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Background No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. Methods The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. Results Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). Conclusions The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

Background There is no head-to-head trial comparing ustekinumab (UST) and vedolizumab (VDZ) in Crohn’s disease (CD). Recently, real-world studies evaluated the two biologics in patients refractory to anti-TNF therapy, i.e. as second-line agents. Conversely, no study specifically focused on the effectiveness of UST and VDZ as third-line agents, i.e. after failure with at least one TNF-α inhibitor plus failure with VDZ or UST. We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ in these highly-refractory patients with CD. Methods Data of consecutive patients with CD treated with UST and VDZ as third-line therapy until October, 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The effectiveness was evaluated at, 8, 26, and, 52 weeks, and as treatment persistence at the end of follow up. The clinical outcomes were steroid-free clinical remission (SFCR - Harvey-Bradshaw Index Results 143 patients (UST: n=113; VDZ: n=30) were included. After, 8 weeks, SFCR was reported in, 38.1% of patients treated with UST and in, 43.3% of patients treated with VDZ (p=0.75), while CR was reported in, 61.9% of patients treated with UST and in, 60.0% patients treated with VDZ (p=1.00). After, 26 weeks, the rates of SFCR and CR were, 41.6% for UST and, 50.0% for VDZ (p=0.60), and, 61.4% for UST and, 66.7% for VDZ (p=0.81), respectively. After, 52 weeks, the rates of SFCR and CR were, 51.8% for UST and, 57.1% for VDZ (p=0.78), and, 65.9% for UST and, 71.4% for VDZ (p=0.77), respectively. Lack of difference in effectiveness between the two drugs at any time point was confirmed by multiple logistic regression models. After, 26 weeks, 88.7% of patients treated with UST and, 81.4% of patients treated with VDZ were still on treatment. Univariable Cox survival analysis showed a higher probability of treatment discontinuation for VDZ compared with UST (HR for VDZ:, 2.66; p=0.008), even if such difference was not confirmed at the multiple Cox proportional hazard regression model (HR for VDZ:, 1.94; p=0.08), where only age (HR, 0.98; p=0.04) and use of systemic steroids at baseline (HR, 3.29; p=0.003) were found to be independent predictors of treatment discontinuation. Conclusion This is the first real-world study assessing VDZ and UST as third-line therapy in patients with CD. Both drugs showed surprisingly high effectiveness, without significant differences between them.

Background Clinical data on the use of Adalimumab (ADA) biosimilar ABP 501 in inflammatory bowel disease (IBD) are lacking. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) treated with ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled. Patients were divided into 3 groups (group A: naive to ADA and naive to anti-TNFs; group B: naive to ADA and previously exposed to anti-TNFs; group C: switch from ADA originator to ABP 501). The primary end-point was the assessment of safety, in terms of rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of clinical response and steroid-free clinical remission at 12 weeks for group A and B, and as treatment persistency for all 3 groups. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included [group A: 189 (33.8%); group B: 30 (5.4%); group C: 340 (60.8]. Overall, the mean follow-up was 8.7 months (median 10.0 months, interquartile range: 6.0–12.0 months), and the total follow-up time was 403.4 patient-years. 36 SAEs occurred in 36 patients (6.4%), with an incidence rate of 8.9 per 100 person-years (PY), and 22 of them caused the withdrawal of the drug (incidence rate: 5.5 per 100 PY). The incidence rate of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; incidence rate ratio=3.61; p Conclusion This is the first prospective study on the use of ADA biosimilar ABP 501 in IBD. 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.

Background The efficacy of Ustekinumab (UST) on Crohn’s disease (CD) associated spondyloarthropathy (SpA) was evaluated neither in randomized controlled trials nor in real-world studies. Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a multicentre, real-world assessment of the effectiveness of UST on CD-associated SpA Methods All consecutive CD patients with active SpA at the initiation of the treatment with UST from January 2019 (the date on which the drug became available for clinical practice in Sicily) to August 2019 were extracted from the SN-IBD cohort. The study outcomes were evaluated at 8 and 24 weeks. The primary outcome was the articular response, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. As ancillary end-points, the clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline with a concomitant reduction of at least ≥ 50% of steroid dosage compared with baseline) and the steroid-free remission (Harvey-Bradshaw Index < 5 without steroids use) were assessed. Results Out of 131 total patients treated with UST, 30 consecutive patients (22.9%) had active SpA at baseline (axial SpA: 3/30; peripheral SpA: 18/30; axial plus peripheral SpA: 9/30). After 8 weeks, 10 patients (33.3%) reported an articular response [0/3 patients with axial SpA, 7/18 patients (38.9%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. After 24 weeks, 13 patients (43.3%) had an articular response [0/3 patients with axial SpA, 10/18 patients (55.5%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. None of these 13 responders was taking systemic steroids at 24 weeks. The concomitant presence of a clinical response on intestinal symptoms was associated with the articular response at 24 weeks at univariable analysis (OR 5.14, CI 1.09-32.70, p=0.038). Conclusion UST obtained a response on articular symptoms in nearly half of the patients with CD and active SpA at baseline after 24 weeks. The rate of response was higher in case of peripheral arthropathy. The articular response was associated with the clinical response on intestinal symptoms.

