Patient-reported outcomes across phase 3 studies of bariciti
Patient-reported outcomes across phase 3 studies of baricitinib demonstrate statistically significant improvements in physical function and quality of life symptoms in patients with rheumatoid arthritis (RA)
Pivotal trials show treatment with baricitinib resulted in significant improvements in pain, fatigue and ability to perform daily activities compared to methotrexate – the current standard of care – and adalimumab (Humira ®)*
INDIANAPOLIS, June 9, 2016 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today announced that in two phase 3 trials patients with rheumatoid arthritis (RA) treated with baricitinib reported significant improvements in quality of life symptoms and other patient-reported outcomes compared to methotrexate or adalimumab (Humira ®). Patients with RA also reported improvement in productivity at work. In these studies, significant improvements in patient-reported measures, including pain, physical function, tiredness and morning joint stiffness, were observed as early as one week after initial treatment with baricitinib . These findings were presented today at the Annual European Congress of Rheumatology (EULAR 2016) in London.
Key findings include:
·In the phase 3 RA-BEGIN trial:
o At 24 weeks, 81 percent of patients receiving baricitinib monotherapy and 79 percent of patients receiving baricitinib plus methotrexate had clinically meaningful improvement in physical function compared with 70 percent among those receiving methotrexate alone (p<0.05). Clinically meaningful improvement was defined as an improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) score of ≥0.22.
o At 52 weeks, 68 percent of patients on baricitinib monotherapy and 72 percent of patients on baricitinib in combination with methotrexate saw clinically meaningful improvements in physical function compared to 57 percent of those treated with methotrexate alone (p<0.05).
oAt 24 and 52 weeks, baricitinib (as monotherapy or in combination with methotrexate ) was also associated with significant improvement in pain, and clinically meaningful improvement in fatigue and the physical health components of the quality of life assessment compared with methotrexate alone.
· In the phase 3 RA-BEAM trial, where all patients received background methotrexate therapy:
o At 12 weeks, 75 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 71 percent of patients on adalimumab (p=0.302). Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22.
oAt 24 weeks, 73 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 64 percent of patients on adalimumab (p<0.05).
oAt 52 weeks, 68 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 58 percent of patients on adalimumab (p<0.01).
o At 52 weeks, baricitinib was also associated with significant improvement in pain, and clinically meaningful improvement in fatigue and the physical health components of quality of life compared with adalimumab .
· An analysis of the phase 3 trials found that in each study, patients taking baricitinib have less impairment in work productivity and daily activities compared to patients taking the comparator.
"Our extensive phase 3 clinical trial program demonstrates that baricitinib could, if approved, offer a potentially significant improvement in the treatment of rheumatoid arthritis," said Terence Rooney, M.D., medical director, rheumatoid arthritis, Lilly Bio-Medicines. "In these studies, baricitinib demonstrated superiority on a variety of efficacy measures compared to the leading biologic, adalimumab , as well as the current oral standard of care, methotrexate . Additionally, patients reported their personal experience with baricitinib , further highlighting its positive impact on patients' daily lives and activities."
Physical function was measured using the patient-reported HAQ-DI questionnaire that assesses the ability of a patient to perform daily activities like dressing, eating, walking, grip, etc. Quality of life assessment was made by using the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute, or SF-36, which is a patient-reported survey that measures overall health quality based on physical and psychological functioning.
RA-BEGIN demonstrated that in RA patients who had limited or no previous treatment with any disease-modifying antirheumatic drugs (DMARDs), baricitinib used as monotherapy or in combination with methotrexate showed statistically significant improvements in the physical quality of life measures, as measured by the SF-36, when compared to methotrexate alone. Reported improvements in patient quality of life symptoms were accompanied by an increase in physical function, and decreased pain and fatigue. All the improvements with baricitinib were statistically significant at week 24 and week 52, compared to methotrexate alone.
The RA-BEGIN study included patients who had limited or no prior treatment with methotrexate , and were naïve to other conventional or biologic DMARDs. Part of a larger phase 3 program of more than 3,000 RA patients at various points in the RA treatment continuum, RA-BEGIN enrolled nearly 600 patients who were randomized to one of the following treatment groups:
· Once-weekly oral methotrexate monotherapy
·4 mg once-daily oral baricitinib monotherapy
· 4 mg once-daily oral baricitinib in combination with once-weekly oral methotrexate .
"Left untreated or uncontrolled, rheumatoid arthritis can dramatically impact patients' quality of life," said Steven Stein, M.D., chief medical officer, Incyte Corporation. "Patients and physicians alike deserve better treatment options beyond today's standard of care. If approved, baricitinib has the potential to become an oral drug option that may improve the clinical symptoms of the disease, as well as patients' ability to perform daily activities at home and at work."
The pivotal phase 3 trial, RA-BEAM, showed that RA patients who had previously responded inadequately to methotrexate and were not treated with any biologic, experienced significant improvement in the physical quality of life measures when taking baricitinib compared to patients treated with adalimumab or placebo. Reported improvements in patient quality of life were accompanied by an increase in physical function, and decreased pain and fatigue. The improvements in physical function, pain and physical quality of life with baricitinib were statistically significant at week 24 and week 52, compared to adalimumab .
RA-BEAM was a 52-week trial of 1,305 patients who had active, moderate-to-severe RA, despite ongoing treatment with methotrexate . Patients were randomized to placebo once-daily (n=488), baricitinib 4 mg once-daily (n=487) or adalimumab 40 mg biweekly (n=330). All patients received background methotrexate . At week 24, patients taking placebo were crossed over to the baricitinib treatment group.
In the baricitinib RA development program, no increases in adverse events leading to study drug discontinuation, malignancies, or serious infections were seen for baricitinib vs. placebo or active comparators during the controlled periods of the program. Herpes zoster was reported more frequently for baricitinib vs. placebo. The incidence rates of malignancy, serious infection and herpes zoster did not increase over time including long-term observations.