Real-world clinical and endoscopic outcomes after one year tofacitinib treatment in ulcerative colitis

Abstract

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.

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis

“…19 Primary non-response rates were high (44.1%) in this refractory cohort, but in line with previous retrospective series, 7,9,10,12 as was a steroid-free clinical remission rate of 32.2% after 1 year of tofacitinib therapy. 6,10 In the tofacitinib phase III OCTAVE SUSTAIN development programme, endoscopic improvement rates (Mayo endoscopic subscore ≤1, originally defined as mucosal healing in the original OCTAVE protocols) of 37.4% by week 52 have been observed in patients treated with tofacitinib 5 mg BID. 3 Similar to other biological compounds, endoscopic improvement rates at week 52 were higher in anti-TNF naïve (42.6%) versus anti-TNF exposed patients (30.1%).…”

Real-world experience with tofacitinib in ulcerative colitis - a systematic review and meta-analysis

“…Other reasons for treatment discontinuation were adverse events (AE) in 20% of patients (44/241, 95% CI 13-30%) (Supplementary figure 3c), need for colectomy 19 % (29/147, 95% CI 6-47%) and patient request (0.8%, 3/370) (Table 3). Median time to discontinuation of therapy was 9 weeks 19,23,24 .…”

“…Descriptors of tofacitinib efficacy outcomes across real-world studies. 675 676 Clinical response Decrease of ≥2 points38,39 , 3 PMS/ decrease >30% from baseline40,20,24 Decrease ≥1 point on RBS 38 /absolute RBS=0/1 from baseline36,20 Reduction in SSCAI of 323…”

“…Efficacy of tofacitinib treatment across real-world studies in ulcerative colitis patients at induction(8,12,14) and maintenance(16,24,26) timepoints. BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

The Era of Janus Kinase Inhibitors for Inflammatory Bowel Disease Treatment

“…In 2021, Straatmijer et al published a retrospective cohort study that included 36 UC patients who received tofacitinib [15]. The median disease duration was 7 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) years; 89% of the patients had previously failed to respond to anti-TNF treatment and 42% to vedolizumab treatment.…”