18A113

Durability, Maintenance and Effects of Dose Reduction Following Prolonged Treatment with Baricitinib

Author(s)

Josef S. Smolen1, Maxime Dougados2, Tsutomu Takeuchi3, Mark C. Genovese 4, Boulos Haraoui5, Rena Klar6, Arthur Kavanaugh7, Ricardo Blanco Alonso8, Jean Dudler9; Peter C. Taylor10, Peter Nash11, Cristiano AF Zerbini 12, Patrick Durez13, Georg Pum14, Subhashini Arthanari15, Francesco De Leonardis16, Ronald van Vollenhoven17, Erica Tierney (Presenter only)18

Department(s)/Institutions

1Medical University of Vienna, Vienna, Austria; 2Hôpital Cochin, Paris Descartes University, Paris, France; 3Keio University School of Medicine, Tokyo, Japan; 4Stanford University Medical Center, Palo Alto, California, USA; 5Centre Hospitalier de l'Université de Montréal, Montréal, Canada; 6IQVIA, Durham, NC, USA; 7UC San Diego School of Medicine, La Jolla, California, USA; 8Hospital Universitario Valdecilla, Cantabria, Spain; 9Hôpital Cantonal, Fribourg, Switzerland; 10University of Oxford, Oxford, UK; 11University of Queensland, Australia; 12Centro Paulista de Investigação Clinica, Brazil; 13Cliniques Universitaires Saint-Luc, Belgium; 14Eli Lilly & Company, Austria; 15Eli Lilly & Company, UK; 16Eli Lilly & Company, Geneva, Switzerland; 17Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, Netherlands; 18Presenting on behalf of the authors

Introduction

Baricitinib (BARI) is a reversible oral JAK inhibitor with selectivity for JAK1/JAK2 for active Rheumatoid Arthritis.

Aims/Background

It is clinically relevant to understand the durability and maintenance of response to baricitinib (BARI), a selective Janus kinase (JAK)1/JAK2 inhibitor, over prolonged use, and the dose tapering strategies available after achieving disease control.

Method

Upon completion of BARI Phase 3 originating studies (OS) (RA-BEGIN, RA-BEAM, RA-BUILD, and RA-BEACON), patients could enter the long term extension (LTE) study, RA-BEYOND. Durability of response was evaluated as proportion of patients achieving SDAI≤11 in the OS and through 96 weeks in the LTE. Maintenance of response was evaluated as proportion of patients who had responded to BARI at entry into LTE and maintained the response at Week 96. Within RA-BEYOND, patients who received BARI 4-mg for ≥15 months and who achieved sustained LDA (CDAI≤10) or remission (CDAI≤2.8) at 2 consecutive visits, were re-randomised in a blinded manner to continue BARI 4-mg or step down to 2-mg.

Results

Durability of response was evident as response rates were higher 96 weeks after entry into RA-BEYOND as compared to Week 12 of the OS. Most responders at entry into LTE maintained their response through Week 96 (data not shown).
Dose reduction to BARI 2-mg once daily (QD) resulted in small increases in disease activity up to Week 48, as compared to BARI 4-mg. CDAI≤10 rates at Week 48 were 68.2 for BARI 2-mg (vs 80.8 for 4-mg, p≤0.01]). By Week 48, a majority of patients (in both the groups) recaptured (data not shown) or maintained the state of LDA or remission.

Conclusions

Effectiveness of BARI, as measured by durability and maintenance of response, is maintained with prolonged therapy. In line with the observations from OS, 4-mg QD is the most efficacious dose. Dose tapering to 2-mg QD may be a reasonable consideration according to treatment goals and responses of an individual patient.