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THU0193 Response To Baricitinib at 4 Weeks Predicts Response at 12 and 24 Weeks in Patients with Rheumatoid Arthritis: Results from Two Phase 3 Studies
  1. M. Weinblatt1,
  2. P. Taylor2,
  3. Y. Tanaka3,
  4. E. Keystone4,
  5. M. Schiff5,
  6. R. Fleischmann6,
  7. L. Yang7,
  8. V. Arora7,
  9. S. de Bono7,
  10. T. Holzkaemper7,
  11. D. Schlichting7,
  12. T. Takeuchi8
  1. 1Brigham and Women's Hospital, Boston, United States
  2. 2Univ of Oxford, Headington, United Kingdom
  3. 3Univ Occup Environ Health, Fukuoka, Japan
  4. 4Mt Sinai Hospital, Toronto, Ontario, Canada
  5. 5Univ Colorado Hospital Rheum, Greenwood Village
  6. 6Univ Texas SW Medical Center, Dallas
  7. 7Eli Lilly & Co., Indianapolis, United States
  8. 8Keio Univ, Tokyo, Japan

Abstract

Background Baricitinib (bari), a JAK1 and JAK2 inhibitor, showed significant improvements across multiple measures of disease activity as early as week (wk) 1 that were maintained through wk 52 in ph 3 studies of patients (pts) with active RA.1,2

Objectives To determine if, in bari-treated pts, early changes in disease activity predicted later achievement of low disease activity (LDA) or remission.

Methods 1305 pts with inadequate response to methotrexate (MTX) were randomized in RA-BEAM (3:3:2, oral PBO/4 mg bari QD/SC injection adalimumab [ADA] Q2W, 52 wks); 584 MTX-naïve pts were randomized in RA-BEGIN (4:3:4, oral MTX QW/4 mg bari QD/4 mg bari QD+MTX QW, 52 wks). Improvement from baseline (BL) to wk 4 was used to predict LDA or remission defined by Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) at wks 12/24 (bari 4 mg arm, both studies). Early responder and early nonresponder were predefined as Clinical Disease Activity Index (CDAI) improvement ≥6 and <6, respectively, at wk 4.

Results Compared to PBO or ADA (RA-BEAM) or MTX (RA-BEGIN), treatment with bari was associated with rapid decrease in DAS28 and CDAI from wk 1.1,2 By wk 4, 86% (RA-BEAM) and 85% (RA-BEGIN) of bari pts had a CDAI decrease ≥6. In both studies, LDA/remission rates at wks 12/24 were higher in pts with CDAI improvement ≥6 compared to pts with CDAI improvement <6 from BL to wk 4 (Table). Negative predictive values (NPV) for remission at wks 12/24 associated with CDAI improvement <6 from BL to wk 4 exceeded 90%, indicating that pts with CDAI improvement <6 were highly unlikely to achieve remission; NPV for LDA exceeded 80%.

Table 1.

LDA and remission After 12 and 24 weeks of 4 mg baricitinib treatment in RA-BEAM and RA-BEGIN

Conclusions In RA-BEAM/RA-BEGIN, lack of early clinical response to bari 4 mg (failure to achieve CDAI improvement ≥6 at 4 wks) was associated with low rates of LDA/remission at wks 12/24. These results are consistent with similar analyses from previous ph 3 studies of bari.3 The majority of bari pts had improvement in CDAI ≥6 at wk 4; these decreases were associated with improved clinical responses at wks 12/24. Early identification of pts (4 wks) who are not likely to achieve LDA/remission may be useful in tailoring therapy to individual pts.

  1. Taylor PC et al. Arthritis Rheumatol. 2015; 67 (suppl 10).

  2. Fleischmann R et al. Arthritis Rheumatol. 2015; 67 (suppl 10).

  3. Kremer J et al. Arthritis Rheumatol. 2015; 67 (suppl 10).

Disclosure of Interest M. Weinblatt Grant/research support from: Crescendo Bioscience, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, Crescendo Bioscience, P. Taylor Grant/research support from: UCB, GlaxoSmithKline, Celgene, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Merck, Pfizer, Takeda, USB, Y. Tanaka Grant/research support from: Mistubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, E. Keystone Grant/research support from: Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Company, F. Hoffmann-La Roche Inc, Janssen Inc, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB, Consultant for: Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Eli Lilly and Company, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Merck, Pfizer Pharmaceuticals, UCB, Speakers bureau: Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, UCB, Amgen, M. Schiff Grant/research support from: Eli Lilly and Company, Consultant for: Eli Lilly and Company, R. Fleischmann Grant/research support from: Eli Lilly and Company, Pfizer, Consultant for: Eli Lilly and Company, Pfizer, L. Yang Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, V. Arora Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Holzkaemper Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, D. Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Takeuchi Grant/research support from: Eli Lilly and Company, Chugai Pharmaceutical Co,. Ltd, Consultant for: Eli Lilly and Company

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