Safety of Tofacitinib for Treatment of Ulcerative Colitis, Based on 4.4 Years of Data From Global Clinical Trials

Sandborn, William J.; Panés, Julián; D’Haens, Geert; Sands, Bruce E.; Su, Chinyu; Moscariello, Michele; Jones, Thomas V.; Pedersen, Ron; Friedman, Gary S.; Lawendy, Nervin; Chan, Gary

doi:10.1016/j.cgh.2018.11.035

Cited by 206 publications

(204 citation statements)

References 16 publications

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“…The incidence rate of herpes zoster was numerically higher in the dose escalation subpopulation (who received tofacitinib 10 mg b.d. in OCTAVE Open) than in the overall tofacitinib UC programme . The majority of herpes zoster cases that occurred had resolved without complications, and patients were able to continue tofacitinib treatment or resume treatment following temporary discontinuation, consistent with the management of herpes zoster across other tofacitinib disease populations …”

Section: Discussionmentioning

confidence: 68%

“…6 The safety profile of tofacitinib in the UC clinical programme appeared similar to that reported in patients with rheumatoid arthritis and-with the exception of higher rates of herpes zoster infectionsimilar to biologic therapies for the treatment of UC. 7 Dose-related increases in the rate of herpes zoster infections observed during OCTAVE Sustain 5,7,8 and an increased incidence of venous thromboembolic events manifested as pulmonary embolism events observed in patients treated with tofacitinib 10 mg twice daily (b.d.) compared to tofacitinib 5 mg b.d.…”

Section: Introductionmentioning

confidence: 99%

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

Sands

Armuzzi

Marshall

et al. 2019

Aliment Pharmacol Ther

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SUMMARY Background For patients with UC, flexible maintenance dosing therapy may confer advantages for safety, efficacy, costs and patient preference. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Aim To assess the efficacy and safety of tofacitinib dose de‐escalation and escalation in patients with UC. Methods We evaluated data (November 2017 data cut‐off) from OCTAVE Open, an ongoing, open‐label, long‐term extension study. The dose de‐escalation group comprised 66 tofacitinib induction responders in remission following 52 weeks' tofacitinib 10 mg b.d. maintenance therapy, subsequently de‐escalated to 5 mg b.d. in OCTAVE Open. The dose escalation group comprised 57 tofacitinib induction responders who experienced treatment failure while receiving 5 mg b.d. maintenance therapy, subsequently escalated to 10 mg b.d. in OCTAVE Open. Results After tofacitinib de‐escalation, 92.4% (61/66) and 84.1% (53/63) of patients maintained clinical response and 80.3% (53/66) and 74.6% (47/63) maintained remission, at months 2 and 12, respectively. After dose escalation, 57.9% (33/57) and 64.9% (37/57) of patients recaptured clinical response and 35.1% (20/57) and 49.1% (28/57) were in remission, at months 2 and 12, respectively. The incidence rate of herpes zoster with dose escalation (7.6 patients with events/100 patient‐years) was numerically higher than in the overall tofacitinib UC programme. Conclusions Following tofacitinib de‐escalation in patients already in remission on 10 mg b.d., most maintained remission, although 25.4% lost remission, at month 12. For induction responders who dose‐escalated following treatment failure on 5 mg b.d. maintenance therapy, 49.1% achieved remission by month 12. (ClinicalTrials.gov number: NCT01470612).

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

Sands

Armuzzi

Marshall

et al. 2019

Aliment Pharmacol Ther

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“…in any phase 2, phase 3 or OLE study (data as of September 2018; database not locked). Study designs were described previously …”

Section: Methodsmentioning

confidence: 99%

“…Study designs were described previously. [1][2][3]27 DVT and PE events were identified using clinically relevant pre- [2]; one patient died due to one of the events assessed as severe). Each of the events in the overall tofacitinib-treated cohort occurred during the OLE study; all patients were from the predominant dose tofacitinib 10 mg b.d.…”

Section: Materials S and Me Thodsmentioning

confidence: 99%

Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme

Sandborn

Panés

Sands

et al. 2019

Aliment Pharmacol Ther

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136

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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.

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“…Side effects profile of tofacitinib for patients with AA is comparable to that reported for rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis. However, malignancies and gastrointestinal perforations occurred when tofacitinib was used for these indications contrary to AA (Dhillon, 2017;Sandborn et al, 2018).…”

Section: Dear Editormentioning

confidence: 99%

Clinical experiences on alopecia areata treatment with tofacitinib: A study of 63 patients

Serdaroğlu

Engın

Çelik

et al. 2019

Dermatologic Therapy

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Safety of Tofacitinib for Treatment of Ulcerative Colitis, Based on 4.4 Years of Data From Global Clinical Trials

Cited by 206 publications

References 16 publications

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

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

Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme

Clinical experiences on alopecia areata treatment with tofacitinib: A study of 63 patients

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