Predictors of Efficacy of Janus Kinase Inhibitors in Patients Affected by Ulcerative Colitis.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC.

Transition from intravenous to subcutaneous biological therapies in inflammatory bowel disease: An online survey of patients.

BACKGROUND: The transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options. METHODS: We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded. RESULTS: Four hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced. CONCLUSION: The transition from in-hospital to subcutaneous therapeutic management of biological therapy at home was generally viewed favorably by patients, especially if they have commitments or were residents far from the IBD center.

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.

BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.

Effectiveness and Safety of Switching from Intravenous to Subcutaneous Vedolizumab Formulation in Inflammatory Bowel Disease Patients in Clinical Remission.

BACKGROUND AND AIMS: Subcutaneous vedolizumab formulation has been shown to be as effective and safe as the intravenous one in randomized control trials. Real-life data are limited especially for patients receiving long-term intravenous therapy. This study aimed to evaluate the safety and effectiveness of switching from intravenous to subcutaneous vedolizumab in a large cohort of patients with stable clinical remission. METHODS: In this prospective cohort study, we enrolled consecutive patients attending our center between September 2021 and April 2022. The baseline demographic characteristics, 12- and 24-weeks follow-up clinical activity, C-reactive protein levels, and adverse events were recorded. The primary endpoint was to assess combined steroid-free clinical remission plus biochemical remission 24-week after the switch. RESULTS: 93 patients (43 Crohn's disease, 50 ulcerative colitis), switched to subcutaneous vedolizumab after a median duration of intravenous treatment of 36 months [IQR 16-52]. At baseline, 80 patients (86%) had a combined remission. At 24-week, 89.2% (n=74) maintained combined steroid-free clinical remission plus biochemical remission. 25 adverse events were reported, mostly SARS-CoV-2 infections and injection site reactions, with a further four recurrence episodes. Twelve patients (12.9%) discontinued subcutaneous administration and restarted intravenous vedolizumab. CONCLUSIONS: Switching from intravenous to subcutaneous vedolizumab can be considered effective and safe for maintaining remission in patients with inflammatory bowel disease. In addition, this might reduce healthcare costs. However, large-scale real-life studies with long-term follow-up are necessary.

Patient-Reported Outcomes for the Assessment of Sexual Health Among Patients Affected by Inflammatory Bowel Disease.

Patients affected by inflammatory bowel disease (IBD) frequently report impaired quality of sexual life and complain of sexual dysfunctions. Both disease-specific features and psychological factors can be held responsible for these conditions. However, sexuality and all matters relating to sexual health are often wrongfully considered unrelated to IBD and, therefore, overlooked during medical visits. To overcome these difficulties and to best assess patients' perceptions about their sexual health status, the use of patient-reported outcomes (PROs) could represent a valid strategy. In real-world studies, several non-IBD specific questionnaires, exploring different domains of sexuality, have been applied and validated for the IBD population. This review summarizes the available evidence on sexual health among IBD patients and the data supporting the application of PROs to screen the quality of sexual life, as well as the rate and types of sexual dysfunctions, among IBD patients.

Targeting IL12/23 in ulcerative colitis: update on the role of ustekinumab.

As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline. Interleukin (IL)-12 and IL23 are two key cytokines responsible for promoting and perpetuating bowel inflammation in IBD. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of both cytokines, and it was recently approved for the treatment of ulcerative colitis (UC). In the pivotal phase III UNIFI trial, ustekinumab showed a superiority over placebo in both clinical and endoscopic outcomes; furthermore, it was characterized by a favorable safety profile, with a similar rate of adverse events as compared with placebo. Recent evidence from real-life experiences have started accumulating, generally confirming the effectiveness and safety figures emerged from the registration studies. However, most of these observational studies enrolled multirefractory patients; moreover, comparative data with other target therapies are lacking, leaving physicians without clear indications about the appropriate positioning of ustekinumab in the therapeutic pipeline for UC. This review examines the basis of targeting IL12-23 in UC therapy and summarizes the data from both clinical trials and real-life studies, to highlight the main evidence already available and the research gaps that need to be filled for the optimal usage of ustekinumab in UC.

