Use of Tofacitinib as an Alternative in Moderately Severe Ulcerative Colitis in Pediatric Patients Refractory to Tumor Necrosis Factor Inhibitor Therapy

Background: In infants and adolescents, Ulcerative colitis (UC) onset is characterized by rapid progression, with more extensive forms of the disease, making its treatment a challenge. While in adults, in cases of moderate-severe UC, biologic therapy is recommended, including tumor necrosis factor inhibitors (anti-TNF), anti-integrin alpha-4-beta-7 (vedolizumab), and anti-interleukin-12-interleukin-23 (ustekinumab). In the pediatric patient, long-term treatment is required for patients to remain in remission, the therapeutic arsenal available is narrower, since neither vedolizumab nor ustekinumab is approved, and most of the evidence about these therapies is observational, making the outlook somewhat more difficult. Evidence on the efficacy of tofacitinib in pediatric patients refractory to tumor necrosis factor inhibitors is scarce. The objective is to describe the efficacy and safety, in real world, of pediatric patients refractory to tumor necrosis factor inhibitors treated with tofacitinib. Methods: Observational study, sociodemographic and clinical variables were collected from pediatric patients (those aged 2 to 17 years, according to national legislation) with moderate-severe UC refractory to tumor necrosis factor inhibitors, both in outpatient and inpatient care between January 2022 and June 2023 in pediatric gastroenterology inflammatory bowel disease (IBD) referral centers in different cities of Colombia. Patients received treatment with tofacitinib in induction phase for 8 weeks and then maintenance therapy. Results: 4 female patients, median age 14.32 (SD 2.12; IQR 12.47-16.53) years, all with prior biologic exposure and refractory to tumor necrosis factor inhibitors, and two of them with prior use of anti-integrin. And without a history of extraintestinal manifestations. Clinical, biochemical and endoscopic remission was obtained in 3/4 at induction. Information was obtained from 3 patients in 6-month maintenance, 2/3 remained in clinical, biochemical and endoscopic remission and 1/3 has not achieved biochemical or endoscopic remission. Information was obtained from 1 patient in 12-month maintenance, achieving clinical and biochemical remission, however, endoscopic remission has not been achieved. One patient was initiated for severe acute UC with risk of colectomy, with significant improvement after 7 days, reaching therapeutic objectives at induction. All were discharged from hospital in 8 days on average (SD1.1; IQR 6.4-9). No adverse events were documented throughout the different phases of treatment. No patient required permanent withdrawal of tofacitinib due to adverse events. No thromboembolic or cardiovascular events or leukopenia were reported. No cases of Herpes Zoster were reported. Also, they were able to resume their daily and educational activities, without nonadherence or psychological events. Conclusions: The results of this study are promising. It shows that despite being an ‘off-label’ drug, tofacitinib is an effective and safe alternative in the treatment of moderate to severe UC in pediatric patients refractory to tumor necrosis factor inhibitors, presenting a high percentage of response in induction treatment, sustained over time, and safe. Also, in the context of severe acute UC, the fast-acting profile of this drug should be taken into account, its potential role as rescue therapy, especially in those patients with previous therapeutic failure to infliximab. It is only a matter of time before tofacitinib becomes one of the main therapeutic tools in these patients.