Safety and effectiveness of tofacitinib in ulcerative colitis: Data from TOFA-UC, a SN-IBD study.

BACKGROUND: Real-world evidence is needed to determine the value of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC). AIM: To assess the safety and effectiveness of TOFA in clinical practice. METHODS: TOFA-UC is a multicenter, observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with UC starting TOFA from its introduction in Sicily (July 2021) to July 2022 were included. RESULTS: 111 patients were included (mean follow-up: 31.7 ± 14.9 weeks; biologic-experienced: 92.8%). Nineteen adverse events were reported (17.1%; incidence rate: 28.2 per 100 patient years), including 11 cases of hypercholesterolemia and 3 infections (no cases of herpes zoster reactivation. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient years). Twenty-six patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs, and 23 to non response or loss of response. CONCLUSIONS: TOFA is safe and effective in patients with UC, including those with history of multiple failures to biological therapies.

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIM: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection. RESULTS: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy. CONCLUSIONS: Ustekinumab could be a promising option for the treatment of POR of CD.

Severe Activity of Inflammatory Bowel Disease is a Risk Factor for Severe COVID-19.

BACKGROUND: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids. METHODS: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes. RESULTS: Data on 122 patients (mean age, 43.9 ±â€…16.7 years; males, 50.0%; Crohn's disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006-1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104-164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320-178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076). CONCLUSIONS: In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19.

This retrospective, observational study on patients with inflammatory bowel disease and severe acute respiratory syndrome coronavirus 2 infection showed that severe inflammatory bowel disease activity was the only independent risk factor for severe coronavirus disease 2019.

Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown. AIMS: To assess the effectiveness of VDZ in this setting. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up. RESULTS: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%). CONCLUSIONS: VDZ may be an effective option for the treatment of postoperative recurrence of CD.

SPOSAB ABP 501: A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501.

BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Ustekinumab in Crohn's disease: Real-world outcomes from the Sicilian network for inflammatory bowel diseases.

BACKGROUND AND AIM: Ustekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real-life data are scarce, so the aim of this study was to assess the effectiveness and safety of ustekinumab in an Italian cohort of CD patients. METHODS: Data of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end-points were steroid-free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C-reactive protein. Secondary end-points were treatment response, treatment persistence at 12 months, and safety. RESULTS: A total of 131 patients (males 56%; mean age 46 years ±15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid-free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow-up, there was a significant reduction of steroid use (P = 0.012) and of the Harvey-Bradshaw Index (P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age. CONCLUSIONS: Data from our real-life cohort of treatment-refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab.

Effectiveness of Ustekinumab on Crohn's Disease Associated Spondyloarthropathy: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND: The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown. RESEARCH DESIGN AND METHODS: All consecutive CD patients with active SpA at the initiation of the treatment with UST were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was the articular response at 8 and 24 weeks, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. RESULTS: Thirty CD patients with active SpA at the initiation of the treatment with UST were assessed. At 24 weeks, 13 patients (43.3%) had an articular response, including 10/18 patients (55.5%) with peripheral SpA and 3/9 patients (33.3%) with axial and peripheral SpA. No patient with axial SpA experienced an articular response. The drop of mean as Harvey-Bradshaw Index values from baseline to week 24 was higher in patients with articular response compared with non-responders (3.8 ± 2.4 vs. 1.3 ± 2.8, p = 0.02). CONCLUSIONS: Our real-world, multicentre experience showed that UST was able to obtain a response on articular symptoms in nearly half of the patients with CD and active SpA after 24 weeks of treatment.

A propensity score weighted comparison of Vedolizumab, Adalimumab, and Golimumab in patients with ulcerative colitis.

