Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered high-dose tofacitinib (20 mg) after they had no response to steroid therapy comprising a dose of 1 to 1.5 mg/kg/day. Screening was performed to confirm that these patients had no cardiovascular system or thrombotic system problems before tofacitinib treatment. All patients underwent a laboratory examination, stool testing for Clostridium difficile, and endoscopic biopsies for cytomegalovirus. Tofacitinib has 70% hepatic metabolism and 30% renal metabolism; therefore, patients with hepatic dysfunction and renal dysfunction require a reduced dose. During this case series, no patients required a dose reduction.
This study included a total of eight patients with ASUC. There were four (50%) men and four (50%) women with a median age of 47.1 years (range, 19-65 years). All patients had a median UC duration of 4 years (range, 0-20 years). Four patients had not experienced UC previously. All patients were bio-naïve before starting tofacitinib. Table 1 summarizes the baseline characteristics and laboratory data of the eight patients. Relevant clinical data were retrospectively surveyed by evaluating the electronic medical records of the patients. The Ulcerative Colitis Disease Activity Index (UCDAI) (12) and Mayo scoring system (13) were used to confirm the severity of the general condition of the patients. Defecation frequency, rectal bleeding, mucosal appearance on colonoscopy, physician’s rating of disease activity, gastrointestinal symptoms, adverse events, and drug changes were recorded. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. A clinical response was determined as an improvement of 3 points or more in the UCDAI score and Mayo score. Clinical remission was determined as a UCDAI score and Mayo score of 2 points or less.
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A clinical response was observed in six of the eight patients before they experienced remission. Six patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. When we used tofacitinib during induction and the follow-up phase, only one patient (patient 4) experienced a major adverse event, herpes zoster, which could be treated with acyclovir without stopping tofacitinib.
Patient 1 was a 60-year-old man admitted to the hospital on February 1, 2020. His previous treatment was azathioprine because of intolerance to 5-aminosalicylic acid (5-ASA). The test results showed C-reactive protein (CRP) of 193 mg/dL, albumin (Alb) of 1.8 g/dL, and hemoglobin (Hb) of 8.4 g/dL. His UCDAI score and Mayo score were 12. He underwent colonoscopy (Figure 1a) and was administered tofacitinib after steroid resistance was observed. A clinical response was observed approximately 3 days after treatment administration. He was discharged from the hospital after clinical remission on March 3, 2020 (Figure 1b).
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Patient 2 was a 19-year-old woman admitted to the hospital on May 16, 2020. She had not been administered treatment previously and experienced her first onset of acute UC. The test results showed CRP of 71 mg/dL, Alb of 2.0 g/dL, and Hb of 4.7 g/dL. Her UCDAI score and Mayo score were 12. She was administered tofacitinib after steroid resistance was observed. Because there was no clinical response to tofacitinib, remission was achieved after switching from tofacitinib to infliximab (5mg/kg) at 5 days after its administration. She had a great response to infliximab and was discharged from the hospital after clinical remission on June 25, 2020.
Patient 3 was a 53-year-old woman admitted to the hospital on October 24, 2018. Her previous treatment was 5-ASA. The test results showed CRP of 7 mg/dL, Alb of 2.7 g/dL, and Hb of 8.6 g/dL. Her UCDAI score and Mayo score were 12. She underwent colonoscopy (Figure 2a) and was administered tofacitinib after steroid resistance was observed. A clinical response was observed approximately 2 days after treatment administration. She was discharged from the hospital after clinical remission on December 14, 2018 (Figure 2b).
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Patient 4 was a 52-year-old woman admitted to the hospital on August 1, 2019. Her previous treatment was 5-ASA. The test results showed CRP of 241 mg/dL, Alb of 1.3 g/dL, and Hb of 6.3 g/dL. Her UCDAI score and Mayo score were 12. She underwent colonoscopy (Figure 3a) and was administered tofacitinib after steroid resistance was observed. A clinical response was observed approximately 4 days after treatment administration. She developed herpes zoster as she had never been vaccinated for it. However, she was cured with anti-viral drug combination, without stopping tofacitinib. She was discharged from the hospital after clinical remission on September 18, 2019 (Figure 3b).
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Patient 5 was 65-year-old man admitted to the hospital on August 1, 2019. He had not been administered treatment previously and experienced his first onset of acute UC. He was referred to the hospital by his former physician because of severe bloody stools. The test results showed CRP of 3 mg/dL, Alb of 2.7 g/dL, and Hb of 9.3 g/dL. His UCDAI score and Mayo score were 12. He underwent colonoscopy (Figure 4a) and was administered tofacitinib after steroid resistance was observed. A clinical response was observed 3 days after treatment administration. He was discharged from the hospital after clinical remission on December 8, 2019 (Figure 4b).
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Patient 6 was a 20-year-old man admitted to the hospital on November 25, 2019. He had not been administered previous treatment because of intolerance to 5-ASA. The test results showed CRP of 241 mg/dL, Alb of 1.3 g/dL, and Hb of 6.3 g/dL. His UCDAI score and Mayo score were 12. He was administered tofacitinib after steroid resistance was observed. Because there was no clinical response to tofacitinib, remission was achieved after switching from tofacitinib to infliximab at 5 days after its administration. However, there was no clinical response to infliximab. Finally, he underwent total colectomy. He was discharged from the hospital after clinical remission on December 25, 2019.
Patient 7 was a 65-year-old man admitted to the hospital on November 18, 2020. He had not been administered treatment previously and experienced his first onset of acute UC. He was referred to the hospital by his former physician because of severe bloody stools The test results showed CRP of 15.8 mg/dL, Alb of 1.4 g/dL, and Hb 8.7 of g/dL. His UCDAI score and Mayo score were 12. He was administered tofacitinib after steroid resistance was observed. A clinical response was observed approximately 3 days after treatment administration. He was discharged from the hospital after clinical remission on December 26, 2020.
Patient 8 was a 51-year-old man admitted to the hospital on January 30, 2021. He had not been administered any previous treatment because of intolerance to 5-ASA. The test results showed CRP of 5.6 mg/dL, Alb of 1.4 g/dL, and Hb of 9.6 g/dL. His UCDAI score and Mayo score were 12. He underwent colonoscopy (Figure 5a) and was administered tofacitinib after steroid resistance was observed. A clinical response was observed approximately 5 days after treatment administration. He was discharged from the hospital after clinical remission on February 27, 2021 (Figure 5b).