Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Tuberculous chemoprophylaxis requirements and safety in inflammatory bowel disease patients prior to anti-TNF therapy.

BACKGROUND: Preventive actions are advised since the use of anti-tumor necrosis factor (TNF) agents is known to increase the risk of tuberculosis (TB). No data related to the effectiveness and safety of the preventive chemoprophylaxis (ChP) for TB in inflammatory bowel disease (IBD) patients are available. The goal was to evaluate the requirements, effectiveness, and safety profile of ChP in IBD patient candidates for anti-TNF therapy. METHODS: All IBD patients diagnosed with latent TB while evaluated for anti-TNF therapy from the IBD database of 9 Spanish centers were included. Epidemiological and clinical data, risk factors for hepatotoxicity, ChP regimens, and side effects were registered. RESULTS: Sixty-three out of 497 IBD evaluated patients (12.5%) had latent TB. Sixty-eight percent were on immunomodulators and 42% on systemic corticosteroids when a TB skin test (TST) was performed. The detection of a positive TST was done in 86% after a single exposure, but 14% needed a booster. All but 1 were treated with isoniazid alone for 6 or 9 months, and only 1 case required ChP discontinuation because of hepatotoxicity. No risk factors for hepatotoxicity were found. No cases of active TB were noticed in the 67 patients further treated with anti-TNF therapy. CONCLUSIONS: More than 10% of Spanish IBD patients who are candidates for anti-TNF therapy have latent TB. TST retest is required to identify at least 14% of such patients; therefore, it should be considered if the initial TST is negative. ChP is safe in IBD patients even in those taking concomitant, potentially hepatotoxic drugs.