Eli Lilly and Incyte have announced 52-week efficacy and safety data from the open-label, long-term extension of the Phase 2b JADA study of Baricitinib in patients with active rheumatoid arthritis.
Baricitinib is an orally available Janus kinase ( JAK ) inhibitor being studied for use in the treatment of certain autoimmune conditions, including rheumatoid arthritis.
There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. These enzymes are critical components of signaling mechanisms used by a number of cytokines and growth factors, including several that are elevated in patients with rheumatoid arthritis. Cytokines such as interleukin-6, -12 and -23 and both type 1 and type 2 interferons signal through these pathways. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions.
The long-term extension of the JADA study evaluated the efficacy and safety of Baricitinib in 201 patients taking either 4 mg ( n=108 ) or 8 mg ( n=93 ) once daily for up to 52 weeks. Doses could be escalated to 8 mg once daily at 28 or 32 weeks at the investigator's discretion when the patient presented more than six tender and swollen joints.
As previously reported, in the initial 12-week portion of this study, Baricitinib was associated with statistically significant improvements in the signs and symptoms of rheumatoid arthritis versus placebo, and these responses were maintained or improved during an additional 12 weeks of blinded treatment.
In the long-term extension, the clinical improvements observed at week 24 were sustained through 52 weeks in rheumatoid arthritis patients.
Safety signals observed during the open-label extension were consistent with previously reported results of Baricitinib. Among patients who remained on the 4 mg dose, treatment-emergent adverse events ( TEAEs ) occurred in 57 ( 53% ); serious adverse events ( SAEs ) in 11 ( 10% ); infections in 34 ( 31% ); and serious infections in four ( 4% ).
Among patients who received the 8 mg dose, TEAEs occurred in 59 (63 percent); SAEs in eight (9 percent); infections in 37 (40 percent); and serious infections in two ( 2% ). No opportunistic infections or tuberculosis cases were observed. There was one death in the 8 mg group due to a suspected myocardial infarction.
According to researchers, in this clinical trial Baricitinib showed statistically and clinically significant improvements in the features of this condition, which were maintained throughout a year of treatment. To date, Baricitinib has demonstrated an acceptable safety profile and side effects have generally been straightforward to manage.
This randomized, open-label, long-term extension of Phase 2b JADA study included 201 ( 95% ) of the eligible 212 patients. Of the 201 patients, 184 completed 52 weeks of treatment, 15 discontinued treatment, and two patients had not yet completed the full 52 weeks of treatment. Patients received either 4 mg or 8 mg once-daily doses of Baricitinib beginning at week 24 through week 52.
In the initial 12-week treatment duration, patients received one of four doses of Baricitinib ( 1 mg, 2 mg, 4 mg or 8 mg ) or placebo, administered once daily. In the 12- to 24-week portion of the study, patients initially randomized to placebo or the 1 mg Baricitinib dose were re-randomized to receive either 4 mg once daily or 2 mg twice daily for an additional 12 weeks; patients initially randomized to the 2 mg, 4 mg and 8 mg doses continued therapy with those doses.
Patients who completed week 24 were eligible to receive either the 4- or 8-mg once daily dose through week 52. The study is ongoing, with all patients who are continuing in the study receiving Baricitinib 4 mg once daily. ( Xagena )
Source: European League Against Rheumatism ( EULAR ) Annual Congress, 2013