An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors.

INTRODUCTION: The use of ustekinumab and vedolizumab as second-line therapies in patients with Crohn's disease (CD) in which tumour necrosis factor alpha inhibitors (TNFi) failed is still debated. The aim of this study was to compare, in a large multicenter observational retrospective cohort, the effectiveness of ustekinumab and vedolizumab as second-line therapies, as assessed by clinical and objective outcomes including endoscopy and gastrointestinal imaging. METHODS: Clinical response, remission, and steroid-free remission at weeks 26 and 52 were evaluated in a retrospective propensity score-weighted and propensity score-matched cohort of patients in which TNFi failed. Objective response and remission were evaluated by 1 or more techniques among endoscopy, magnetic resonance/computed tomography enteroclysis, and small bowel ultrasound. RESULTS: A total of 470 patients with CD (239 treated with ustekinumab and 231 treated with vedolizumab) were included in the study. At week 26, clinical outcomes were similar between the 2 groups. At week 52, clinical remission (ustekinumab 42.5% vs vedolizumab 55.5%, P = 0.01) and steroid-free remission (ustekinumab 40.6% vs vedolizumab 51.1%, P = 0.038) rates were significantly higher in vedolizumab-treated patients. Three hundred two patients (hundred thirty-five treated with ustekinumab and hundred sixty-seven treated with vedolizumab) had an objective evaluation of disease activity at baseline and week 52. At week 52, objective response and remission rates were similar between the 2 groups. Clinical response at week 26 predicted steroid-free remission at week 52 in both ustekinumab-treated and vedolizumab-treated patients. Safety profiles were similar between the 2 groups. DISCUSSION: In patients with CD in which TNFi failed, both ustekinumab and vedolizumab showed similar clinical effectiveness after 26 weeks of treatment. At 1 year, vedolizumab was associated with a higher rate of clinical remission when compared with ustekinumab. However, no difference was observed between the 2 groups when objective outcomes were investigated at this time point.

Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver.

Anti-tumor necrosis factor (TNF)-α agents represent an effective treatment for chronic inflammatory diseases. However, some concerns about their potentially undesirable effects on liver function have been reported. On the other hand, evidence of their therapeutic effects on certain liver diseases is accumulating. Many data showed the safety of anti-TNF-α in patients with chronic hepatitis B and C and in liver transplanted patients even if a strict follow-up and prophylaxis are recommended in well-defined subgroups. On the other side, anti-TNF-α-induced liver injury is not a rare event. However, it is often reversible after anti-TNF-α withdrawal. Anti-TNF-α agents have been tested in advanced stages of severe alcoholic hepatitis and non-alcoholic fatty liver disease. Limited data on the efficacy of anti-TNF-α in patients with autoimmune hepatitis and primary biliary cholangitis are also available. In this review, we explored the hepatic safety concerns in patients receiving anti-TNF-α agents with and without pre-existent hepatic diseases. In addition, the available evidence on their potential benefits in the treatment of specific hepatic diseases is discussed.

Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies.

INTRODUCTION: The therapeutic armamentarium for managing Crohn's disease (CD) has expanded significantly in recent decades. Several biologics with three different mechanisms of action [anti-tumor necrosis factor (TNF)-α, anti-integrin α4ß7, and anti-IL 12/23] are currently available to manage CD. AREA COVERED: This narrative review aims to summarize the most significant efficacy and safety data on the use of infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ) and ustekinumab (UST) for the treatment of CD obtained from studies conducted in the real world (RW), compared to the results of randomized clinical trials (RCTs). EXPERT OPINION: RW studies reported that biologic agents included in this analysis have higher remission rates and lower adverse event rates than findings from RCTs for treating patients with CD. All biological agents have proven effective and safe in RW studies, even when using biosimilars or switching to subcutaneous administration of the molecules for which they are available. Finally, anti-TNF-α agents, particularly IFX, have a higher rate of adverse events (AEs) than VDZ and UST. Therefore, patients at higher risk of AEs may benefit from other biologics than anti-TNF-α. However, further long-term RW studies are needed to confirm these findings.

Impact of a Symbiotic Mixture on Moderate-to-severe Diverticular Disease of the Colon.

