Background/Purpose: Baricitinib (formerly, LY3009104/INCB028050) is a novel, oral inhibitor of the JAK1 and JAK2 in the JAK-STAT pathway known to be of importance in the pathobiology of rheumatoid arthritis (RA) and has previously been shown to improve the signs and symptoms of RA after 12 weeks of treatment.¹ This study evaluates the patient-reported outcomes (PROs) within a 24-week blinded phase 2b study for 1 mg, 2 mg, 4 mg, and 8 mg baricitinib once daily (QD) at 12 weeks, and 4 mg and 8 mg at 24 weeks.

Methods: Patients with active RA and on stable doses of methotrexate were randomized (2:1:1:1:1) to receive either placebo (PBO) or 1 of 4 QD baricitinib doses (1, 2, 4, or 8 mg) for 12 weeks. Patients assigned to placebo or 1 mg were reassigned to an exploratory 4 mg QD or 2 mg BID group between weeks 12 and 24 and were excluded from the primary 24-week analysis; patients initially assigned to 2 mg, 4 mg, or 8 mg remained on the same treatment. PROs included patient global assessment (PtGA) of disease activity (Visual Analog Scale [VAS]), pain (VAS), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), health-related quality of life (Medical Outcomes Study [MOS] Short Form 36 [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and duration of morning stiffness. Analyses were done using analysis of covariance (ANCOVA). Statistical comparisons of means were conducted for each active treatment group against the PBO group; p-values were not adjusted to correct for multiple comparisons.

Results: Of 301 randomized patients, those who received baricitinib experienced clinically meaningful improvements in most PROs as early as week 2 vs. PBO as well as at 12 weeks (Table 1). These improvements were maintained or continued to improve through 24 weeks (e.g., change from baseline for 4 and 8 mg groups, respectively, FACIT-F: 5.32 [SEM: 1.31], 5.00 [SEM: 1.52]; SF-36 PCS: 7.32 [SEM: 0.97], 7.67 [SEM: 1.23]).

Table 1. Patient-Reported Outcomes at 12 Weeks Showing Mean Change From Baseline (LOCF), (Mean [SEM])

Measure	PBO (N=98)	1 mg (N=49)	2 mg (N=52)	4 mg (N=52)	8 mg (N=50)
PtGA (VAS)	-10.3	-24.9*** (3.89)	-16.2 (3.11)	-25.4*** (3.03)	-29.8*** (3.00)
Pain (VAS)	-8.8	-22.8*** (3.91)	-14.2 (2.47)	-25.0*** (2.69)	-25.3*** (2.87)
Physical function (HAQ-DI)	-0.10	-0.35** (0.08)	-0.18 (0.07)	-0.33*** (0.06)	-0.39*** (0.07)
SF-36 Mental Component Score	0.88	2.54 (1.73)	1.89 (0.96)	2.39 (1.11)	3.03 (1.51)
SF-36 Physical Component Score	3.22	6.66* (1.17)	4.15 (1.08)	7.07*** (1.03)	7.00* (1.28)
Fatigue (FACIT-F)	2.02	4.48 (1.51)	3.80 (1.28)	4.41* (1.21)	4.11 (1.41)
Morning Stiffness Duration (minutes)	-33.9	-49.5* (10.51)	-30.7 (6.64)	-75.0*** (20.09)	-62.7*** (12.48)

* p≤0.05, ** p≤0.01, ***p≤0.001

Conclusion: In this phase 2b study in patients with RA, those who received baricitinib reported clinically meaningful improvements as early as week 2 in most PROs relative to PBO as well as at 12 weeks. These improvements were maintained or continued to improve through 24 weeks.

1. Keystone EC, et al. Ann Rheum Dis. 2012;71(Suppl 3):152.

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