Background Baricitinib (BARI), an oral inhibitor of Janus kinase (JAK) 1 and JAK 2, is being developed for the treatment of rheumatoid arthritis (RA). RA-BEGIN was a phase 3 double-blind, three-arm multicentre study of BARI administered as monotherapy or in combination with methotrexate (MTX) to patients (pts) with early active RA who had no or limited treatment with DMARDs. Methotrexate (MTX) monotherapy was the active comparator.
Objectives To evaluate the proportion of pts with structural damage progression, defined as change from baseline (CFB) greater than the smallest detectable change (SDC) in mTSS at week (wk) 52, depending on their disease state as measured by DAS28-CRP.
Methods Pts were classified into two groups based on DAS28-CRP. Group A included pts who achieved sustained DAS28-CRP ≤3.2 at weeks 16, 20 and 24. Pts who did not achieve DAS28-CRP ≤3.2 consecutively at weeks 16, 20 and 24 and pts with missing DAS28-CRP at any of those 3 visits were included in Group B. The proportion of pts with CFB mTSS > SDC at wk 52 was estimated for each treatment arm for the two defined groups of response. The SDC in mTSS in the RA-BEGIN population at wk 52 was 1.4. Missing mTSS at wk 52 were imputed using linear extrapolation based on baseline data and the most recent radiographic data prior to the missed radiograph. No formal statistical tests were performed and comparisons are merely descriptive. All analyses were post-hoc.
Results Out of the 584 pts of the modified-ITT population (all randomised pts who received at least 1 dose of study drug) in the RA-BEGIN study, 212 were classified in Group A: 21.4% (45/210), 42.1% (67/159), and 46.5% (100/215) for MTX, BARI and BARI+MTX, respectively. The odds ratios for sustained DAS28-CRP ≤3.2 response (weeks 16, 20 and 24) to BARI and BARI+MTX vs. MTX, were respectively 2.8 (95% CI 1.7–4.4) and 3.3 (95% CI 2.1–5.1). Pts classified in Group A maintained an adequate level of response up to wk 52. Further, pts in Group A (sustained DAS28-CRP ≤3.2) on either BARI + MTX or BARI, were less likely to show structural progression than patients who achieved sustained DAS28-CRP ≤3.2 on MTX. Pts in Group B on MTX or BARI monotherapy were more likely to show structural progression than patients who did not achieve a sustained DAS28-CRP ≤3.2 response on BARI + MTX (Figure 1).
Footnote: Group A: Patients who achieved sustained DAS28-CRP ≤3.2 (NRI) at weeks 16, 20 and 24 (N=212); Group B: Complement group
Conclusions In patients who achieved sustained low DAS28-CRP scores, progression rates compared to MTX were reduced to a similar degree with BARI as monotherapy or in combination with MTX. Compared to MTX in patients who did not achieve sustained low DAS28-CRP scores, progression rates were reduced most markedly with combination therapy.
Disclosure of Interest D. van der Heijde Consultant for: Abbvie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Company, Galapagos, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, P. Durez: None declared, G. Schett: None declared, E. Naredo: None declared, M. Østergaard Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth, G. Meszaros Employee of: Eli Lilly & Company, N. Bello Employee of: Eli Lilly & Company, I. De la Torre Employee of: Eli Lilly and Company, P. Lopez-Romero Employee of: Eli Lilly & Company, D. Schlichting Employee of: Eli Lilly and Company, E. Nantz Employee of: Eli Lilly and Company, R. Fleischmann Consultant for: Abbvie, Amgen, Astra Zeneca, BMS, Celgene, Janssen, Eli Lilly and Company, Novartis, Roche, Sanofi-Aventis, Pfizer, UCB