Data from a Phase IIb study presented today at EULAR 2012, the Annual Congress of the European League Against Rheumatism, show that 76% of patients with active rheumatoid arthritis (RA) receiving either 4mg or 8mg of baricitinib, an oral JAK1/JAK2 inhibitor, plus stable methotrexate (MTX) achieved ACR20* response compared with 41% of placebo-treated patients (p≤0.001) at 12 weeks. The 4mg and 8mg doses of baricitinib demonstrated statistical superiority to placebo in all clinical outcomes measured, including ACR20/50/70*, DAS28**-CRP and DAS28-CRP <2.6. Adverse events (AEs) were mild and no new safety signals were reported, according to the study authors.
Results of the 12-week primary endpoint analysis conducted in 301 patients with moderate to severe RA and inadequate responses to MTX demonstrate that 35% and 23% of patients taking the 4mg achieved ACR50/70 responses respectively; 40% and 20% of patients taking the 8mg dose achieved ACR50/70, compared to 10% and 2% in the placebo groups respectively. Greater proportions of patients achieved disease remission as judged by the DAS28-CRP <2.6 in the 4mg (37%) and 8mg (22%) dose groups compared to placebo (4%) (p≤0.001). Furthermore, of patients receiving the 4mg or 8mg doses, 60% and 67% respectively achieved the minimum clinically important difference (MCID***) for the HAQ-DI**** compared to placebo (41%) at week 12.
"The JAK1/JAK2 signalling pathway has been shown to be important in the pathobiology of RA and no other JAK1/JAK2 inhibitor treatments have yet been approved for the treatment of RA," said Dr Edward Keystone, University of Toronto, Canada and lead author of the study. "There is still a large proportion of patients that have inadequate responses to currently approved treatments for RA and baricitinib could represent a new, viable treatment option for this group of patients. The results of this study would suggest that the compound appears worthy of future Phase III investigation."
According to the researchers, onset of efficacy was rapid for ACR20, ACR50, ACR70, and DAS28-CRP, with statistically significant differences seen after two weeks of therapy. Dose dependent decreases in hemoglobin, small increases in serum creatinine, and increases in low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were seen. Patients were randomized to receive either placebo or one of four once-daily doses (1, 2, 4, or 8mg) for 12 weeks. The study population was 83% female, with a mean age of 51 years and a mean duration of RA of five to seven years.
Whilst the majority of AEs reported were mild, there were seven serious AE's reported in six patients (two events in the placebo group, four in the 2mg group, one in the 8 mg group). No deaths or opportunistic infections occurred in the active treatment groups. One patient in the placebo group was diagnosed with an opportunistic infection of toxocariasis. A similar rate of infection was observed in the placebo group (12%) and the combined treatment groups (14%), representing the most common treatment emergent AE.
More information: Abstract Number: LB0005
*ACR (American College of Rheumatology) criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate), patient assessment, physician assessment, pain scale and disability/functional questionnaire. ACR20 refers to a 20% improvement in tender/swollen joint counts, as well as three of the five other criteria. ACR50 refers to a 50% improvement and ACR70 refers to a 70% improvement.
**DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual's RA is. It assesses number of tender and swollen joints (out of a total of 28), levels of C-reactive protein (CRP, a protein found in the blood, the levels of which rise in response to inflammation), and the patient's 'global assessment of global health'. A higher score indicates more active disease. A score of <2.6 indicates that the patient is in remission.
***MCID (Minimum clinically important difference) represents the smallest improvement in disease considered worthwhile by a patient.
****HAQ DI (Health Assessment Questionnaire Disease Index) is a patient questionnaire that measures function and health-related quality of life through measuring a patient's ability to perform everyday tasks.