Safety and Efficacy of Baricitinib in Elderly Patients with Moderate to Severe Rheumatoid Arthritis

Roy Fleischmann¹, Jahangir Alam², Vipin Arora², John D. Bradley², Douglas E. Schlichting² and David Muram², ¹Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, ²Eli Lilly and Company, Indianapolis, IN

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: rheumatic disease and rheumatoid arthritis (RA), Rheumatology

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Baricitinib (bari), an oral JAK1 and JAK2 inhibitor, is in development for patients (pts) with moderate to severe RA. Drug-related problems are common in the elderly; therapies may be less effective and adverse effects more common. The purpose of this post hoc analysis was to evaluate the safety and efficacy of bari in the elderly subpopulation of 2 pooled phase 3 studies.

Methods: Patients with ≥6 swollen and tender joints and no prior biologic DMARD use were eligible for study inclusion. In the RA-BUILD study, csDMARD-IR pts with hsCRP ≥3.6 mg/L were randomized to placebo (PBO) or bari (2 or 4 mg) once daily (QD).¹ In RA-BEAM, methotrexate (MTX)-IR pts with X-ray erosions and hsCRP ≥6.0 mg/L were randomized to PBO QD, bari 4 mg QD, or adalimumab (ADA) 40 mg biweekly.² Patients continued background csDMARD (including MTX) therapy. The primary endpoint in both trials was ACR20 at Week (Wk) 12 for bari 4 mg vs. PBO. This post hoc analysis combined data from both trials providing overall samples for PBO (N=716) and bari 4 mg (N=714). Elderly pts were defined as those ≥65 years of age. Summary statistics are presented for demographic, efficacy, and safety data for pts aged <65 and ≥65 years.

Results: In these 2 studies, 249 patients ≥65 years old were randomized and initially treated with PBO (n=113) and bari 4 mg (n=136) (Table 1). The primary endpoints were met for both studies; bari showed significant differences vs. PBO for ACR20 at Wk 12; all key secondary endpoints were also met including mean change in DAS28, SDAI, and HAQ-DI.^1,2 Efficacy measures were similarly improved in pts <65 and ≥65 years of age (Table 1). Adverse events (AEs) occurred more frequently in the elderly population compared to pts aged <65 years; however, the prevalence of serious adverse events (SAEs) and discontinuations due to AEs was not different from PBO (Table 2). At 12 wks there were 2 deaths (both in PBO group <65) and cardiac events were rare, as were serious infections (Table 2); there were 2 herpes zoster events (both in bari 4 mg ≥65). There was 1 SAE of hospitalization due to thrombophlebitis (bari 4 mg <65) and 3 due to fractures, all related to falls (PBO <65, n=1; bari 4 mg <65, n=1; bari 4 mg ≥65, n=1); none of these pts discontinued the study and all events resolved.

Conclusion: In 2 phase 3 studies of bari in RA pts, age did not affect efficacy, but as expected there were more AEs in the elderly in both treatment arms. References: ¹Dougados M et al. Ann Rheum Dis 2015;74(S2):79. ²Taylor PC et al. Arthritis Rheumatol 2015;67(S10):3927-3928.

Table 1. Selected Efficacy Outcomes at Week 12
	PBO		Bari 4 mg QD
	<65 years (N=603)	≥65 Years (N=113)	<65 years (N=578)	≥65 Years (N=136)
ACR20, n (%)	237 (39.3)	49 (43.4)	387 (67.0)	92 (67.6)
∆HAQ-DI	-0.3 (0.03)	-0.3 (0.08)	-0.6 (0.03)	-0.6 (0.07)
∆DAS28-hsCRP	-1.0 (0.06)	-1.2 (0.17)	-2.1 (0.06)	-2.4 (0.17)
∆SDAI	-13.4 (0.67)	-15.1 (1.79)	-22.7 (0.69)	-25.6 (1.69)
ACR20=American College of Rheumatology 20% improvement criteria; Bari=baricitinib; DAS28=Disease Activity Score 28 joints; hsCRP=high sensitivity C-reactive protein; HAQ-DI=Health Assessment Questionnaire – Disability Index; LSM=least square means; mLOCF=modified last observation carried forward; NRI=nonresponder imputation; PBO=placebo; SE=standard error; SDAI=Simple Disease Activity Index; SE=standard error; ∆=change from baseline
Data presented as NRI, n (%) or mLOCF, LSM (SE) change from baseline.

Table 2. Safety Outcomes at Week 12
	PBO		Bari 4 mg QD
	<65 years (N=603)	≥65 Years (N=113)	<65 years (N=578)	≥65 Years (N=136)
Patients with ≥1 adverse event	524 (86.9)	109 (96.5)	503 (87.0)	133 (97.8)
Discontinuation from study due to adverse event or death	15 (2.5)	6 (5.3)	13 (2.2)	7 (5.1)
Serious adverse event	15 (2.5)	7 (6.2)	10 (1.7)	6 (4.4)
Serious infections	6 (1.0)	2 (1.8)	3 (0.5)	3 (2.2)
Cardiac disorders*	2 (0.3)	1 (0.9)	1 (0.2)	0
Data presented as n (%). *Any serious adverse event based on the MedDRA dictionary system organ class; Bari=baricitinib; PBO=placebo

Disclosure: R. Fleischmann, AbbVie, Amgen, Astra Zeneca , Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Roche, Sanofi-Aventis, Pfizer,UCB, 5; J. Alam, Eli Lilly and Company, 1,Eli Lilly and Company, 3; V. Arora, Eli Lilly and Company, 1,Eli Lilly and Company, 3; J. D. Bradley, Eli Lilly and Company, 1,Eli Lilly and Company, 3; D. E. Schlichting, Eli Lilly and Company, 1,Eli Lilly and Company, 3; D. Muram, Eli Lilly and Company, 1,Eli Lilly and Company, 3.

To cite this abstract in AMA style:

Fleischmann R, Alam J, Arora V, Bradley JD, Schlichting DE, Muram D. Safety and Efficacy of Baricitinib in Elderly Patients with Moderate to Severe Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/safety-and-efficacy-of-baricitinib-in-elderly-patients-with-moderate-to-severe-rheumatoid-arthritis/. Accessed .

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