OBJECTIVE: Tofacitinib, an oral Janus kinase inhibitor, is approved for the treatment of moderate to severe ulcerative colitis (UC). We evaluated clinical and endoscopic efficacy, safety and drug survival of tofacitinib up to one year in a real-world cohort.
METHODS: In this retrospective cohort study, 36 UC patients were included who received tofacitinib. The primary outcome was combined with steroid-free clinical remission [Simple Clinical Colitis Activity Index (SCCAI) ≤2] and endoscopic improvement (Mayo score ≤1) at 52 weeks. Secondary outcomes included clinical (SCCAI drop ≥3) and endoscopic response (Mayo score drop ≥1), biochemical remission [fecal calprotectin (FC) ≤150 mg/kg and C-reactive protein ≤5 mg/L), safety and drug survival.
RESULTS: Median disease duration was 7 (3-14) years and 89 and 42% of patients failed prior anti-tumor necrosis factor (anti-TNF) and vedolizumab treatment, respectively. Combined corticosteroid-free clinical remission and endoscopic improvement were observed in 8/36 patients (22%), 6/35 (17%) and 12/31 (39%), at 16, 36 and 52 weeks, respectively. Corresponding combined clinical and endoscopic response rates were 15/36 (42%), 12/35 (34%), 15/31 (48%) and biochemical remission rates were 11/33 (33%), 10/32 (31%) and 10/29 (34%). Nine infections (two herpes zoster) led to dose reduction or (temporary) drug withdrawal. Permanent withdrawal occurred in 14/36 patients (33%) after a median duration of 9 (5-30) weeks. Drug survival at 1 year was 60%. Patients that failed anti-TNF were less likely to discontinue tofacitinib treatment early compared to patients without prior anti-TNF use (hazard ratio 0.20, 95% confidence interval 0.06-0.65).
CONCLUSION: In a refractory UC population, combined steroid-free clinical remission and endoscopic improvement were found in 39% of patients at 1 year.
AIM: To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life.
METHODS: Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16.
RESULTS: A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1-0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3-0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1-0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3-1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events.
CONCLUSIONS: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.
BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib.
METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs.
RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day).
CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.
AIM: The literature regarding monoclonal antibodies and increased postoperative complications in inflammatory bowel disease remains controversial. There have been no studies investigating tofacitinib. The aim of this work was to determine preoperative exposure to the small-molecule inhibitor tofacitinib and postoperative outcomes.
METHOD: We conducted a retrospective review of all adult patients exposed to tofacitinib within 4 weeks of total abdominal colectomy for medically refractory ulcerative colitis between 1 January 2018 and 1 September 2020 at four inflammatory bowel disease referral centres. Data collected included patient demographics and 90-day postoperative morbidity, readmission and reoperation rates.
RESULTS: Fifty-three patients (32 men, 60%) with ulcerative colitis underwent a total abdominal colectomy (n = 50 laparoscopic, 94%) for medically refractory disease. Previous exposure to monoclonal antibodies included infliximab (n = 34), adalimumab (n = 35), certolizumab pegol (n = 5), vedolizumab (n = 33) and ustekinumab (n = 10). Twenty-seven (51%) patients were on concurrent prednisone at a median daily dose of 30 mg by mouth (range 5-60 mg). There were no postoperative deaths. Ninety-day postoperative complications included ileus (n = 7, 13.2%), superficial surgical site infection (n = 4, 7.5%), intra-abdominal abscess (n = 2, 3.8%) and venous thromboembolism (VTE) (n = 7, 13.2%). Locations of VTE included portomesenteric venous thrombus (n = 4), internal iliac vein (n = 2) and pulmonary embolism (n = 1). Nine (17%) patients were readmitted to hospital and five (9%) patients had a reoperation.
CONCLUSION: Mirroring the recently issued US Food and Drug Administration black box warning of an increased risk of VTE in medically treated ulcerative colitis patients taking tofacitinib, preoperative tofacitinib exposure may present an increased risk of postoperative VTE events. Consideration should be given for prolonged VTE prophylaxis on hospital discharge.
Revista»Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
BACKGROUND: Phase III trials demonstrated effectiveness of tofacitinib, an oral Janus kinase inhibitor, to induce and maintain remission in patients with moderate-to-severe active ulcerative colitis (UC).
AIMS: We report the real-world effectiveness and safety of tofacitinib in patients with UC in France.
METHODS: From February 2017 to December 2018, we performed a national French cohort study, which included all consecutive patients with an active UC refractory to anti-TNF and vedolizumab, who received tofacitinib. Outcomes were survival without colectomy, survival without tofacitinib discontinuation and steroid-free clinical remission at weeks 14, 24 and 48.
RESULTS: Thirty-eight patients were included, with a median follow-up of 41.5 (18.5-56.8) weeks. Survival without colectomy was 77% [95% confidence interval (95%CI): 59.3-87.9] at week 24 and 70% (95%CI: 50.9-82.8) at week 48. Survival without treatment discontinuation was 70% (95%CI: 52.6-82.3) at week 24. Steroid-free clinical remission was observed in 13 (34%) patients at week 48. Adverse events occurred in 14 (37%) patients, including 6 severe adverse events and three herpes zoster infections.
CONCLUSION: In a highly refractory UC population, one third of patients treated with tofacitinib achieved steroid-free clinical remission at week 14 and 70% of patients avoided colectomy at one year, with an acceptable safety profile. These data confirm tofacitinib effectiveness in UC, especially after multiple biologic failures.
(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy.
