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FRI0124 Temporary interruptions of study drug during the baricitinib phase 3 rheumatoid arthritis program
  1. P Emery1,
  2. Y Tanaka2,
  3. TE Cardillo3,
  4. DE Schlichting3,
  5. S Beattie3,
  6. L Chen3,
  7. TP Rooney3,
  8. JS Smolen4
  1. 1Leeds MSK Biomed/Chapel Allerton Hosp, Leeds, United Kingdom
  2. 2University of Occupational & Environmental Health, Kitakyushu, Japan
  3. 3Eli Lilly and Company, Indianapolis, United States
  4. 4Medical University of Vienna, Vienna, Austria

Abstract

Background Temporary interruption of RA therapy is common in clinical practice; therefore, rapid clearance and low immunogenicity may be useful DMARD attributes. Baricitinib (bari) is a non-biologic Janus kinase (JAK) 1 /JAK2 selective inhibitor with a pharmacokinetic half-life in RA patients of approximately 13 hours. It has demonstrated improved clinical efficacy compared to MTX, adalimumab and placebo (pbo) with a satisfactory safety profile when administered once daily to RA patients in 4 completed Phase 3 studies.

Objectives These analyses aimed to characterize temporary interruptions of study drug during these studies and explore the kinetics of RA symptoms during and following interruption.

Methods During bari Phase 3 studies, investigators were required to document temporary interruptions of study drug, including timing, reason and duration, using electronic case report forms. In 2 studies, patients recorded RA symptoms (duration and severity of morning joint stiffness, worst tiredness and worst joint pain) daily for 12 weeks. Post hoc analyses investigated changes in these scores among patients randomized at least 7 days prior to interruption, having an interruption that lasted at least 3 days, and retreated.

Results Across the 3 pbo-controlled studies, interruptions occurred in a larger proportion of patients with bari than pbo only in the biologic DMARD-inadequate responder (IR) study RA-BEACON. In the 2 active comparator-controlled studies, the lowest rates of interruption were in the bari monotherapy arm of the DMARD-naïve MTX-controlled RA-BEGIN study, and proportions were similar for bari and adalimumab in the MTX-IR study, RA-BEAM (Table 1). Adverse events (predominantly non-serious, mild or moderate infections, most commonly of the respiratory tract) were the most frequent reason for interruption. Few patients interrupted for the reason of abnormal laboratory results. Most interruptions lasted for 2 weeks or less; in RA-BEAM, interruptions appeared shorter in duration for bari than for adalimumab. Diary measures indicated modest symptom increases during interruption compared to the last pre-interruption value, with a return to pre-interruption values or better after resumption of study drug (Table 2).

Conclusions Consistent with its pharmacologic properties, brief temporary interruptions of bari during Phase 3 studies were associated with minor increases in RA symptoms, which resolved following resumption of therapy. A small molecule with a short half-life may offer advantages over injectable biologic therapies with respect to drug interruption for clinical cause in RA patients.

Disclosure of Interest P. Emery Consultant for: Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, Eli Lilly and Company, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, janssen, Eli Lilly and Company, GlaxoSmithKline, T. Cardillo Employee of: Eli Lilly and Company, D. Schlichting Employee of: Eli Lilly and Company, S. Beattie Employee of: Eli Lilly and Company, L. Chen Employee of: Eli Lilly and Company, T. Rooney Employee of: Eli Lilly and Company, J. Smolen: None declared

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