ABSTRACT
Background and aim: Dual Targeted Therapy (DTT) is a novel therapeutic strategy proposed for the management of patients with complex inflammatory bowel disease (IBD). Our aim was to evaluate the safety and effectiveness of this approach in a real-life setting Materials and methods: In this single centre retrospective cohort study, we collected data on IBD patients receiving DTT from 2017 to 2022. Baseline characteristics, clinical activity of intestinal and extraintestinal disease, C-reactive protein (CRP) levels, endoscopic assessment and adverse events (AEs) were recorded. Clinical remission, CRP normalization, endoscopic remission and occurrence of AEs were investigated at baseline and during follow up Results: Sixteen patients were identified;indications for DTT were: uncontrolled IBD (11 patients), uncontrolled extraintestinal manifestations (EIMs) (6 patients: 4 spondyloarthritis, 2 psoriatic disease). Patients received vedolizumab (VDZ, 14, 87.5%), ustekinumab (UST, 8, 50%), anti-TNFα (7, 43.8%), sekukinumab (2, 12.5%), tofacitinib (1, 6.3%). The most common combinations were: VDZ+UST (6 patients, 37.5%) and adalimumab+VDZ (3, 18.8%). At baseline, 15/16 (93.8%) and 4/6 (66.6%) patients had active intestinal and EI symptoms, respectively;14 (87.5%) patients had positive CRP and 5 (31.3%) were receiving oral steroids. Median follow-up duration on DTT was 15 months (IQR 11-22). Clinical intestinal remission was reported by 6/16 (37.5%) and 3/11 (27.3%) patients at 6 and 12 months, respectively. Clinical remission of EIMs was reported by 3/7 (42.9%) at 6 and 5/7 (71.4%) patients at 12 months, respectively. CRP normalization was observed in 3/16 (18.8%) and 6/11 (54.5%) patients at 6 and 12 months, respectively. 80% of patients on steroid therapy at baseline discontinued them within 6 months. Endoscopic assessments were available for 8 patients, with endoscopic remission in 2, endoscopic improvement in 3 and no improvement in 3. Four patients (25%) experienced an AE (1 COVID-19 and reactivation of perianal disease;1 mild pneumonitis and reactivation of perianal disease;1 drug-induced pneumonitis;1 arthralgia and COVID-19). Finally, 1 patient underwent colectomy due to uncontrolled disease. Three patients discontinued DTT: 2 because of treatment failure, 1 because of an AE (drug-induced pneumonitis) Conclusions: DTT can be considered a reasonably safe and effective treatment in complex IBD patients, either with uncontrolled intestinal inflammation or with concomitant EIMs, when other therapeutic options have failed
ABSTRACT
Background: In the last year, the severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has spread rapidly around the world. The interactions between SARS-CoV-2 and inflammatory bowel disease (IBD) are so far not fully understood. In particular, no studies evaluated the potential role of SARS-CoV-2 on IBD course. Indeed, it is known that viral infections can be act as triggers for IBD flare and it is reasonable that the possible drug discontinuation during SARS-CoV-2 infection could in turn lead to an IBD flare. Methods: This was a prospective, observational case-control study. From March 11th 2020 to June 30th 2020 we enrolled IBD patients with proven SARS-Cov-2 infection (cases) and IBD patients without SARS-CoV-2 infection matched for sex, age, diagnosis, therapy and clinical activity (controls). Cases and controls were followed-up at least for 6 months. Differences between case and control group were tested for significance using the Students t test and Fishers test, as appropriate. A two-tailed p value < 0.05 was indicative of statistical significance. Results: 219 IBD patients (127 UC, 58.0%) with SARS-CoV-2 infection and 219 IBD patients without SARS-CoV-2 infection were enrolled. Table 1 shows baseline features of the population. Among the 122 cases in clinical remission at the time of viral infection, 28 (22.9%) showed a disease flare;this percentage was significantly higher than that observed in controls: 12/137 (8.8%)(p=0.0018). Among patients with disease flare, there were no significant differences between cases and controls group in terms of age (42.3 ± 16.0 vs. 43.1 ± 15.4 years, p=0.44), gender (female 45.7% vs. 48.2%, p= 0.54), use of biologic therapies (p=0.83) and UC or CD diagnosis (p=0.06). Biologic therapy was temporary withdrawn more significantly in cases than in controls (68/202, 33.6% vs. 14/204, 6.9%) (p<0.001) and overall biologic therapy discontinuation was significantly associated with disease flare (OR 2.56, 95% CI 1.026.41, p=0.04). Conclusion: IBD patients with SARS-CoV-2 infection have an increased risk to have a clinical recurrence in short-term in comparison with IBD patients without SARS-CoV-2 infection. This increased risk could be due to the viral infection and/or to the temporary discontinuation of biologic therapies, because of infection.