Patients with rheumatoid arthritis (RA) taking baricitinib after an inadequate response to methotrexate showed significant clinical improvements compared with patients with RA taking adalimumab or placebo, according to results from a recent trial published in The New England Journal of Medicine.
Peter C. Taylor, PhD, from the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the Kennedy Institute of Rheumatology, University of Oxford in the United Kingdom, and colleagues performed a double-blind, placebo-controlled, active-controlled, phase 3 trial in 1307 patients taking baricitinib (4 mg once daily), adalimumab (40 mg every other week), or placebo in addition to methotrexate background therapy.
Patients were admitted to the trial after 12 weeks or more of inadequate response to methotrexate and assigned a regimen in a 3:3:2 ratio for placebo, baricitinib, and adalimumab treatment, with the placebo group switching over to baricitinib treatment after 24 weeks.
High-Yield Data Summary
- Combination baricitinib plus methotrexate was superior to adalimumab plus methotrexate in achieving the study end point, despite the latter being a current standard-of-care treatment in this patient population.
End point measurements used by researchers in the trial included a 20% clinical improvement according to American College of Rheumatology criteria (ACR20), Health Assessment Questionnaire-Disability Index (HAQ-DI), Simplified Disease Activity Index (SDAI) (12 weeks), Disease Activity Score for 28 joints (DAS28) and use of C-reactive protein (DAS28-CRP), and van der Heijde modification of total Sharp score (mTSS) indicating radiographic progression of joint damage (24 weeks).
“Baricitinib showed significant clinical benefits as compared with placebo at week 12 along with greater efficacy than adalimumab according to ACR20 response rate and diminished disease activity according to DAS28-CRP,” Dr Taylor and colleagues wrote in their study. “As compared with placebo, significant inhibition of radiographic progression of disease was observed at week 24 with both baricitinib and adalimumab.”
Specifically, 70% of patients taking baricitinib had an ACR20 response compared with 40% of patients in the placebo group (P <.001), whereas 60% of patients in the adalimumab group showed an increased ACR20 response rate compared with 70% of patients in the baricitinib group (P =.014). At 24 weeks, patients in the baricitinib group showed a 0.41 change in mTSS from baseline compared with a 0.90 change in mTSS from baseline in the placebo group (P <.001).
Summary and Clinical Applicability
“Baricitinib was associated with reductions in neutrophil counts and increases in levels of creatinine and low-density lipoprotein cholesterol,” Dr Taylor and colleagues wrote.
The researchers noted adverse outcomes in the baricitinib and adalimumab groups were greater at 24 weeks compared with the placebo group. Dr Taylor and colleagues reported 5 cases of cancer in the trial, with 2 patients in the baricitinib group and 3 patients in the placebo group.
“Our study showed that for the outcome measure used as the primary end point, the combination of baricitinib plus methotrexate was superior to adalimumab plus methotrexate, the latter being a current standard-of-care treatment in this patient population.”
- Not all patients had a response to synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs).
- Conventional synthetic DMARDs were less effective and had a slower onset compared to biologic DMARDs.
- There were limitations to biologic drugs parental delivery.
This study was supported by Eli Lilly and Incyte.
Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376:652-662. doi:10.1056/NEJMoa1608345