (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**

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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 MTX Bari 4 mg Bari 4 mg + MTX

Measures through Wk
24 (N=210) (N=159) (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
0 0 1
cancer

Adrenocortical
0 0 1
carcinoma

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.

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 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). http://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
January 17, 2017.

ACR Meeting Abstracts - http://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/

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