Characterization of changes in lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis in a phase 3 study (RA-BEAM) (EULAR 2016) - Jun 12, 2016 - Abstract #THU0209; Pres time: Jun 9, 2016; 11:45 AM; Location: Poster area; P3, N=1,301; NCT01710358; Sponsor: Eli Lilly; "Changes in ALC and subpopulations with bari in RA-BEAM were largely within normal ranges...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."
P3 data • Immunology • Rheumatoid Arthritis
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17th Annual Congress of the European League Against Rheumatism, Jun 8-11, 2016, London, UK
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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. ALC/LYM Subsets at BL, Wks 4, 12, and 24 (Observed Mean Count)
BL
Wk 4
Wk 12
Wk 24
BL
Wk 4
Wk 12
Wk 24
BL
Wk 4
Wk 12 Wk 24
PBO (N=488)
Bari (N=487)
ADA (N=330)
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.
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