Background The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown. We aimed to assess the effectiveness of VDZ in this setting. Methods All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence 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. In patients with Rutgeerts score i0 or i1 at baseline, endoscopic success was defined by maintenance of Rutgeerts score i0 or i1; in patients with Rutgeerts score ≥ i2 at baseline, it was 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 Seventy patients were included (median follow-up: 23.5 months). All 9 patients without endoscopic recurrence at baseline (Rutgeerts score i0 or i1) and available post-treatment colonoscopy maintained a Rutgeerts score i0 or i1 (treatment success: 100%). In patients with endoscopic recurrence (Rutgeerts score ≥ i2 at baseline), a reduction of at least one point in the Rutgeerts score was obtained in 20 out of 42 patients (47.6%). By combining the two subgroups, the overall endoscopic success was achieved in 29 out of 51 patients (56.9%). Furthermore, 14 out of 42 patients (33.3%) with endoscopic recurrence at baseline achieved a Rutgeerts score i0 or i1 at the subsequent colonoscopy. Clinical failure was reported in 13/70 patients (18.6%) at one year, and in 23/70 patients (32.9%) at the end of follow-up. A new resection was required in 7/70 patients (10.0%). Conclusion VDZ may be a therapeutic option for the management of postoperative recurrence of CD. Further studies are needed to confirm these results.

Background Biologic-naïve patients treated with Vedolizumab (VDZ) are largely underrepresented in real-world cohorts. We performed a multicentre, observational, cohort study on the effectiveness and safety of VDZ as treatment for Crohn’s disease (CD) and ulcerative colitis (UC) among biologic-naïve subjects. Methods Data of consecutive biologic-naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The primary outcome was the clinical response at 14 and 52 weeks evaluated with Harvey Bradshaw Index in CD and partial Mayo score in UC. Results 172 consecutive patients (CD: n=88; UC: n=84; median age 66.0 years) were included, with a median follow-up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid-free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid-free remission. All differences between CD and UC were not statistically significant. Cox survival analysis showed no significant difference in the probability of treatment discontinuation between CD and UC patients (log-rank p=0.73). Conclusion This large, real-world, multicenter study demonstrated the effectiveness and safety of VDZ as a first-line biologic, showing high rates of clinical response and steroid-free remission at both induction and maintenance.

Background and Aims There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive patients treated with ADA biosimilar ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled to assess its safety and effectiveness. Patients were divided into 3 groups: group A, naïve to ADA and naïve to anti-TNFs; group B, naïve to ADA, previously exposed to anti-TNFs; group C: switched from ADA originator to ABP 501. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six SAEs occurred in 36 patients [(6.4% - incidence rate (IR): 8.9 per 100 person-years (PY)]. The IR of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; IR ratio=3.61; p 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.

Background No real-life study aiming at comparing at the same time the effectiveness of vedolizumab (VDZ), adalimumab (ADA), and golimumab (GOL) in Ulcerative colitis (UC) is currently available. Methods Data of consecutive patients with UC treated with VDZ, ADA, and GOL from June 2015 to December 2018 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A three-arms propensity score-adjusted analysis was performed to reduce bias caused by imbalanced covariates at baseline, including the proportion of TNF-α inhibitor naïve and non-naïve patients, using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 8 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (partial Mayo score Results A total of 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included, with a median follow-up of 47.6 weeks (IQR 20.0–85.9). At 8 weeks, a clinical benefit was achieved in 70.6% patients treated with VDZ, in 68.5% patients treated with ADA, and in 67.6% patients treated with GOL (p = n.s. for all comparisons). After 52 weeks, VDZ showed better rates of clinical benefit compared with both ADA (71.6% vs. 47.5; OR: 2.79, 95% CI 1.63–4.79, p < 0.001) and GOL (71.6% vs. 40.2%; OR: 3.77, 95% CI 2.08–6.80, p < 0.001), while the difference between ADA and GOL was not significant. Cox survival analysis demonstrated that patients treated with VDZ had a reduced probability of treatment discontinuation compared with 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 a reduced risk of treatment discontinuation compared with those treated with GOL (HR: 0.71, 95% CI 0.50–1.00, p = 0.048). Post-treatment mucosal healing rates showed a numerical but non-significant difference in favour of VDZ (48.1%) compared with ADA and GOL (38.0% and 34.6%, respectively). Conclusion In the first study comparing at the same time the clinical effectiveness of VDZ, ADA, and GOL in UC patients via propensity score-adjusted analysis, VDZ was superior to both subcutaneous agents at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared with GOL.

