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

Sands, Bruce E.; Armuzzi, Alessandro; Marshall, John K.; Lindsay, James O.; Sandborn, William J.; Danese, Silvio; Panés, Julián; Bressler, Brian; Colombel, Jean Fréd́eric; Lawendy, Nervin; Maller, Eric S.; Zhang, Haiying; Chan, Gary; Salese, Leonardo; Tsilkos, Konstantinos; Marren, Amy; Su, Chinyu

doi:10.1111/apt.15555

Cited by 68 publications

(79 citation statements)

References 24 publications

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“…Furthermore, physicians might prefer a higher maintenance dose due to the limited alternative therapeutic options remaining. The OCTAVE open programme showed a recapture of response rate of 64.9% (37/57) after dose escalation, indicating that dose escalation could be an option for secondary nonresponders before switching out of class . Receiving 10 mg twice daily at week 12 was not associated with adverse events, however, cohorts with longer follow‐up are needed to determine this effect.…”

Section: Discussionmentioning

confidence: 98%

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Biemans

Sleutjes

Vries

et al. 2020

Aliment Pharmacol Ther

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Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in | 881 BIEMANS Et Al. How to cite this article: Biemans VBC, Sleutjes JAM, de Vries AC, et al; on behalf of the Dutch Initiative on Crohn and Colitis (ICC). Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry. Aliment Pharmacol Ther. 2020;51:880-888. https://doi.

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Section: Discussionmentioning

confidence: 98%

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Biemans

Sleutjes

Vries

et al. 2020

Aliment Pharmacol Ther

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“…After tofacitinib de-escalation, 74.6% (47/63) maintained remission after 12 months, while after dose escalation, 35.1% (20/57) and 49.1% (28/57) were in remission at months 2 and 12, respectively. 51 Although the study design and the small sample size could limit the clinical significance of these findings, this study highlights a high rate of efficacy after tofacitinib dose modulating, which could be explained with the low immunogenicity of such small molecule compared to biologics. Larger studies and longer follow-up are needed to further address this point.…”

Section: Results From Clinical Trials and Real-world Studiesmentioning

confidence: 79%

“…A recent open-label, long-term extension study of the OCTAVE trials (OCTAVE open) evaluated the efficacy and safety of tofacitinib dose escalation or de-escalation in patients receiving 5 mg or 10 mg twice daily after 52 weeks. 51 Sixty-six patients receiving maintenance therapy with tofacitinib 10 mg twice daily who were in remission at week 52 underwent de-escalation at 5 mg (de-escalation group), while 57 patients who experienced an UC flare during maintenance therapy with 5 mg twice daily underwent escalation to 10 mg twice daily (escalation group). After tofacitinib de-escalation, 74.6% (47/63) maintained remission after 12 months, while after dose escalation, 35.1% (20/57) and 49.1% (28/57) were in remission at months 2 and 12, respectively.…”

Section: Results From Clinical Trials and Real-world Studiesmentioning

confidence: 99%

“…All cases of herpes zoster infection in patients treated with tofacitinib have been reviewed in a work from Winthrop et al, which included the cases from the open-label study OCTAVE Open. 51,56 The Authors reported 65 cases of herpes zoster infection, with an overall rate of 5.6%. Only one case of encephalitis was described, which resolved upon standard treatment, and five cases (7.7%) led to treatment discontinuation.…”

Section: Tofacitinib In Ulcerative Colitis: Safetymentioning

confidence: 99%

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<p>Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors</p>

Troncone¹,

Marafini²,

Blanco³

et al. 2020

CEG

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Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD) in human beings, are chronic relapsing-remitting disorders of the gastrointestinal tract, which usually require lifelong therapies. For many years, IBD have been managed with corticosteroids, aminosalicylates and immunosuppressants (ie, thiopurines). The advent of biologic therapies (anti-TNF-α agents) has significantly improved the outcome of IBD patients in terms of prolonged clinical remission, corticosteroid sparing, achievement of mucosal healing and prevention of disease-related complications. Nevertheless, primary failure or loss of response to biologics occur in about 50% of patients treated with these drugs. Therefore, the need for new effective treatments for such patients has critically emerged as an urgent priority. With this regard, several small-molecule drugs (SMDs) targeting lymphocyte trafficking (ie, sphingosine-1-phosphate receptor modulators) and the JAK/STAT pathway (eg, tofacitinib) have been recently developed and tested in IBD. In particular, JAK inhibitors are oral compounds characterized by short half-life, low antigenicity and the ability to dampen several pro-inflammatory pathways simultaneously. Tofacitinib, a pan-JAK inhibitor, has shown good efficacy and safety in UC clinical trials and has been recently approved for the treatment of UC patients. In this review, we analyze the main evidence supporting the use of JAK inhibitors in UC and explore the unanswered questions about the use of this class of drug in UC.

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“… 30 We also recommend a trial of de-escalation to the maintenance dose of 5 mg twice daily from 10 mg twice daily, once the patient is in endoscopic remission. 3 , 31 …”

Section: Venous Thromboembolismmentioning

confidence: 99%

JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications

Agrawal

Kim

Colombel

2020

Journal of Crohn's and Colitis

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Janus kinase inhibitors (JAKi) are a new class of small molecule drugs that modulate inflammatory pathways by blocking one or more JAK receptors, and are increasingly being used in the treatment of immune-mediated diseases. Tofacitinib, a non-selective JAKi, is now approved for moderate-to-severe ulcerative colitis (UC) that is refractory or intolerant to tumor necrosis factor inhibitors (TNFi). While tofacitinib is associated with the advantages of oral administration, rapid onset of action, and lack of immunogenicity over TNFi, there are many safety considerations to take into account such as the risk of thromboembolism, infections and hyperlipidemia; each with specific nuances pertaining to prevention and monitoring strategies. Considerations such as pregnancy, breastfeeding and history of malignancy also are to be navigated with utmost caution, given that very few data are available for guidance. With the use of JAKi in the real world progressively over time, safety implications will become more lucid, including caveats pertaining to JAK selectivity and gut-selective JAKi, as well as mechanistic data pertaining to adverse effects. This viewpoint serves as a practical guide for clinicians managing IBD patients to navigate safety concerns around JAKi, including preventive and monitoring strategies.

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

Cited by 68 publications

References 24 publications

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

<p>Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors</p>

JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications

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