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THU0175 Effects of Baricitinib on Multibiomarker Disease Activity Scores and Their Components in a Phase 2B Study in Moderate-to-Severe Rheumatoid Arthritis Patients
  1. P. Taylor1,
  2. M.C. Genovese2,
  3. E. Keystone3,
  4. M. Weinblatt4,
  5. J. Rancourt5,
  6. E. Nantz5,
  7. D. Schlichting5,
  8. S. Zuckerman5,
  9. W. Macias5
  1. 1Oxford Univ., Oxford, United Kingdom
  2. 2Stanford University, Palo Alto, United States
  3. 3Mt. Sinai Hosp., Toronto, Canada
  4. 4Brigham and Women's Hosp., Boston
  5. 5Eli Lilly & Company, Indianapolis, United States

Abstract

Background Baricitinib, an oral inhibitor of JAK1 and JAK2 signaling, improved the signs and symptoms in patients with active rheumatoid arthritis (RA) who were methotrexate inadequate responders (MTX-IR) in a double-blind, placebo (PBO) controlled study1.

Objectives To investigate how a quantitative, multibiomarker disease activity score (MBDA) and its individual components are affected by treatment with baricitinib 4 mg (n=50) once daily compared to PBO (n=79) during a 12 week treatment period in moderate-to-severe RA patients.

Methods Serum samples collected at baseline and Weeks 4 and 12 from patients in the study1 were shipped frozen to Crescendo Biosciences for analysis2. MBDA scores and changes in individual MBDA components were subjected to post-hoc statistical analyses.

Results At baseline, the proportion of patients with low, moderate, and high MBDA scores were similar in the 2 groups, as were median MBDA scores (PBO=44 vs. baricitinib 4 mg=47). Unlike PBO-treated patients, baricitinib 4 mg patients had decreased MBDA scores at 4 and 12 weeks compared to baseline (baricitinib 4 mg =35.5 and 37.0 (p<0.001) vs. PBO=46.0 and 45.0, respectively). At both 4 and 12 weeks of treatment and compared to PBO, baricitinib-treated patients had significant decreases in MBDA components including C-Reactive Protein (CRP), Matrix metalloproteinase (MMP)-3, serum amyloid A (SAA), soluble TNF receptor (TNF-RI), VCAM-1, and YKL-40 (human cartilage glycoprotein 39). Compared to PBO, there were no significant (p>0.05) changes for baricitinib-treated patients at either timepoint for epidermal growth factor (EGF), MMP-1, or vascular endothelial growth factor-A (VEGF-A). For baricitinib-treated patients versus PBO, at 4 but not 12 weeks, Interleukin-6 (IL-6) and resistin were significantly decreased and at 12 but not 4 weeks, leptin was significantly increased.

Table 1

Conclusions Consistent with other indices of disease activity1, the treatment of MTX-IR patients with baricitinib 4 mg once daily resulted in a reduction in the MBDA scores, apparent by 4 weeks. Decreases in MBDA scores and the components were present at both 4 and 12 weeks. Reduction in the levels of inflammatory markers beyond those associated with an acute phase response is apparent in these patients.

References

  1. Keystone E et al., Ann Rheum Dis 2015;74(2):333-340.

  2. Curtis JR et al., Art Care Res 2012:64(12):1794-1803.

Disclosure of Interest P. Taylor Consultant for: Pfizer, Eli Lilly & Company, M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, E. Keystone Grant/research support from: Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Meyers Squibb, F. Hoffman-La Roche Inc., Janssen Inc., Eli Lilly & Company, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB, Consultant for: Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Biotest, Bristol-Meyers Squibb, F. Hoffman-La Roche Inc., Genentech, Janssen Inc., Eli Lilly & Company, Merck, Pfizer Pharmaceuticals, UCB, Speakers bureau: Abbott Laboratories, Astrazeneca LP, Bristol-Meyers Squibb Canada, F. Hoffman-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, UCB, Amgen, M. Weinblatt Grant/research support from: Bristol-Meyers Squibb, Crescendo Bioscience, UCB, Consultant for: Abbvie, Amgen, Astra Zeneca, Bristol-Meyers Squibb, Crescendo Bioscience, Eli Lilly & Company, Pfizer, Roche, UCB, J. Rancourt Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, E. Nantz Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Zuckerman Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company

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