BACKGROUND: Microbial imbalance is thought to play a role in the pathogenesis of Diverticular Disease (DD). OBJECTIVE: We aimed to assess the efficacy of a symbiotic mixture (Prolactis GG Plus®) in the treatment of moderate to severe DD, scored according to the Diverticular Inflammation and Complication Assessment (DICA) classification. METHODS: A retrospective study was conducted enrolling the following patients: at the first diagnosis of DD; in whom DD was diagnosed with colonoscopy and scored according to DICA classification; treated with Prolactis GG Plus® two times/daily for 2 consecutive months; in whom the severity of the abdominal pain was scored with a 10-points visual-analogue scale (VAS) at baseline and the end of follow-up; in whom fecal calprotectin (FC) was assessed at baseline and the end of follow-up as µg/g. RESULTS: Twenty-four patients were identified (10 males, 14 females; 16 as DICA 2, and 8 as DICA 3). Prolactis GG Plus® decreased the severity of abdominal pain both in DICA 2 (p =0.02) and DICA 3 patients (p =0.01), while FC decreased significantly in DICA 2 (p <0.02) but not in DICA 3 (p =0.123) patients. Acute diverticulitis occurred during the follow-up in two DICA 3 patients but none DICA 2 patients. Add-on therapy was required by eight DICA 2 (50%) and six DICA 3 patients (75%). CONCLUSION: In newly diagnosed patients with DD, the symbiotic mixture Prolactis GG Plus® can be a potential treatment for moderate (DICA 2) DD as a single treatment.

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms.

Inflammatory bowel diseases, comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of 'real-world' data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

Suboptimal disease control and contributing factors in Italian IBD patients: The IBD-PODCAST Study.

BACKGROUND AND AIM: Suboptimal disease control (SDC) and its contributing factors in IBD according to STRIDE-II criteria is unclear. IBD-PODCAST was a non-interventional, international, multicenter real-world study to assess this. METHODS: Data from the Italian IBD cohort (N=220) are presented here. Participants aged ≥19 with confirmed IBD diagnosis of ≥1 year were consecutively enrolled. A retrospective chart review and cross-sectional assessment by physicians and patients within the past 12 months were performed. SDC or optimal disease control was assessed using adapted STRIDE-II criteria. RESULTS: At the index date, 53.4 % of 116 CD patients and 49.0 % of 104 UC patients had SDC, mainly attributed to a Short Inflammatory Bowel Disease Questionnaire score <50, failure to achieve endoscopic remission, and the presence of active extra-intestinal manifestations in both diseases. Disease monitoring with imaging and/or endoscopy during the previous year was conducted in ∼50 % of patients, with endoscopy performed in ∼40 %. Potential therapeutic adjustments were reported for half of the patients. CONCLUSIONS: This study highlights SDC in a significant portion of IBD Italian patients. These results emphasize the need for more proactive management strategies in both CD and UC patients.

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Insights into Mesalazine Use in Clinical Practice of Young Gastroenterologists.

BACKGROUND: Mesalazine is among the medications most prescribed by gastroenterologists, with variable and controversial use in different settings. We aimed to explore the use of mesalazine in the clinical practice of young gastroenterologists. METHODS: A web-based electronic survey was distributed to all participants of the National Meeting of the Italian Young Gastroenterologist and Endoscopist Association. RESULTS: A total of 101 participants took part in the survey, with a majority (54.4%) being aged >30 years, 63.4% of whom were trainees in academic hospitals, and 69.3% of whom were involved in the clinical management of inflammatory bowel disease (IBD). While both non-dedicated and IBD physicians generally agreed on the appropriate dose of mesalazine for mild ulcerative colitis (UC), significant differences were observed between the two groups for moderate-severe ulcerative colitis (UC). Additionally, in IBD patients who were starting immuno-modulators and/or biologics, 80% of IBD-dedicated physicians continued to prescribe mesalazine, compared to 45.2% of non-dedicated physicians (p = 0.002). Indeed, 48.4% of non-dedicated IBD physicians did not acknowledge mesalazine for colorectal cancer chemoprevention. With regards to Crohn's disease, it is mainly used by 30.1% of IBD physicians for preventing postoperative recurrence of Crohn's disease. Finally, 57.4% used mesalazine for symptomatic uncomplicated diverticular disease, and 84.2% did not recommend its use for irritable bowel syndrome. CONCLUSIONS: This survey showed heterogeneous behaviors in the daily use of mesalazine, mainly in the management of IBD. Educational programs and novel studies are needed to clarify its use.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Adalimumab Biosimilar GP2017 versus Adalimumab Originator in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

