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.
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Wk 12 |
Wk 24 |
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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) |
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ACR20 |
59 |
79*** |
77*** |
62 |
77** |
78*** |
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ACR50 |
33 |
55*** |
60*** |
43 |
60** |
63*** |
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ACR70 |
16 |
31*** |
34*** |
21 |
42*** |
40*** |
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DAS28-CRP ≤3.2 |
30 |
47*** |
56*** |
38 |
57** |
60*** |
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DAS28-CRP <2.6 |
16 |
28** |
36*** |
24 |
40** |
41*** |
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DAS28-ESR ≤3.2 |
15 |
21 |
34*** |
23 |
36* |
39** |
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DAS28-ESR <2.6 |
7 |
13* |
18** |
12 |
21* |
25** |
|
CDAI ≤10 |
30 |
43** |
51*** |
39 |
60*** |
59*** |
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CDAI ≤2.8 |
7 |
14* |
19*** |
11 |
21* |
22** |
|
SDAI ≤11 |
30 |
45** |
54*** |
40 |
62*** |
61*** |
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SDAI ≤3.3 |
6 |
14* |
20*** |
11 |
22** |
23** |
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HAQ-DI MCID ≥0.22 |
67 |
86*** |
80** |
70 |
81* |
78 |
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FACIT-F MCID ≥3.56 |
64 |
79** |
72 |
65 |
75* |
70 |
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Data are % pts achieving response (NRI); *p≤.05, **p≤.01, ***p≤.001 vs. MTX |
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Table 2 Safety Measures through Wk 24 |
MTX (N=210) |
Bari 4 mg (N=159) |
Bari 4 mg + MTX (N=215) |
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TEAEs |
137 (65.2) |
101 (63.5) |
145 (67.4) |
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Infections* |
58 (27.6) |
43 (27.0) |
74 (34.4) |
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Herpes Zoster |
1 (0.5) |
3 (1.9) |
3 (1.4) |
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SAEs |
8 (3.8) |
5 (3.1) |
8 (3.7) |
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Serious infections |
3 (1.4) |
1 (0.6) |
4 (1.9) |
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Malignancy |
0 |
0 |
2 (0.9) |
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Non-melanoma skin cancer |
0 |
0 |
1 |
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Adrenocortical carcinoma |
0 |
0 |
1 |
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Deaths |
1 (0.5) |
0 |
0 |
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CTCAE Grade Shift (≥1 increase in grade from baseline)** |
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Hemoglobin |
51 (24.8) |
45 (28.3) |
66 (31.1) |
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Lymphocyte |
45 (21.8) |
15 (9.4) |
38 (17.9) |
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ALT |
54 (26.2) |
19 (11.9) |
52 (24.5) |
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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 |
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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 November 23, 2020.« 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/