Background/Purpose: Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Post-baseline (BL) decreases in mean peripheral neutrophil count were observed in Phase (P) 3 trials, although no association between neutropenia and serious infection events (SIEs) was observed.¹ Given the role of neutrophils in initiation and progression of RA,² we further evaluated early post-treatment neutrophil changes to identify any trends with early clinical responses (ER) or SIEs in patients (pts) receiving tofacitinib 5 or 10 mg twice daily (BID).

Methods: Data were pooled from 6 P3 studies. Pts recruited to 4 of these received stable doses of background DMARDs, mainly methotrexate (MTX). Decreases from BL in neutrophil counts were evaluated at Week (W) 4. Quartile categories (Q): 0 to <650 (Q1); 650 to <1410 (Q2); 1410 to <2500 (Q3); ≥2500 (Q4) were defined by quartiles obtained from pts with a mean decrease from BL in neutrophil counts (cells/µL) at W4. ER: decrease from BL in DAS28-4 ESR ≥1.2 at W4. Incidence rates (IRs) for SIEs were compared between categories. Pts receiving tofacitinib (all 6 trials) were included in the analysis presented for tofacitinib 5 and 10 mg BID.

Results: At BL and W4, 1488, 1506, 622 and 179 pts were evaluable for neutrophil counts for tofacitinib 5, 10 mg BID, placebo (PBO), and MTX, respectively. The proportions of pts with any decrease from BL in neutrophil counts were 69%, 73%, 52% and 56% with tofacitinib 5, 10 mg BID, PBO, and MTX, respectively. At W4, pts with neutrophil decreases in the tofacitinib 5 mg BID group were evenly distributed between categories. With tofacitinib 10 mg BID, a higher proportion of pts had neutrophil decreases within Q3 and Q4 than within Q1 and Q2 (Table). Neutrophil decreases with PBO and MTX were mostly within Q1 and Q2 (Table). In general the proportion of pts per category with an ER was slightly higher with tofacitinib 10 vs 5 mg BID. With tofacitinib, a higher proportion of pts with an ER was observed in categories with greater reductions in neutrophil counts (Table). SIEs occurred in 30 and 27 pts in the tofacitinib 5 and 10 mg BID groups, respectively. The distribution of pts with SIEs across categories was variable and there were no consistent trends to indicate an association between SIEs and decreases in neutrophil counts (Table), reflecting studies that did not find associations between SIEs and neutropenia.^3,4

Conclusion: A trend was observed between decreases in neutrophils and ER with tofacitinib. ERs were most commonly seen in pts with the largest category decreases in neutrophil count at W4. No differences were noted between categories with respect to decreases in neutrophil counts and SIEs.

1. He Y et al.  BMC Musculoskelet Disord 2013; 14: 298.

2. Wright HL et al.  Rheumatology (Oxford) 2010; 49: 1618-31.

3. Fleischmann R et al.  N Engl J Med 2012; 367: 495-507.

4. Kremer JM et al.  Arthritis Rheum 2012; 64: 970-81.