Upadacitinib Results in Endoscopic Remission in Patients With Inflammatory Bowel Disease and Prior Tofacitinib Failure

Journal of Clinical Gastroenterology · 2025-03-06 · 2 citations

GOALS: Assess the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure. BACKGROUND: Patients with severe, refractory Crohn's disease (CD) or ulcerative colitis (UC) and inadequate response to medical therapy have a high risk of complications. A better understanding of treatment response in the setting of prior failure may improve disease control in high-risk patients. Currently, the response to a subsequent Janus Kinase (JAK) inhibitor after prior JAK failure is poorly understood. STUDY: We retrospectively assessed the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure. RESULTS: We report on 26 patients (10 UC, 16 CD) treated with upadacitinib after tofacitinib failure. Mean age 40.2 years, mean disease duration 14.4 years (range 2 to 33), and previously failed a median of 5 advanced therapies. The mean upadacitinib treatment duration was 13.9 months (SD 4.5). On upadacitinib, 83.3% (n=10/12) of patients achieved clinical response, 66.7% (n=8/12) clinical remission, 71.4% (n=10/14) endoscopic improvement, 57.1% (n=8/14) endoscopic remission, and 35.7% (n=5/14) endoscopic healing. The mean Simple Endoscopic Score in CD decreased from 14.3 (SD: 8.3) to 8.6 (SD: 9.0) ( P =0.24). The mean Mayo Endoscopic Subscore significantly decreased from 2.7 (SD 0.8) to 0.9 (SD 1.2) ( P =0.006). 73.1% of patients on upadacitinib reported adverse events, most commonly minor infections and acne. No serious adverse events, major cardiovascular events, malignancies, or Shingles were observed. CONCLUSIONS: Upadacitinib was tolerated in most patients and resulted in clinical and endoscopic improvement in the majority of patients with severe, refractory CD or UC with prior tofacitinib failure, regardless of previous clinical response to tofacitinib. Further studies would define the long-term safety, efficacy, and predictors of response after previous JAK exposure.

Tu1925: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF VEDOLIZUMAB IN PATIENTS WITH ILEAL CROHN’S DISEASE

Gastroenterology · 2025-05-01

Mycophenolate Mofetil Appears Effective for the Treatment of Patients With Refractory Crohn’s Disease

Crohn s & Colitis 360 · 2024-10-01

Background: Medically refractory Crohn's disease (CD) is associated with a high risk of complications. Mycophenolate mofetil (MMF), a small molecule immunosuppressant, has limited data in patients with CD, and objective endoscopic response to MMF has not been reported. Aims: We evaluated the safety and clinical, endoscopic, and biochemical effectiveness of off-label MMF for refractory CD as monotherapy or in combination with a biologic in patients with CD. Methods: We retrospectively assessed adverse events (AEs), clinical response (Harvey-Bradshaw index), endoscopic response (simple endoscopic score in Crohn's disease), and physician global assessment at an academic medical center and county hospital. Results: = 20) between 2008 and 2021 at a dose ranging from 1000 to 4000 mg daily. Median age was 39 years and median disease duration was 12 years. All patients previously failed ≥ 1 advanced therapy (median = 4). The median MMF therapy duration was 27 weeks. 54% achieved clinical response and 19% achieved clinical remission after a mean of 19.5 weeks (SD 14.5). Endoscopic response occurred in 32%, endoscopic remission in 16%, and endoscopic healing in 4% after a mean of 46.6 weeks (SD 31.0). 48% of patients experienced AEs, most commonly mild infection, nausea/vomiting, and headache. One serious AE occurred, which was assessed as unrelated to MMF. Conclusions: MMF resulted in clinical, endoscopic, and biochemical benefits in some patients with refractory CD, and was tolerated by most patients. Further randomized controlled trials are needed to define optimal dosing and long-term efficacy and safety.

