Abstract
Background/Aims
Baricitinib (BARI) is an oral, reversible, selective JAK1/2 inhibitor. Treatment with once-daily oral BARI resulted in low rates of radiographic progression for up to 2 years in patients with rheumatoid arthritis (RA). Here, we evaluate the radiographic progression of structural joint damage in patients with RA over 5 years of treatment with BARI.
Methods
This included patients who completed three Phase 3 trials, RA-BEGIN (DMARD-naive), RA-BUILD (csDMARD-IR), or RA-BEAM (MTX-IR), and enrolled in long-term extension study, RA-BEYOND. Patients receiving blinded BARI at the conclusion of Phase 3 trials remained on that dose (2mg/4mg, once daily) in RA-BEYOND. At 52 weeks, DMARD-naive patients receiving methotrexate(MTX) or combination therapy(BARI 4mg+MTX) were switched to BARI 4mg monotherapy; MTX-IR patients receiving adalimumab(ADA) were switched to BARI 4mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo(PBO) were switched to BARI 4mg on background csDMARD. Analysis population included patients who had baseline and at least one radiograph collected after 2 years. Radiographic progression of structural joint damage (Years 3-5) was determined by changes from baseline in van der Heijdemodified Total Sharp Score(ΔmTSS), erosion score, and joint space narrowing. Proportion of patients showing no progression was assessed based on change from baseline mTSS(ΔmTSS) from originating study, using thresholds of 0.5 or smallest detectable change(SDC). Mixedmodel repeatedmeasures and logistic regression models were used to analyze continuous variables and categorical variables, respectively; linear extrapolation was used for imputation of missing data(maximum of 1 year).
Results
82.6% (2125/2573) of patients entered long-term extension study. Among DMARD-naive patients, those on initial BARI monotherapy or in combination with MTX had significantly slower radiographic progression(ΔmTSS) versus those on initial MTX at Years 3, 4, 5 (p ≤ 0.05). They had significantly fewer erosions at these time points (p ≤ 0.05). A greater proportion of patients who received initial BARI therapy and BARI+MTX had no radiographic progression versus initial MTX monotherapy using thresholds of 0.5 (p ≤ 0.05). Among MTX-IR patients, those on initial BARI treatment had slower radiographic progression compared to PBO and results were comparable to those on initial ADA treatment at Years 3, 4, 5. A greater proportion of patients who received initial BARI therapy had no radiographic progression versus initial PBO using thresholds of SDC (p ≤ 0.05). Among csDMARD-IR patients, although differences between groups were small, patients on initial BARI 4mg had slowest radiographic progression compared to initial PBO and initial BARI 2mg. At least 74% of the structure data used in the analyses are based on observed data.
Conclusion
Treatment with once-daily oral BARI maintained low rates of radiographic progression for up to 5 years in different patient populations with RA.
Disclosure
D.M.F.M. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi Sankyo, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma. C.E. Kartman: Shareholder/stock ownership; Eli Lilly and Company. L. Xie: Shareholder/stock ownership; Eli Lilly and Company. S. Beattie: Shareholder/stock ownership; Eli Lilly and Company. D.E. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, and Sanofi. Y. Tanaka: Member of speakers’ bureau; AbbVie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, Takeda, UCB, and YL Biologics. Grants/research support; AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, and Taisho-Toyama and Takeda. R. Fleischmann: Consultancies; AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB.
Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis
