Persistence of treatment in patients with ulcerative colitis who responded to tofacitinib therapy: data from the open-label, long-term extension study, OCTAVE open

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Aim:This post hoc analysis evaluated tofacitinib persistence in patients with UC in OCTAVE Open, an open-label, long-term extension study of patients receiving tofacitinib 5 or 10 mg twice daily. Methods: Kaplan-Meier estimates for tofacitinib drug survival and reasons for discontinuations were evaluated. Baseline factors were analysed as predictors of persistence. Results:This analysis included 603 patients: 280 entered OCTAVE Open with a clinical response (164 in remission and 116 not in remission), 220 were delayed responders, 75 were retreatment responders and 35 were dose escalation responders, treated for up to 7 years in OCTAVE Open. Of these, 118 (42.1%) responders, 121 (55.0%) delayed responders, 40 (53.3%) retreatment responders and 17 (48.6%) dose escalation responders discontinued tofacitinib with a median time to discontinuation of 5.6, 4.5, 4.0 and 4.4 years, respectively. The estimated 2- and 5-year drug survival rates in the responders (including patients in remission and not in remission) were 73.9% and 54.5%, respectively. Corresponding persistence values for delayed responders were 69.5% and 45.2%, for retreatment responders, 70.7% and 40.0%, and for dose escalation responders, 74.3% and 32.8%. ConclusionIn: OCTAVE Open, a high proportion of patients maintained tofacitinib treatment, with the median survival by group ranging from 4.0 to 5.6 years although these analyses are post hoc and limited by sample size. Further research should focus on factors to enhance persistence with tofacitinib treatment in patients with UCThis study was sponsored by Pfizer. Medical writing support, under the guidance of the authors, was provided by Helen Findlow, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461–464

tofacitinib treatment is associated with modest and reversible increases in serum lipids in patients with ulcerative colitis

Background & Aims Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We analyzed inflammation, lipid concentrations, and incidence rates of major adverse cardiovascular (CV) events (MACEs) in patients who received tofacitinib in worldwide studies. Methods We collected data from 1157 patients who participated in 3 8-week induction studies (1 phase-2 study and 2 phase-3 studies; patients received tofacitinib 10 mg twice daily or placebo), a 52-week phase-3 maintenance study of responders (patients received tofacitinib 5 or 10 mg twice daily or placebo), and an ongoing long-term extension study of patients who did and did not respond to induction or maintenance therapy (patients received tofacitinib 5 or 10 mg twice daily). Lipid concentrations were assessed from induction baseline to week 61 (week 52 of maintenance therapy). We calculated MACE incidence rates (patients with ≥1 event per 100 patient-years of exposure) and Reynolds risk score (RRS; a composite score used to determine CV risk) for patients given tofacitinib vs placebo. Results The mean RRS was P Conclusions In an analysis of data from 5 trials of patients with UC who received tofacitinib, we found reversible increases in lipids with treatment and inverse correlations with reduced levels of high-sensitivity C-reactive protein. We did not find clinically meaningful changes in lipid ratios or RRS. MACEs were infrequent and not dose-related. Clinical trial registration Clinicaltrials.gov : A3921063 ( NCT00787202 ); OCTAVE Induction 1 ( NCT01465763 ); OCTAVE Induction 2 ( NCT01458951 ); OCTAVE Sustain ( NCT01458574 ); OCTAVE Open ( NCT01470612

Efficacy and safety of tofacitinib dose de‐escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE Open

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