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

BACKGROUND: Active Crohn's disease increases the risk of strictures, fistulas, and abscesses. Less than 30% of patients with Crohn's disease achieve endoscopic remission on any therapy. Tofacitinib may be a therapeutic option for patients with refractory Crohn's disease. AIMS: We aimed to evaluate the safety and effectiveness of off-label tofacitinib for refractory Crohn's disease. METHODS: We retrospectively assessed adverse events and clinical/endoscopic response after therapy. RESULTS: Forty-four patients were included in the safety analysis and 35 were included in the clinical and/or endoscopic assessments. The mean age was 41.8 years and the mean disease duration was 17.4 years. All patients had prior biologic exposure. Adverse events were reported in 52.3% of patients; 13.6% had ≥ 1 serious adverse event after a median 54.6 weeks of treatment. Seventy percent achieved clinical response after a mean 29.4 (SD 15.1) weeks, and 33.3% achieved clinical remission after a mean 33.4 (SD 17.6) weeks of therapy. Endoscopic improvement occurred in 25.0%, endoscopic remission in 12.5%, and endoscopic healing in 4.2% of patients after a mean 52.0 (SD 15.0) weeks of therapy. The mean Simple Endoscopic Score in Crohn's disease significantly improved from 23.1 ± 3.7 to 18.0 ± 13.7 after treatment (P = .02). CONCLUSIONS: In the short term, tofacitinib appears well tolerated. The most common adverse event was minor infection. One serious infection and one colorectal cancer occurred. While half of patients reported adverse events, this likely reflects the severe refractory disease in this population and no new safety events were observed. Tofacitinib achieved clinical and endoscopic improvement in some patients with refractory Crohn's disease. Further research is needed to understand the long-term safety and efficacy of tofacitinib in Crohn's disease.

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

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 ±â€…5.2 to 6.5 ±â€…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.

Case Series: Re-induction of Intravenous, Weight-Based Ustekinumab Is Well Tolerated in Patients With Moderate-Severe Crohn's Disease.

Background: Crohn's disease (CD) patients may benefit from biologic optimization. Methods: We retrospectively assessed adverse events (AEs) and clinical/endoscopic response after ustekinumab re-induction in CD patients. Results: We identified 28 patients, all with prior biologic exposure. Eight weeks following re-induction, 10.7% reported ≥1 AE. Three serious AEs occurred in a single patient (CD flares). No infusion reactions occurred. 53.8% and 38.5% achieved clinical response and remission, respectively. 42.8% achieved both endoscopic improvement and remission. Conclusions: Ustekinumab re-induction was well tolerated. Clinical and endoscopic disease activity improved in some patients. Further larger studies are needed to verify these findings in a broader population.

Efficacy of Infliximab in Crohn's Disease Patients with Prior Primary-Nonresponse to Tumor Necrosis Factor Antagonists.

BACKGROUND: Tumor necrosis factor antagonists (TNFs) are effective for moderate-severe Crohn's disease (CD). Approximately one-third of patients have primary-nonresponse to TNFs, which is reported to predict worse response to subsequent TNF therapy. However, this is based on treatment with subcutaneously (SC) administered, fixed-dose TNFs after failure of intravenously (IV) administered, weight-based TNFs. No study has specifically assessed the clinical and endoscopic effectiveness of IV TNFs following primary-nonresponse to SC TNFs. We hypothesize that IV, weight-based TNF dosing offers advantages over SC, fixed-dose TNFs and may be effective despite primary-nonresponse to previous SC fixed-dose TNFs. METHODS: This retrospective cohort study identified patients with moderate-severe CD with primary-nonresponse to one or more SC TNFs who subsequently received the IV TNF, infliximab for ≥ 12 weeks. We described baseline characteristics, and clinical, endoscopic and biochemical response to therapy. RESULTS: Key characteristics of 17 patients are described in Table 1. After ≥ 12 weeks of infliximab, 11 of 15 (73.3%) patients with clinical data reported clinical response and remission. Of 11 patients with endoscopic data, restaging colonoscopy revealed mucosal improvement in seven (63.6%) patients. Of these, five (45.5%) had endoscopic remission and three (27.3%) had mucosal healing. Table 1 Baseline characteristics of CD patients with primary-nonresponse to subcutaneous (SC) tumor necrosis antagonists (TNF), subsequently treated with intravenous (IV) TNF therapy Characteristics N 17 Mean age, years (range) 37.5 (18-67) Mean BMI, kg/m2 (range) 26.6 (17.8-40.6) Mean albumin prior to infliximab, g/dL (range) RR: 3.5-5.2 g/dL 3.57 (2.5-4.2) Female sex [n (%)] 7 (41.2) Tobacco use [n (%)]  Never 15 (88.2)  Former 1 (5.88)  Current 1 (5.88) Age at diagnosis [n (%)]  Less than 17 2 (11.8)  17-40 11 (64.7)  Over 40 4 (23.5) Mean disease duration, yrs (range) 7.76 (1-24) Disease extent [n (%)]  Ileal 2 (11.8)  Colonic 5 (29.4)  Ileocolonic 10 (64.7) Disease behavior [n (%)]  Nonstenosing, nonpenetrating 10 (58.8)  Stenosing 3 (17.6)  Penetrating 2 (11.8)  Stenosing and penetrating 2 (11.8) History of gastrointestinal surgery [n (%)] 4 (23.5)  Ileocecal resection (n) 2  Hemicolectomy (n) 2 Prior therapy [n (%)]  IV corticosteroids 3 (17.6)  Oral corticosteroids 14 (82.4)  5-ASA 12 (70.6)  Thiopurine 14 (82.4)  Methotrexate 10 (58.8) Prior biologic therapy  Adalimumab only 12 (70.6)  Certolizumab pegol only 2 (11.8)  Adalimumab and certolizumab pegol 2 (11.8)  Adalimumab, certolizumab pegol and golimumab 1 (5.88) Dose escalation of prior SC TNF [n (%)]  Adalimumab 9 (52.9)  Certolizumab pegol 0 (0.0)  Golimumab 0 (0.0) During infliximab, concomitant therapy [n (%)]  Immunomodulator 13 (76.5)  Corticosteroid 5 (29.4) CONCLUSIONS: Patients with moderate-severe CD with prior primary-nonresponse to SC, fixed-dose TNFs, subsequently treated with IV, weight-based TNF have high rates of clinical and endoscopic response and remission. Therefore, despite primary-nonresponse to SC TNFs, patients may benefit from IV TNF therapy and may not require a change to a different class of biologic therapy.