Colonoscopy Outreach for Rural Communities (CORC): A study protocol of a pragmatic randomized controlled trial of a patient navigation program to improve colonoscopy completion for colorectal cancer screening

Contemporary Clinical Trials · 2024-04-12 · 3 citations

10.5: Inflammatory Bowel Disease

2023-02-01 · 2 citations

Textbook for the Adult-Gerontology Acute Care Nurse Practitioner

2023-02-01 · 1 citations

Deep Remission in Severe Refractory Crohn’s Disease With Mycophenolate Mofetil

Inflammatory Bowel Diseases · 2022-10-12 · 2 citations

Studies using mycophenolate mofetil (MMF) in Crohn’s disease (CD) are limited. We present a case of robust response to MMF in a patient with CD. A 34-year-old woman with a 24-year history of ileocolonic CD was refractory to infliximab, adalimumab, certolizumab, vedolizumab, and ustekinumab. Colonoscopy showed severe ileocolitis (Figure 1A). Symptoms included abdominal pain and diarrhea and B12, zinc, and iron deficiency. ... Given her refractory CD, MMF was initiated and increased to 1000 mg twice daily with rapid symptom resolution. C-reactive protein (CRP) dropped from 44.8 mg/L to 7.9 mg/L (reference 0-10 mg/L) after 3 months (Figure 1). After 11 months on MMF, off-label tofacitinib was started and MMF discontinued. After 6 months, her abdominal pain and diarrhea returned and colonoscopy showed severe ileocolitis and a new perianal fistula. CRP increased from 4.3 to 141 mg/L. MMF was restarted and uptitrated to 2000 mg twice daily. After 6 months, CRP normalized and colonoscopy demonstrated ileocecal valve stenosis but otherwise no endoscopic inflammation (Figure 1B). Three years since restarting MMF, she has no medication side effects, remains in remission, and CRP is 0.5 mg/L (Figure 1). Monitoring includes complete metabolic panel, complete blood count, and CRP quarterly and colonoscopy annually.

Tofacitinib Appears Well Tolerated and Effective for the Treatment of Patients with Refractory Crohn’s Disease

Digestive Diseases and Sciences · 2022 · 11 citations

• Medicine
• Internal medicine
• Surgery

RELATIONSHIP BETWEEN SELF-REPORTED SLEEP AND DISEASE ACTIVITY DIFFERS BASED ON ENDOSCOPIC OR CLINICAL DISEASE ACTIVITY MEASURES

Gastroenterology · 2022-01-20 · 1 citations

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn’s Disease

Inflammatory Bowel Diseases · 2021 · 33 citations

• Medicine
• Internal medicine
• Gastroenterology

BACKGROUND: The majority of patients with Crohn's disease (CD) will not achieve endoscopic remission on current therapy. Addition of tofacitinib to biologics may improve remission rates. METHODS: We retrospectively assessed safety and clinical and endoscopic effectiveness of off-label tofacitinib and biologics for CD. RESULTS: We identified 19 patients treated with tofacitinib and a biologic for refractory CD between 2017 and 2019. Tofacitinib was added for luminal disease on colonoscopy (n = 13), luminal disease on capsule (n = 3), and pyoderma gangrenosum (n = 3). The mean age was 41.2 years (28-62), mean disease was duration 16.9 years (6-36), and prior exposure to biologics was a median of 4 (1-6). Mean treatment duration was 9.6 months (SD, 3.3). Adverse events (AEs) were reported in 36.8% of patients, most commonly minor infection or CD flare, and no patients had a serious AE; 80.0% (n = 8) achieved clinical response, and 60.0% (n = 6) achieved clinical remission based on Harvey-Bradshaw Index. Endoscopic improvement occurred in 54.5% (n = 6), endoscopic remission in 18.2% (n = 2), and endoscopic healing in 18.2% (n = 2) of patients. Mean Simple Endoscopic Score in CD significantly improved from 13.6 ± 5.2 to 6.5 ± 4.0 after treatment (P < .01). CONCLUSIONS: In patients treated with tofacitinib in combination with a biologic, no new safety signals were observed. Combination tofacitinib and a biologic was effective in achieving clinical and endoscopic improvement in some patients with severe, refractory CD, although a larger sample size is needed to further assess the efficacy and long-term safety of this treatment strategy.