Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial

Vermeire, Séverine; Su, Chinyu; Lawendy, Nervin; Taku, Keisei; Sandborn, William J.; Rubin, David T.; Modesto, Irene; Gardiner, Sean; Kulisek, Nicole; Zhang, Haiying; Wang, Wenjin; Panés, Julián

doi:10.1093/ecco-jcc/jjaa249

Cited by 44 publications

(46 citation statements)

References 27 publications

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“…Remission at 6 months (MES ≤1, Mayo stool frequency subscore ≤1, RBS 0) was 77.1% and 90.0% in the 5 and 10 mg BD subgroups, respectively, with an adjusted treatment difference between the two groups of 12.9% (95% CI 0.5-25.0). 27 Deep endoscopic remission and no previous anti-TNF failure were factors predictive of maintenance of remission after de-escalation. Thus, endoscopic assessment and consideration of a patient's prior treatment history should be considered before dose reduction.…”

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 94%

“…In the largest real-world cohort to date, Honap et al evaluated the efficacy of tofacitinib in 134 patients with UC from four centres in the United Kingdom. 28 In contrast to the relatively lower rates of prior anti-TNF exposure included in the OCTAVE 1 and 2 cohorts (53% and 55%, respectively), 20 the majority in the Honap et al study cohort (80%) were previously treated with anti-TNF, 27 reflecting the more complex and treatment refractory patients typically included in real-world data. By week 8, 74% achieved clinical response, and by week 26, 44% patients achieved CFCR.…”

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 97%

“…AEs were similar across both dosage groups and consistent with previously reported safety profiles. 27 'Real-world' experience of tofacitinib in UC A growing body of evidence from real-world data for tofacitinib supports the effectiveness of tofacitinib in the more complex and diverse patient populations seen in the OCTAVE studies (Table 1).…”

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 99%

“…The recently published primary analysis from RIVETING aimed to assess the outcomes of dose de-escalation in patients in stable remission. 27 Patients on 10 mg BD dosing for ≥2 years were randomized 1:1 to de-escalate to 5 mg BD or continue 10 mg BD. Remission at 6 months (MES ≤1, Mayo stool frequency subscore ≤1, RBS 0) was 77.1% and 90.0% in the 5 and 10 mg BD subgroups, respectively, with an adjusted treatment difference between the two groups of 12.9% (95% CI 0.5-25.0).…”

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 99%

See 3 more Smart Citations

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease—where we are and where we are going

Liu¹,

Aslam²,

Nigam³

et al. 2022

DIC

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Inflammatory bowel diseases, comprising ulcerative colitis (UC) and Crohn's disease, are chronic, immune-mediated and progressive inflammatory disorders affecting the gastrointestinal tract. Tofacitinib is the first oral small-molecule Janus kinase (JAK) inhibitor licensed and approved by the National Institute for Health and Care Excellence (NICE) for use in moderately-to-severely active UC after intolerance, inadequate response, or loss of response to conventional treatment or biologic therapy. The pivotal OCTAVE studies demonstrated the efficacy and safety of tofacitinib for the induction and maintenance of remission in UC. A growing body of evidence from real-world data supports the positive clinical and endoscopic benefits observed with tofacitinib treatment in the OCTAVE trials. This narrative review summarizes the current literature regarding the mechanism of action of tofacitinib, data from registrational trials, emerging real-world evidence, and an overview of the most recent safety evidence. We explore evolving treatment paradigms, including the use of tofacitinib in the COVID-19 era, pregnancy and extraintestinal manifestations, as well as the emerging concept of combining tofacitinib with biological therapy. We will also present a brief overview of the next generation of JAK inhibitors in the pipeline.

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Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 94%

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 97%

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 99%

Section: Outcomes Of Dose Reduction and Escalationmentioning

confidence: 99%

See 2 more Smart Citations

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease—where we are and where we are going

Liu¹,

Aslam²,

Nigam³

et al. 2022

DIC

View full text Add to dashboard Cite

show abstract

“…A following dosing regimen is recommended by the National Institute of Health and Care Excellence for patients with UC: 10 mg twice daily for 8 weeks (induction phase) and 5 mg twice daily as a maintenance [ 20 ]. Accordingly, a recent RIVETING trial hinted that dose de-escalation from 10 mg to 5 mg twice daily in patients with UC with remission and anti-TNF-α naive, was safe [ 21 ].…”

Section: Non-selective Jak Inhibitorsmentioning

confidence: 99%

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Dudek

Fabisiak

Zatorski

et al. 2021

JCM

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Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD.

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Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure

Panés,

D’Haens,

Sands

et al. 2024

UEG Journal

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Background and AimsTofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report an integrated summary of tofacitinib safety from the completed global UC clinical program (9.2 years maximum tofacitinib exposure).MethodsThis analysis included patients receiving tofacitinib 5 or 10 mg twice daily (b.i.d.) from completed phase 2/3 placebo‐controlled studies, an open‐label, long‐term extension study and a randomized phase 3b/4 study. Proportions and incidence rates (IRs; unique patients with events/100 patient‐years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest (AESI).ResultsOverall, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg b.i.d.; 938 (81.1%) were in the predominant dose tofacitinib 10 mg b.i.d. group; 552 (47.7%) received tofacitinib for ≥2 years; total exposure: 3202.0 PY; 994 (85.9%) experienced AEs; 254 (22.0%) experienced serious AEs. Median treatment duration: 1.7 (range 0.0–9.2) years. IRs (95% CI) for combined tofacitinib doses: deaths 0.24 (0.10–0.48); serious infections (SIs) 1.80 (1.37–2.32); herpes zoster (HZ; non‐serious and serious) 3.24 (2.63–3.94); serious HZ 0.24 (0.10–0.48); opportunistic infections 0.96 (0.65–1.36); malignancies (excluding non‐melanoma skin cancer [NMSC]) 0.88 (0.59–1.26); NMSC 0.71 (0.45–1.07); major adverse cardiovascular events 0.27 (0.12–0.52); deep vein thrombosis 0.06 (0.01–0.22); pulmonary embolism 0.18 (0.07–0.40); and gastrointestinal perforations 0.09 (0.02–0.27).ConclusionsExcept for HZ and SIs, IRs for AESI were <1 case/100 PY. Safety was consistent with previous analyses of shorter exposure and tofacitinib's known safety profile, including real‐world data.ClinicalTrials.govNCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT03281304.

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Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial

Cited by 44 publications

References 27 publications

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease—where we are and where we are going

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease—where we are and where we are going

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure

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