Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme

Abstract

Background and Aims Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. Methods Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious] and opportunistic infections [OIs] are reported [censored at time of event]. Results In the Induction Cohort [N=1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10mg twice daily [BID] developed SIs. Maintenance Cohort [N=592] SI IRs [95% CI] were 1.94 [0.23–7.00] for placebo, and 1.35 [0.16–4.87] and 0.64 [0.02–3.54] for tofacitinib 5 and 10mg BID, respectively; HZ IRs were 0.97 [0.02–5.42], 2.05 [0.42–6.00] and 6.64 [3.19–12.22], respectively. In the Overall Cohort [N=1157; 82.9% predominantly received tofacitinib 10mg BID], SI, HZ and non-HZ OI IRs were 1.70 [1.24–2.27], 3.48 [2.79–4.30] and 0.15 [0.04–0.38], respectively. No SIs resulted in death. Conclusions During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 versus 5mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open‐label, long‐term extension study with up to 7.0 years of treatment

“…[20][21][22][23][24] In a recent meta-analysis of the real-world effectiveness and safety of tofacitinib for moderate to severely active UC, which included data from 1162 patients in 17 studies, the herpes zoster IR was reported to be 6.9 (95% CI, 4.5-9.3), 25 which is higher than the herpes zoster 25 Prior failure of biologic therapy is a known risk factor for herpes zoster in patients with UC. 26 In addition, with the exception of a higher IR for herpes zoster, the safety of tofacitinib in OCTAVE Open was similar to that reported for other approved UC therapies, including biologics. 27 The IRs of adverse events of special The safety profile of tofacitinib in OCTAVE Open was consistent with previously published long-term studies of tofacitinib in patients with rheumatoid arthritis, active psoriatic arthritis or moderate to severe chronic plaque psoriasis.…”

“…Of note, however, patients receiving tofacitinib in the real‐world settings described in this meta‐analysis had a higher rate of failure of biologic therapy, with nearly 90% of patients having prior biologic exposure and approximately two‐thirds having prior TNFi and vedolizumab failure, versus almost half of patients in the OCTAVE studies being naïve to biologic therapy 25 . Prior failure of biologic therapy is a known risk factor for herpes zoster in patients with UC 26 . In addition, with the exception of a higher IR for herpes zoster, the safety of tofacitinib in OCTAVE Open was similar to that reported for other approved UC therapies, including biologics 27 .…”

130 Worldwide Post-Marketing Safety Surveillance Experience With Tofacitinib in Ulcerative Colitis

“…10 In the PMS data from patients with UC, the most frequently reported infections were nasopharyngitis and herpes zoster, which is consistent with infection AEs reported in tofacitinib clinical trials. 13 Compared with the general population, patients with inflammatory bowel disease are at increased risk of herpes zoster, 8 and this risk is increased further by treatment with immunosuppressive therapies. 14 Consistent with herpes zoster events reported in tofacitinib clinical trials, 13 the majority of herpes zoster infections in the PMS dataset were categorised as not serious.…”

“…13 Compared with the general population, patients with inflammatory bowel disease are at increased risk of herpes zoster, 8 and this risk is increased further by treatment with immunosuppressive therapies. 14 Consistent with herpes zoster events reported in tofacitinib clinical trials, 13 the majority of herpes zoster infections in the PMS dataset were categorised as not serious.…”

Editorial: real‐world safety of tofacitinib in ulcerative colitis

“…In the OCTAVE trials, nearly half of patients were anti‐TNF‐naïve and prior treatment with vedolizumab was not allowed 2 . In the integrated analyses of infections throughout the global tofacitinib UC clinical programme, prior failure to anti‐TNF was a significant risk factor for herpes zoster (HR 1.76, 95% CI 1.13‐2.74] 9 . Remarkably, none of the real‐world studies included in the review reported major adverse cardiovascular events or thromboembolic complications 8 .…”