THU0209 Characterization of Changes in Lymphocyte Subsets in Baricitinib-Treated Patients with Rheumatoid Arthritis in A Phase 3 Study (RA-BEAM)

Background Baricitinib (bari; an oral JAK 1/JAK 2 inhibitor) is in development for patients (pts) with active RA. In healthy subjects, absolute lymphocyte counts (ALC) increased after bari administration, returning to baseline (BL) by 24 hrs.1 Objectives To examine changes in ALC and lymphocyte (LYM) subsets in pts with active RA treated with bari (4 mg QD), placebo (PBO), or adalimumab (ADA, 40 mg Q2W). Methods 1305 pts with active RA despite MTX treatment were randomized 3:3:2 to PBO, bari, or ADA. ALC, T, and B cell subsets (T: Th1, Th17, CD4, CD8, T reg, CD3+CD4+CD127-/loCD25+; B: switched/nonswitched memory, mature naive, immature transitional), and natural killer (NK) cells were quantified by flow cytometry at BL and wks 4, 12, and 24. Wk 4 phlebotomy was postdose bari or PBO; wks 12 and 24 were predose. Results ALC and T cells/subsets increased with bari and ADA at wk 4 (generally within normal ranges), returning to near BL at wks 12 and 24 in bari but remaining elevated in ADA (Table). B cells/subsets increased at wks 4 in bari and ADA and remained elevated through wk 24. NK cells were increased at wk 4 in bari and were below BL but within the normal range at wks 12 and 24; NK cells were increased at wks 12 and 24 in ADA. The percentages of pts with ≥1 low NK cell count were 20.5%, 32.6%, and 20.6% in PBO, bari, and ADA, respectively; percentage of pts with ALC CTCAE grade ≥2 were 14.1%, 9.9%, and 10.0%. Through wk 24, serious infection rates were 1.4%, 1.0%, and 0.6% for PBO, bari, and ADA; rates were 1.0%, 1.3%, and 0%, respectively, in pts with ≥1 low NK cell count and 2.9%, 4.2%, and 0% in pts with ≥1 ALC CTCAE Grade ≥2 value. Rates of herpes zoster (HZ) were 0.4%, 1.4%, and 1.2% for PBO, bari, and ADA; rates were 0%, 0.6%, and 0%, respectively, in pts with ≥1 low NK cell count and 1.4%, 2.1%, and 0% in pts with ≥1 ALC CTCAE Grade ≥2 value (no statistically significant differences between treatment groups). Table 1. ALC/LYM subsets at BL, Wks 4, 12, and 24 (Observed Mean Count) PBO (N=488) Bari (N=487) ADA (N=330) BL Wk 4 Wk 12 Wk 24 BL Wk 4 Wk 12 Wk 24 BL Wk 4 Wk 12 Wk 24 ALC, cells/μL 1820 1750 1800 1800 1810 2160*** 1860 1830 1810 2010*** 2180*** 2140*** T cells, cells/μL 1300 1259 1309 1301 1294 1487*** 1314 1286 1314 1426*** 1533*** 1553*** B cells, cells/μL 215 208 215 212 209 316*** 309*** 296*** 211 284*** 303*** 306*** NK cells, cells/μL 214 215 215 211 223 290*** 188*** 191** 211 220 230* 232* *p≤0.05, **p≤0.01, ***p≤0.001 vs PBO. Reference ranges: ALC = 800–4280; T cells = 603–2990; B cells = 107–698; NK cells = 95–640. Conclusions Changes in ALC and subpopulations with bari in RA-BEAM were largely within normal ranges and are consistent with previous data.2 Sustained increases in B cells were observed in bari and ADA. Sustained increases in ALC/T cells were only seen in ADA. A modest reduction in NK cells at wks 12 and 24 with bari was not associated with serious infection or HZ. References Shi JG, et al. J Clin Pharmacol. 2014;54:1354–61 Emery P, et al. Arthritis Rheumatol. 2015;67 (suppl 10) Disclosure of Interest Y. Tanaka Grant/research support from: Mistubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, R. Fleischmann Grant/research support from: Pfizer, Inc, Eli Lilly and Company, Consultant for: Eli Lilly and Company, Pfizer, M. Schiff Grant/research support from: Eli Lilly and Company, Consultant for: Eli Lilly and Company, T. Takeuchi Grant/research support from: Chugai Pharmaceutical Co., Ltd, Eli Lilly and Company, Consultant for: Eli Lilly and Company, E. Keystone Grant/research support from: Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Company, F. Hoffmann-La Roche Inc, Janssen Inc, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB. , Consultant for: Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Eli Lilly and Company, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Merck, Pfizer Pharmaceuticals, UCB, Speakers bureau: Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, UCB, Amgen, M. Weinblatt Grant/research support from: Crescendo Bioscience, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, Crescendo Bioscience, S. Zuckerman Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Issa Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Thanabalasundrum Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, B. Augendre-Ferrante Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, D. Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P. Taylor Grant/research support from: Eli Lilly and Company, UCB, Consultant for: UCB, Eli Lilly and Company, Pfizer, Galapagos, Merck, GlaxoSmithKline, AbbVie, Takeda, Bristol-Myers Squibb