ANALYSIS OF HEMATOLOGICAL CHANGES IN TOFACITINIB-TREATED PATIENTS WITH ULCERATIVE COLITIS ACROSS PHASE 3 INDUCTION AND MAINTENANCE STUDIES

Background: Tofacitinib is an oral, small molecule JAK inhibitor approved in several countries, including the US, for the treatment of ulcerative colitis. Changes in hematological parameters in participants of OCTAVE Induction 1 & 2 (NCT01465763 & NCT01458951) and OCTAVE Sustain (NCT01458574)1 were evaluated. Methods: In OCTAVE Induction 1 & 2, patients (pts) received either placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomized into OCTAVE Sustain for 52 weeks (received placebo, tofacitinib 5 or 10 mg BID). Mean absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PC), and hemoglobin (Hgb) level changes were analyzed. Hematological adverse events were evaluated. Results: Following 8 weeks of treatment (placebo or tofacitinib 10 mg BID) in OCTAVE Induction 1 & 2, Hgb levels, ALC, and ANC were stable, while PC declined from baseline (Table). Up to Week 52 of OCTAVE Sustain, Hgb levels increased and ALC, ANC, and PC declined in all groups (Table). During OCTAVE Induction 1 & 2, adverse events of anemia were reported in 22 (2.4%) tofacitinib-treated pts compared with 9 (3.8%) placebo-treated pts. During OCTAVE Sustain, the incidence rates (IRs; unique pts with events per 100 pt-years) of anemia were 2.91, 5.51, and 2.55 for placebo, tofacitinib 5 and 10 mg BID, respectively. No adverse events of neutropenia were reported during OCTAVE Induction 1 & 2. In OCTAVE Sustain, IRs were 0.00, 0.67, and 0.64 for placebo, tofacitinib 5 and 10 mg BID, respectively. During OCTAVE Induction 1 & 2, two (0.2%) tofacitinib-treated pts had adverse events of lymphopenia, and no adverse events of lymphopenia occurred during OCTAVE Sustain. Discontinuations due to laboratory abnormalities were low. Two (0.2%) tofacitinib-treated pts discontinued in OCTAVE Induction 1 & 2 due to ALC decline (two sequential readings <0.5 × 109/L), and five (0.6%) tofacitinib-treated pts discontinued due to Hgb decline (two sequential values <0.8 g/dL or >30% decrease from baseline), compared to Hgb decline in one (0.4%) placebo-treated pt. In OCTAVE Sustain, one (0.3%) pt discontinued due to Hgb decline. Conclusion: In OCTAVE Sustain, treatment with both tofacitinib doses resulted in decreased ALC, ANC, and PC, and increases in Hgb levels. There was no dose dependency in anemia or neutropenia IRs. Similar trends were observed in pts with rheumatoid arthritis treated with tofacitinib.2 Increases in Hgb were also found in pts with inflammatory bowel disease and rheumatoid arthritis treated with tumor necrosis factor inhibitors.3-5 References: 1. Sandborn WJ et al. N Engl J Med 2017;376:1723-36. 2. Schulze-Koops H et al. Rheumatology 2017;56:46-57. 3. Koutroubakis IE et al. Inflamm Bowel Dis 2015;21:1587-93. 4. Rubin DT et al. Inflamm Bowel Dis 2012;18:818-25. 5. Doyle MK et al. Semin Arthritis Rheum 2009;39:123-31. [Table presented]