BACKGROUND: No real-life study on the comparative effectiveness of Vedolizumab (VDZ), Adalimumab (ADA), and Golimumab (GOL) in ulcerative colitis (UC) is currently available. AIMS: To compare the effectiveness of the three biologics in consecutive patients with UC. METHODS: A three-arms propensity score-adjusted analysis was performed using the Inverse Probability of Treatment Weighting method. RESULTS: 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included (median follow-up: 47.6 weeks). At 12 weeks (n = 463), a steroid-free remission was reported in 24.1% patients in the VDZ group, in 33.3% patients in the ADA group, and in 30.6% patients in the GOL group (p = n.s. for all comparisons). At 52 weeks (n = 377), a steroid-free remission was reported in 51.5% patients in the VDZ group, in 31.2% patients in the ADA group, and in 29.4% patients in the GOL group (p = 0.002 for VDZ vs. ADA, p = 0.001 for VDZ vs. GOL, p = n.s. for ADA vs. GOL). Cox survival analysis demonstrated that patients treated with VDZ had reduced probability of treatment discontinuation compared to those treated with ADA (HR: 0.42, 95% CI 0.28-0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19-0.46, p < 0.001), while patients treated with ADA had reduced risk of treatment discontinuation compared to those treated with GOL (HR: 0.71, 95% CI 0.50-1.00, p = 0.048). CONCLUSIONS: VDZ was superior to ADA and GOL at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared to GOL.

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. RESULTS: We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60-80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18-59 years; 57 males). Older patients with Crohn's disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. CONCLUSION: Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. RESULTS: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.

A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients With Crohn's Disease: Real-Life Data From the Sicilian Network for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. METHODS: Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naïve and non-naïve patients. RESULTS: A total of 632 patients [735 total treatments] were included. Among naïve patients, a clinical benefit [the sum of steroid-free remission plus clinical response] was achieved in 81.8% patients treated with ADA and in 77.6% patients treated with IFX (adjusted odds ratio [OR]: 1.23, 95% CI 0.63-2-44, p = 0.547] at 12 weeks; after 1 year, a clinical benefit was achieved in 69.2% of patients treated with ADA and in 64.5% patients treated with IFX [adjusted OR: 1.10, 95% CI 0.61-1.96, p = 0.766]. Among non-naïve patients, a clinical benefit was achieved in 61.7% of patients treated with ADA and in 68.1% of patients treated with IFX [adjusted OR: 0.72, 95% CI 0.21-2.44, p = 0.600] at 12 weeks; after 1 year, a clinical benefit was achieved in 48.9% of patients treated with ADA and in 40.4% patients treated with IFX [adjusted OR: 1.23, 95% CI 0.54-2.86, p = 0.620]. CONCLUSIONS: In this propensity score-matched comparison of ADA and IFX in CD, both drugs showed high rates of clinical benefit, without significant differences between them.

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis.

BACKGROUND: Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. AIMS: We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. METHODS: 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. RESULTS: Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in golimumab patients (p = 0.008) at the end of follow up. These data were confirmed by propensity score analysis. A further analysis considering adalimumab optimization as treatment failure showed that the difference between adalimumab and golimumab was not significant. CONCLUSION: Adalimumab and golimumab are effective in the treatment of ulcerative colitis. Adalimumab seems to be more effective than golimumab. This difference is probably affected by the impossibility of golimumab to be optimized in Italy while adalimumab is.

The real-world effectiveness of vedolizumab on intestinal and articular outcomes in inflammatory bowel diseases.

BACKGROUND: The effectiveness of vedolizumab in real-world practice is under evaluation, while its role in inflammatory bowel disease-associated spondyloarthritis is still unclear. AIMS: To report real-world data about the effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22 weeks of treatment. METHODS: Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a prospective multicentre observational study. RESULTS: 163 patients (84 with Crohn's disease and 79 with ulcerative colitis) were included. At week 10, a steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a steroid-free remission was obtained in 40.8% of patients. A response on articular symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%) patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%) patients at week 22. The only factor associated with articular response was the coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, p = 0.05; at week 22: OR 5.600, p = 0.08). CONCLUSIONS: Vedolizumab showed good effectiveness after 10 and 22 weeks of treatment. A subset of patients reported improvement also on articular symptoms, probably as a consequence of the concomitant control of gut inflammation.