Abstract Background Tofacitinib (TOFA), an oral Janus kinase inhibitor, is approved for moderate to severe ulcerative colitis (UC). The aim of this study was to evaluate the effectiveness and safety of dose escalation and de-escalation of TOFA in clinical practice. Methods In this retrospective cohort study, we included UC patients treated with TOFA between January 2018 and July 2023 in the Capital Region of Denmark (≈ 33% of the Danish population). The primary outcome was clinical remission (SCCAI ≤2) and secondary outcomes were steroid-free clinical remission (SFR), secondary loss of response (SLR) and safety. Outcomes were assessed at weeks 8 (W8), 16, 28, and 52 (W52). Logistic regression analyses examined predictors of clinical response/remission at W8 and SFR at W52, while Cox proportional-hazards models evaluated predictors of SLR and SFR, with emphasis on the impact of dose modifications on the clinical outcomes. Results A total of 85 patients were included (Table 1). Clinical remission and SFR were achieved in 43.4% and 34.9% at W8, and 35.3% and 29.4% at W52, respectively. One-third (N = 26 30.6%) were unable to de-escalate dosing after induction; however, 60.0% (N = 6) of the patients who were without prior clinical remission achieved so within four months and de-escalated TOFA dosing. Among patients requiring dose escalation due to SLR (N = 16 18.8%), seven (43.8%) recaptured clinical remission. In Cox analyses, TOFA dosing did not significantly influence SLR (HR 1.86 95% CI 0.82–4.25) nor SFR at 52 weeks (continued high-dose 57.1% vs. de-escalation 47.8%, p = 0.71; HR 1.13 95% CI 0.53–4.45). Early clinical response and remission at W8 was the only clinical factor associated with SFR at W52 (OR 46.3, 95% CI 8.78–856.61, p 0.001). No serious adverse events occurred; however, 40 patients (47.1%) experienced adverse events, with no significant association with dosing escalations, most commonly including hypercholesterolemia, anaemia, nausea, and few cases of herpes zoster reactivation (N = 3 (3.5%)). Conclusion This real-world multicentre study demonstrates that TOFA is effective and safe for inducing and maintaining clinical remission in bio-exposed patients with refractory UC. Dose de-escalation after induction and escalation for SLR were feasible, with no clear long-term efficacy difference between strategies and no new safety concerns. Individualized dosing of TOFA dependent on induction response to improve long-term outcome was in this study safe. Conflict of interest: Ms. Mirza, Hina: No conflict of interest Toma, Maria Bassam Mati: No conflict of interest Rasmussen, Michelle Bjørnshauge: No conflict of interest Seidelin, Jakob Benedict: has received research grants from Takeda, Janssen, the Danish Research Council, and the Capital Region Denmark, and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. Attauabi, Mohamed: Research grants from Novo Nordisk Fonden and Lundbeck Foundation. Personal fees from Eli Lilly, Celltrion, and Lundcbeck foundation, outside the submitted work.
Mirza et al. (Thu,) studied this question.