Background/Purpose: Baricitinib (bari) is an oral,
reversible inhibitor of Janus kinase (JAK)1/JAK2 being developed as QD
treatment for patients (pts) with RA. In phase (ph) 1 studies, transient
increases in total lymphocyte count were seen within hours of dosing and
returned to baseline prior to the next daily dose;¹ ph 3 data were
consistent with these observations.^2,3 The objective of this
analysis was to examine changes over time in lymphocyte subsets in RA pts
treated with bari or placebo (PBO) in ph 3 RA-BUILD and RA-BEACON studies.

Methods: Pts had active RA with insufficient response
(IR) to conventional synthetic DMARDs (csDMARDs) (RA-BUILD; N=684) or TNF
inhibitors (TNFi) (RA-BEACON; N=527). Pts were randomized 1:1:1 to receive PBO or
2 or 4mg bari QD for 24 weeks (wks). Lymphocyte subsets and natural killer (NK)
cells were quantified by flow cytometry at baseline and Wks 4, 12, and 24.
Total lymphocyte count was measured at all study visits. Change from baseline
and differences vs PBO were evaluated. At Wks 12 and 24, phlebotomy was
conducted before administering study drug (reflecting trough concentration).

Results: Compared to PBO, significant improvements in
disease activity were seen for bari in both studies^2,3. Total
lymphocyte increases seen at Wk 4 for bari were generally within normal ranges.
Compared to PBO, change in total lymphocyte count was similar at Wks 12 and 24,
respectively, for the bari groups. Increased T cells, B cells, and NK cells
were seen at Wk 4, while decreased T cells and NK cells and increased B cells
were seen at Wks 12 and 24 for the bari groups (Table 1). These changes were
generally within normal ranges. Changes in other T- and B-cell populations were
somewhat variable, but generally reflected these patterns (Table 1). Decreased
NK cell count did not appear to be associated with an increased incidence of
infection (Table 2).

Conclusion: In ph 3 studies, QD oral bari produced
significant clinical improvements in disease activity in csDMARD-IR and TNFi-IR
RA patients. These improvements were accompanied by a variety of changes in
lymphocyte counts, predominantly within normal ranges, including transient
increases from baseline in total lymphocyte count, transient increases followed
by decreases from baseline in T cells and NK cells, and sustained
increases from baseline in B cells. Similar lymphocyte subset and NK cell
assessments will be available in a long-term extension study that receives pts
from the bari ph 3 RA program.

1.      
Shi JG, et al. J
Clin Pharmacol. 2014;54:1354-61

2.      
Dougados M et al.
Ann Rheum Dis. 2015;74:Suppl(2)79

3.       Genovese M, et al. Ann Rheum Dis
2015;74:Suppl(2)75