Baricitinib Outperforms Adalimumab in PROs in Phase 3 Study

Newly published results of a phase 3 study of baricitinib, a once-daily oral Janus kinase inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA), show that the small-molecule drug provided greater improvements in patient-reported outcomes than either placebo or the biologic adalimumab (Humira).
The Center for Biosimilars Staff
September 05, 2017
Newly published results of a phase 3 study of baricitinib, a once-daily oral Janus kinase inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA), show that the small-molecule drug provided greater improvements in patient-reported outcomes (PROs) than either placebo or adalimumab (Humira). The study, funded by Eli Lilly and Incyte Corporation, is published in Annals of the Rheumatic Diseases.

The randomized, double-blind, double-dummy, placebo-controlled and active-controlled, parallel-arm, 52-week study was conducted at 281 centers in 26 countries. A total of 1307 patients were randomized to receive placebo (n = 488), baricitinib at a daily dose of 4 mg (n = 487), or subcutaneously administered adalimumab at a biweekly dose of 40 mg (n = 330) together with existing background therapy, including methotrexate. With primary analysis marked for week 12, patients receiving placebo switched to baricitinib in week 24.

PROs were prespecified as secondary objectives in the study, and included:
  • The Health Assessment Questionnaire-Disability Index
  • The Patient’s Global Assessment of Disease Activity
  • Patients’ assessment of visual pain analogue scales
  • The Functional Assessment of Chronic Illness Therapy-Fatigue scale
A 3- to 4-point change was considered a minimum clinically important difference (MCID). PROs including duration of morning joint stiffness and morning joint stiffness severity, worst tiredness, and worst joint pain numeric rating scales were recorded using a daily electronic diary from day 1 to week 12.

Health-related quality of life was assessed using Medical Outcomes Study Short-Form-36, which assesses 8 domains. The EuroQoL 5-Dimensions Health State Profile was also used, and included a descriptive system of the respondent’s health and a rating of their current health state. The Work Productivity and Activity Impairment Questionnaire-RA was used to measure overall work productivity and impairment of regular activities.

The researchers found the following:
  • At week 12, 58% of patients in the placebo group met or exceeded the MCID for the Health Assessment Questionnaire-Disability Index, compared with 75% in the baricitinib group, and 71% in the adalimumab group; at week 52, the percentages were 68% for the baricitinib group and 58% for adalimumab group.
  • At day 1, morning stiffness for each group lasted a median time of 60 minutes. The severity of morning joint stiffness (on a scale of 0 to 10 with 10 being the worst) was 5.4, 5.5, and 5.3 for the baricitinib, placebo, and adalimumab groups, respectively. Worst tiredness, also on a 0 to 10 scale, was 5.6, 5.6, and 5.5, and worst joint pain was 5.9, 5.9, and 5.7, respectively. By week 12, baricitinib treatment, compared with placebo and adalimumab, improved the duration of morning joint stiffness (27.1, 60.0, and 36.6, respectively), severity of morning joint stiffness (3.0, 4.1, and 3.5), tiredness (3.6, 4.3, and 3.9), and joint pain (3.4, 4.6, and 4.0).
  • In the Functional Assessment of Chronic Illness Therapy-Fatigue, 66% of patients in the baricitinib group met or exceeded the MCID at week 12, compared with 59% in the placebo group, and 68% in the adalimumab group. At week 52, the values were 60% for the baricitinib group and 54% for the adalimumab group.
  • In the health-related quality of life assessment, compared with adalimumab, patients treated with baricitinib showed statistically significant improvement in most of the domains at week 52, except for the domain measuring mental health.
  • In the The EuroQoL 5-Dimensions Health State Profile, the least square mean change from baseline at 12 weeks was 0.184 for the baricitinib arm, 0.102 for the placebo arm, and 0.167 for the adalimumab arm. At 52 weeks, it was 0.154 for the baricitinib arm and 0.129 for the adalimumab arm.
  • No statistically significant improvement in daily activity or work productivity were observed between the baricitinib and adalimumab groups at week 52.
The researchers concluded that patients with RA who were treated with baricitinib experienced greater improvement in most PROs across a variety of domains, compared with patients treated with placebo or adalimumab.

Eli Lilly, sponsor of baricitinib, received a complete response letter from the FDA in April 2017, when the regulatory agency indicated that additional data were necessary in to assess drug safety. Last week, Eli Lilly and the Incyte Corporation announced that they will resubmit their New Drug Application for the drug by the end of January 2018. If approved, baricitinib could exert further pressure on Humira, which already stands to lose RA market share to adalimumab biosimilars, 2 of which are now approved by the FDA.

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