The approval of adalimumab (ADA) biosimilars for inflammatory bowel disease (IBD) has reduced the cost of treatment. While several ADA biosimilars are currently available, comparative data on the ADA biosimilar GP2017 (HyrimozTM) and its originator (HumiraTM) in IBD are lacking. We compared the efficacy and safety of GP2017 versus originator in IBD outpatients in an Italian real-life setting. This retrospective analysis enrolled consecutive IBD patients with complete clinical, laboratory, and endoscopic data. Clinical activity was assessed with the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the induction of remission and the safety of GP2017 versus ADA originator. One hundred and thirty-four patients (30.6% with UC and 69.4% with CD, median age 38 years) were enrolled: 62 (46.3%) patients were treated with GP2017, and 72 (53.7%) with ADA originator; 118 (88.1%) patients were naïve to ADA. Clinical remission was obtained in 105 (78.4%) patients, during a median follow-up of 12 months, 82.3% and 75% in the GP2017 and ADA originator groups, respectively (p = 0.311). Treatment was well tolerated in both groups. This analysis of real-world data suggests that GP2017 and its originator are equivalent in terms of efficacy and safety in patients with IBD.

Clinical and epidemiological features of ulcerative colitis patients in Sardinia, Italy: Results from a multicenter study.

BACKGROUND: There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden. AIM: To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy. METHODS: We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit. RESULTS: Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy. CONCLUSION: Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

Impact of SARS-CoV-2 Infection on the Course of Inflammatory Bowel Disease in Patients Treated with Biological Therapeutic Agents: A Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns in patients with inflammatory bowel disease (IBD), not only due to consequences of coronavirus disease 2019 itself but also as a possible cause of IBD relapse. The main objective of this study was to assess the role of SARS-CoV-2 in IBD clinical recurrence in a cohort of patients undergoing biological therapy. Second, we evaluated the difference in C-reactive protein (CRP) levels between the start and end of the follow-up period (ΔCRP) and the rate of biological therapy discontinuation. Patients with IBD positive for SARS-CoV-2 infection were compared with non-infected patients. IBD recurrence was defined as the need for intensification of current therapy. We enrolled 95 IBD patients with SARS-CoV-2 infection and 190 non-infected patients. During follow-up, 11 of 95 (11.6%) SARS-CoV-2-infected patients experienced disease recurrence compared to 21 of 190 (11.3%) in the control group (p = 0.894). Forty-six (48.4%) SARS-CoV-2-infected patients discontinued biological therapy versus seven (3.7%) in the control group (p < 0.01). In the multivariate analysis, biological agent discontinuation (p = 0.033) and ΔCRP (p = 0.017), but not SARS-CoV-2 infection (p = 0.298), were associated with IBD recurrence. SARS-CoV-2 infection was not associated with increased IBD recurrence rates in this cohort of patients treated with biological agents.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Review article: safety of new biologic agents for inflammatory bowel disease in the liver.

New biologic agents (vedolizumab, ustekinumab and tofacitinib) represent an effective treatment for inflammatory bowel diseases and have been recently approved. However, with a rapidly evolving complement of advanced targeted therapies, new concerns about their potentially undesirable effects on liver function emerge. In particular, little is known about safety data in patients with hepatitis B virus, hepatitis C virus chronic infections, cirrhosis and in transplanted patients who are accumulating. In addition, these new agents have also been associated with drug-induced liver injury. Limited data on the efficacy of vedolizumab in patients with primary sclerosing cholangitis are also available. This article reviews available data about hepatic safety concerns in patients receiving vedolizumab, ustekinumab and tofacitinib with and without preexistent hepatic diseases.

Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study.

BACKGROUND: The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. OBJECTIVE: The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. METHODS: This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. RESULTS: From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21-85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2-0.8), while previous exposure to antitumour necrosis factor-α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5-5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%). CONCLUSIONS: Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to antitumour necrosis factor-α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab.

BACKGROUND AND AIMS: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. METHODS: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. RESULTS: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. CONCLUSIONS: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.