Efficacy and Safety of Switching from Adalimumab to Baricitinib: Long-Term Data from Phase 3 Extension Study in Patients with Rheumatoid Arthritis

Michael E Weinblatt¹, Peter C. Taylor², Edward C. Keystone³, Robert A. Ortmann⁴, Maher Issa⁴, Li Xie⁴, Stephanie de Bono⁴ and Yoshiya Tanaka⁵, ¹Brigham and Women’s Hospital, Boston, MA, ²Botnar Research Centre, Univ of Oxford, Oxford, United Kingdom, ³Mount Sinai Hospital, Toronto, ON, Canada, ⁴Eli Lilly and Company, Indianapolis, IN, ⁵University of Occupational and Environmental Health, Kitakyushu, Japan

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Janus kinase (JAK) and rheumatoid arthritis (RA)

Session Information

Date: Sunday, October 21, 2018

Title: 3S087 ACR Abstract: RA–Treatments I: JAK Inhibitors (886–891)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Baricitinib (bari) is an oral JAK1/JAK2 inhibitor approved for the treatment of moderately to severely active RA in adults in over 40 countries, including European countries, the United States, and Japan. In the 52-week Phase 3 RA-BEAM study, bari 4-mg once daily (QD) showed clinical improvements compared with placebo (PBO) and with adalimumab (ADA) in MTX-inadequate-responder (IR) patients (pts).¹ The objective of this analysis was to evaluate efficacy, patient-reported outcomes (PRO), and safety in pts from RA-BEAM who switched treatment from ADA to bari after entering a long-term extension (LTE) study (RA-BEYOND).

Methods: In RA-BEAM (completed September 2015), 1305 pts were randomized 3:3:2 to PBO, bari 4-mg QD, or ADA 40-mg every 2 weeks (wks). At wk 52, pts could enter the LTE, where all pts received open-label bari 4-mg but remained blinded to randomized treatment in RA-BEAM. No ADA washout period was applied. Efficacy, PROs, and safety were evaluated in pts who were not rescued in RA-BEAM and entered the LTE ≥48 wks before the data cutoff of April 1, 2017.

Results: Among pts who completed RA-BEAM without rescue, 381/394 (97%) bari (continued bari), and 238/241 (99%) ADA (switched to bari) pts entered the LTE ≥48 wks before the cutoff date and were included in the analysis. Pts who switched from ADA to bari showed improvements in disease control through 24 wks post-switch in the LTE without evidence of worsening through the following 24 wks (Table 1) and showed further small improvements in PRO assessment of pain and physical function (HAQ-DI) through wk 48 (Figure 1). Of pts who were nonresponders (CDAI >10) at the time of switch (107 and 74 in bari and ADA groups, respectively) approximately half reached low disease activity (CDAI ≤10) by wk 48 (54% and 50%, respectively). Exposure-adjusted incidence rates for treatment-emergent adverse events (TEAEs) and infections, including serious AEs, were similar for pts who switched from ADA to bari and those who continued bari (Table 2).

Conclusion: Switching from ADA to bari without ADA washout was associated with maintenance of disease control through 48 wks post-switch, with some nonresponders being able to achieve LDA as well. There was no increase in TEAEs or serious AEs or infections.

Reference: ¹ Taylor PC et al. NEJM, 2017;376:652-62

Table 1. Percent of patients who reached low disease activity and remission at weeks 24 and 48 after entering the LTE RA-BEYOND study for patients switched to baricitinib
	Baricitinib to Baricitinib			Adalimumab to Baricitinib
	Week 0	Week 24	Week 48	Week 0	Week 24		Week 48
CDAI
≤10	273 (71.8)	292 (76.8)	297 (78.2)	164 (68.9)		176 (73.9)		175 (73.5)
≤2.8	104 (27.4)	117 (30.8)	120 (31.6)	58 (24.4)		72 (30.3)		67 (28.2)
SDAI
≤11	273 (71.8)	296 (77.9)	300 (78.9)	164 (68.9)		181 (76.1)		172 (72.3)
≤3.3	108 (28.4)	125 (32.9)	127 (33.4)	59 (24.8)		73 (30.7)		68 (28.6)
DAS28-ESR
≤3.2	188 (49.5)	181 (47.6)	203 (53.4)	120 (50.4)		138 (58.0)		120 (50.4)
<2.6	111 (29.2)	102 (26.8)	128 (33.7)	71 (29.8)		80 (33.6)		71 (29.8)
CDAI, Clinical Disease Activity Index; DAS28-ESR, Disease Activity Score 28-joint count erythrocyte sedimentation rate; LTE, long-term extension; SDAI, Simple Disease Activity Index. Baricitinib to Baricitinib = Patients completing RA-BEAM (Week 52) on baricitinib who continued baricitinib in RA-BEYOND. Adalimumab to Baricitinib = Patients completing RA-BEAM on adalimumab who transitioned to baricitinib (week 52) upon entering the LTE. Week 0 = Baseline of LTE. Data are n (%) using non-responder imputation for missing data

Table 2. Safety through 48 weeks after switch to baricitinib upon entry to RA-BEYOND
	Baricitinib to Baricitinib (n = 381; PYE = 262.0)	Adalimumab to Baricitinib (n = 238; PYE = 224.0)
Patients with ≥1 TEAE	211 (55.4) [80.5]	162 (68.1) [72.3]
Infections	104 (27.3) [39.7]	87 (36.6) [38.8]
Herpes zoster	6 (1.6) [2.3]	5 (2.1) [2.2]
Gastrointestinal disorders	41 (10.8) [15.6]	29 (12.2) [12.9]
AEs that led to permanent study drug discontinuation	7 (1.8) [2.7]	6 (2.5) [2.7]
Patients with ≥1 SAE	32 (8.4) [12.2]	18 (7.6) [8.0]
Serious infections	10 (2.6) [3.8]	5 (2.1) [2.2]
AE, adverse event; EAIR, exposure-adjusted incidence rate; PYE, patient-years of exposure; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Data are n (%) [EAIR].

Disclosure: M. E. Weinblatt, Amgen, BMS, Crescendo Bioscience, Sanofi/Regeneron, 2,Abbvie, Amgen, BMS, Crescendo Bioscience, Corrono, GSK, Gilead, Eli Lilly and Company, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Set Point, UCB, 5,Lycero, Can-fite, Scipher, Vorso, Inmedix, 1; P. C. Taylor, Celgene, Eli Lilly and Company, Galapagos, UCB, 2,AbbVie, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Pfizer, UCB, Biogen, Sandoz, Novartis, Janssen, 5; E. C. Keystone, AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Eli Lilly and Company, Pfizer Pharmaceuticals, Sanofi-Aventis, 2,AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Eli Lilly and Company, Merck, Pfizer Pharmaceuticals, Sandoz, UCB, 5, 9,Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, 8; R. A. Ortmann, Eli Lilly and Company, 1, 3; M. Issa, Eli Lilly and Company, 1, 3; L. Xie, Eli Lilly and Company, 1, 3; S. de Bono, Eli Lilly and Company, 1, 3; Y. Tanaka, Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama, 2,Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, Pfizer, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi-kasei, 5.

To cite this abstract in AMA style:

Weinblatt ME, Taylor PC, Keystone EC, Ortmann RA, Issa M, Xie L, de Bono S, Tanaka Y. Efficacy and Safety of Switching from Adalimumab to Baricitinib: Long-Term Data from Phase 3 Extension Study in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-switching-from-adalimumab-to-baricitinib-long-term-data-from-phase-3-extension-study-in-patients-with-rheumatoid-arthritis/. Accessed .

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