Summary Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open‐label, long‐term extension study. Aims The primary objective of OCTAVE Open was to assess the safety and tolerability of long‐term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. Methods Eligible patients included OCTAVE Induction 1&2 non‐responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient‐years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). Results In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient‐years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09‐0.54); serious infections, 1.61 (1.14‐2.20); herpes zoster (non‐serious and serious), 3.16 (2.47‐3.97); opportunistic infections, 0.87 (0.54‐1.33); major adverse cardiovascular events, 0.16 (0.04‐0.42); malignancies (excluding non‐melanoma skin cancer), 1.03 (0.67‐1.52); non‐melanoma skin cancer, 0.75 (0.45‐1.19); deep vein thrombosis, 0.04 (0.00‐0.23); pulmonary embolism, 0.21 (0.07‐0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. Conclusion Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long‐term efficacy beyond the 52‐week maintenance study.
Summary Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Aim To report incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the tofacitinib UC programme. Methods DVT and PE were evaluated from one phase 2 and two phase 3 induction studies, one phase 3 maintenance study and an ongoing, open‐label, long‐term extension (OLE) study (September 2018 datacut). Data were analysed in induction, maintenance and overall (patients receiving ≥ 1 dose of tofacitinib 5 or 10 mg b.d. in any phase 2, 3 or OLE study) cohorts. Results 1157 patients (2404 patient‐years’ exposure; ≤ 6.1 years’ tofacitinib treatment) were evaluated in the overall cohort. In induction, one placebo‐treated patient had DVT and one had PE; no tofacitinib‐treated patients had DVT/PE. In maintenance, one placebo‐treated patient had DVT and one had PE; no tofacitinib‐treated patients had DVT/PE. In the overall cohort, one patient had DVT (incidence rate [patients with events/100 patient‐years; 95% CI]: 0.04 [0.00‐0.23]); four had PE (0.16 [0.04‐0.41]); all received predominant dose tofacitinib 10 mg b.d.; all had venous thromboembolism risk factors alongside UC. Conclusions In this post hoc analysis of patients with UC, during tofacitinib exposure, one patient had DVT and four had PE, all during the OLE study, on predominant dose 10 mg b.d. (83% of overall cohort patients received predominant dose 10 mg b.d.) with venous thromboembolism risk factors. This analysis is limited by small sample size and limited drug exposure; further studies are needed. ClinicalTrials.gov: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
Background and Aims Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomized, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy. Methods Patients had received tofacitinib 10 mg BID for ≥2 consecutive years and been in stable remission for ≥6 months before enrollment. The primary endpoint was modified Mayo score remission at month 6. Safety was assessed up to February 20, 2020 [data cut-off]. Results 140 patients were randomized [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at month 6 [adjusted difference 12.9%; 95% CI 0.5–25.0]. Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; –3.0–22.6 and 21.1%; –6.1–48.2, respectively], and in patients without versus with prior tumor necrosis factor inhibitor [TNFi] failure [9.5%; –6.6–25.6 and 17.4%; –1.6–36.3, respectively]. AE and serious AE rates were similar across treatment groups; no deaths were reported. Conclusions Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6-months; a longer duration of follow-up during RIVETING will further characterize the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.
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