Background Few data on Infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. Methods SPOSIB SB2 is a multicentre, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s disease (CD) or Ulcerative Colitis (UC) starting IFX biosimilar SB2 from the introduction of the drug in Sicily (March 2018) to September 2019 (18 months) were enrolled. Patients were divided into five groups (group A: naive to IFX, naive to anti-TNFs; group B: naive to IFX, previously exposed to other anti-TNFs; group C: switch from IFX originator to SB2; group D: switch from CT-P13 to SB2; group E: multiple switches: from IFX originator to CT-P13 to SB2). The primary end-point was the assessment of safety, in terms of the rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of steroid-free clinical remission and clinical response at 8 weeks and at the end of follow-up, and as treatment persistency. Results 276 patients (median age 39 years; CD 49.3%, UC 50.7%) were included [group A: 127 (46.0%); group B: 65 (23.6%); group C: 17 (6.2%); group D: 43 (15.6%); group E: 24 (8.7%)]. The cumulative number of infusions of SB2 was 1798, the median follow-up was 8 months (IQR: 4–12 months), and the total follow-up time was 182.7 patient-years (PY). Sixty-seven SAEs occurred in 57 patients (20.7%), with an incidence rate of 36.7 per 100 PY, and 26 of them caused the withdrawal of the drug. The incidence rate ratio (IRR) of SAEs was higher among patients in group B compared with group A (57.7 vs. 30.2 per 100 PY; IRr = 1.91; p = 0.026) and group C (57.7 vs. 18.9 per 100 PY; IRr = 2.93; p = 0.045). The effectiveness of IFX biosimilar SB2 after 8 weeks of treatment was evaluated in patients naïve to IFX (group A + B; n = 192): 110 patients (57.3%) had steroid-free remission, 26 patients (13.5%) achieved a partial response, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank p = 0.15). Conclusion This is the first prospective study on the use of IFX biosimilar SB2 in IBD. Safety and efficacy of SB2 seem to be overall similar to those reported for IFX originator and IFX biosimilar CT-P13. A higher incidence of SAEs was observed among patients naive to IFX and previously exposed to other anti-TNFs.

Background Currently, there are no randomised controlled trials focussing on direct comparisons between biologics in Crohn’s disease (CD), while there is an unmet need to better understand and compare the effectiveness of these drugs. We performed a multicentre, real-life, comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD. Methods Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A propensity score analysis was performed using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 12 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (Harvey–Bradshaw Index < 5 without steroid use) and clinical response (reduction of the Harvey–Bradshaw Index ≥ 3 points with a concomitant decrease of steroid dosage compared with baseline). The sum of the two outcomes was defined as a clinical benefit. The achievement of endoscopic response (a reduction of Simple Endoscopic Score for CD ≥ 50% compared with baseline) or mucosal healing (Simple Endoscopic Score for CD ≤ 2) was assessed after at least 6 months of treatment. Results A total of 585 treatments (VDZ: n = 277; ADA: n = 308) were included, with a median follow-up of 56.0 weeks (IQR 24.0–104.0). After 12 weeks, a clinical benefit was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (p = 0.11 in propensity score analysis), while at 52 weeks a clinical benefit was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (p = 0.33 in propensity score analysis). The median treatment persistences for VDZ and ADA were 52 weeks and 64 weeks, respectively. Cox survival analysis weighted for IPTW showed no significant difference in the probability of treatment discontinuation between the two drugs (HR for VDZ=1.20; p = 0.34). Post-treatment endoscopic response and mucosal healing rates were similar between the two drugs (endoscopic response: 35.3% for VDZ and 25.5% for ADA, p = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, p = 0.85). Conclusion This is the first real-life study comparing VDZ and ADA in CD patients via propensity score-adjusted analysis. Even if crude rates of all clinical outcomes were higher for ADA compared with VDZ, such differences were not significant when patients’ characteristics at baseline were weighted by propensity score.

Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP). Results One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p < 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1). Conclusion Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.