Session Information
Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Baricitinib (BARI), is an oral Janus kinase (JAK)1/JAK2 selective inhibitor for treatment of patients with moderately to severely active RA. RA-BEAM was a phase 3 study in patients with RA and an inadequate response to MTX (MTX-IR) in which BARI demonstrated significant improvements in ACR20 response rates and DAS28-CRP compared to placebo (PBO) and adalimumab (ADA). This abstract examines the effects of baricitinib on disease activity scores and the improvement of disease activity compared to PBO and ADA utilizing CDAI, which does not include acute phase reactants and only uses clinical measures (adding physician and patient global assessments, to tender and swollen joint counts).
Methods: In RA-BEAM, 1305 patients were treated with PBO (N=488), ADA (N=330) or BARI 4 mg (N=487) and continued to receive background MTX. CDAI for the three treatment groups was determined at baseline (mean [SD] of 37.6 [12.8], 38.1 [12.0], 37.9 [13.0] for PBO, BARI and ADA, respectively) and at each visit post baseline for up to 24 weeks, and for the BARI and ADA groups for up to 52 weeks. In this analysis, CDAI and the improvement from baseline to Weeks 12 and 24 were compared between treatment groups using analysis of covariance (ANCOVA). The proportions of patients reaching a disease activity threshold and improvement threshold at Weeks 12 and 24 were compared between treatment groups using logistic models. Analyses were not adjusted for multiplicity. Missing values were imputed using modified last observation carried forward.
Results: At baseline, across all treatment arms, 91% of patients had high disease activity and 9% had moderate disease activity. Treatment with BARI resulted in significantly lower mean disease activity at Weeks 12 and 24 than PBO (p<0.001 at both Weeks 12 and 24) and ADA (p=0.008, Week 12; p=0.035, Week 24). Fewer patients treated with BARI (16.4%) remained in high disease activity at Week 24 compared to PBO (47.6%, p<0.001) and ADA (22.9%, p=0.017). Patients treated with BARI had significantly greater improvement in the mean disease activity compared to PBO (p<0.001) and ADA (p=0.023) at 24 weeks. A larger proportion of patients receiving BARI (86.2%) were able to achieve at least a 12-point reduction in CDAI, the minimal clinically important difference in disease activity improvement, by Week 24 compared to patients receiving PBO (52.4%, p<0.001) or ADA (77.5%, p=0.001) (Table and graphs).
Conclusion: In MTX-IR RA patients with moderate to severe disease activity, BARI significantly reduced the overall disease activity compared to PBO and ADA.
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CDAI: Disease Activity from Baseline to Weeks 12 and 24 |
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Week 12 |
Week 24 |
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Placebo (N=488) |
BARI 4-mg (N=487) |
ADA (N=330) |
Placebo (N=488) |
BARI 4-mg (N=487) |
ADA (N=330) |
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CDAI |
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LS Mean (SE) |
24.7 (0.6) |
15.6 (0.7)***++ |
18.1 (0.8)*** |
23.9 (0.7) |
13.4 (0.7)***+ |
15.5 (0.8)*** |
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% Patients with HDA (CDAI >22) |
49.9 |
21.1*** |
26.2*** |
47.6 |
16.4***+ |
22.9*** |
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% Patients with MDA (10< CDAI ≤22) |
32.8 |
37.5 |
39.6 |
31.3 |
31.3 |
28.4 |
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% Patients with LDA§ (2.8< CDAI ≤10) |
15.5 |
32.9***+ |
27.4*** |
16.9 |
36.4*** |
36.9*** |
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% Patients with remission (CDAI ≤2.8) |
1.9 |
8.5*** |
6.7*** |
4.1 |
15.9*** |
11.9*** |
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Improvement in CDAI |
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LS Mean Change from baseline (SE) |
-12.9 (0.6) |
-22.0 (0.6)***++ |
-19.5 (0.7)*** |
-13.6 (0.6) |
-24.2 (0.6)***+ |
-22.1 (0.7)*** |
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LS Mean % Improvement (SE) |
33.1 (1.5) |
58.3 (1.5)***++ |
51.9 (1.8)*** |
35.1 (1.7) |
64.1 (1.7)***+ |
58.9 (2.0)*** |
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% Patients with CDAI improvement ≥6 |
71.1 |
91.8*** |
88.6*** |
71.5 |
92.9*** |
90.1*** |
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% Patients with CDAI improvement ≥12 |
51.4 |
83.1***+++ |
70.1*** |
52.4 |
86.2***++ |
77.5*** |
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***p<0.001 vs. placebo; +p<0.05, ++p<0.01, +++p<0.001 vs. adalimumab using ANCOVA after adjusting for baseline value, region, and joint erosion status for the CDAI improvement outcome; adjusting for region and joint erosion status for the CDAI actual score; and using logistic regression models after adjusting for region and joint erosion status for the proportions of patients reaching a disease activity threshold and improvement threshold. §p-values for between treatment comparisons were based on CDAI ≤10.ANCOVA=Analysis of Covariance; ADA=adalimumab; BARI=baricitinib; CDAI=Clinical Disease Activity Index; HDA=high disease activity; LDA=low disease activity; LS=least squares; MDA=moderate disease activity; SE=standard error |
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To cite this abstract in AMA style:
Nash P, Pope JE, Cardoso A, Casillas M, Schlichting DE, Zhu B, Beattie SD, Smolen JS. Reduction in Disease Activity in Patients with RA and an Inadequate Response to MTX: Baricitinib Compared to Adalimumab and Placebo [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/reduction-in-disease-activity-in-patients-with-ra-and-an-inadequate-response-to-mtx-baricitinib-compared-to-adalimumab-and-placebo/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduction-in-disease-activity-in-patients-with-ra-and-an-inadequate-response-to-mtx-baricitinib-compared-to-adalimumab-and-placebo/