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.

Infectious risk of vedolizumab compared with other biological agents in the treatment of inflammatory bowel disease.

BACKGROUND AND AIMS: Vedolizumab is a gut-selective anti-integrin (α4ß7) antibody for the treatment of inflammatory bowel disease with a well-known optimal safety profile. We aimed to compare its risk of infections with that of anti-TNF drugs and ustekinumab in patients with both ulcerative colitis and Crohn's disease. METHODS: All Crohn's disease and ulcerative colitis patients undergoing biological treatment at our centre between 2013 and 2019 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of the exposure-adjusted infection rates of vedolizumab, anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs). RESULTS: The overall exposure-adjusted infection rate was 11.5/100 PYs. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations and gut infections. The rate of serious infections was 1.3/100 PYs. The infection rate of vedolizumab was 17.5/100 PYs, with Crohn's disease patients having a lower infection risk compared with ulcerative colitis patients (P = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the vedolizumab group (P = 0.0001). CONCLUSIONS: Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with ulcerative colitis have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this is due to the gut-selective mechanism of action of vedolizumab.

Stevens-Johnson Syndrome and Herpes Simplex Type 1 Infection during Adalimumab Therapy for Crohn's Disease.

Stevens-Johnson syndrome (SJS) is a severe mucocutaneous adverse drug reaction with a relatively high mortality rate. SJS is described during herpes simplex virus type 1 (HSV1) infection and, rarely, even during adalimumab therapy. We report the case of a patient with Crohn's disease who developed SJS during an HSV1 infection and a contemporaneous anti-TNFα therapy with adalimumab. Remission was achieved with suspension of adalimumab and high doses of intravenous steroids and antivirals. Patients with HSV1 infection and on adalimumab therapy have a combined risk of SJS and should be monitored closely.

Increased Risk of Liver Cirrhosis during Azathioprine Therapy for Crohn's Disease.

Azathioprine is a cornerstone of the therapy of Crohn's disease. Unfortunately, infections and malignancies are relatively common adverse effects related to this drug; however, cirrhosis is exceptionally reported as a side effect. We report the case of a 49-year-old male patient with ileocolonic steno-penetrating Crohn's disease who developed hepatic cirrhosis while treated with azathioprine. After taking azathioprine for 3 years with regular follow-up, he developed pancytopenia, and liver cirrhosis was diagnosed with ultrasound, abdomen computed tomography scan, transient elastography, and liver biopsy. As all other causes of liver damage were excluded, azathioprine was believed to be the cause of liver injury and therefore was interrupted.

Neonatal outcomes in pregnancies after bariatric surgery: a retrospective multi-centric cohort study in three French referral centers.

OBJECTIVE: To analyze short-term neonatal outcomes in pregnancies after bariatric surgery according to procedure, to the body mass index (BMI) at the beginning of the pregnancy and to the interval from surgery to conception, using a retrospective multi-centric cohort study in three French tertiary perinatal care and bariatric centers. METHODS: 94 neonates in 79 women were included. Frequencies of adverse neonatal events by procedure, laparoscopic adjustable gastric banding (LAGB, n = 63) or Roux-en-Y gastric bypass (RYGB, n = 31), BMI class (72 women with BMI ≥ 30 kg/m(2)) and interval between surgery and conception (43 deliveries of patients who conceived during the first postoperative year) were compared with χ(2) tests. For parametric continuous data, t-tests or analysis of variance were used; non-parametric distributions were compared with the Wilcoxon or Kruskal-Wallis tests. RESULTS: Significantly lower mean birth weight (2993 g vs. 3253 g; p = 0.02) was observed after RYGB and the mean Z-score for birth weight was significantly closer to 0 in neonates of the LAGB group than in those of the RYGB group. However, no significant differences were noticed regarding small-for-gestational age (32.3% vs. 17.1%; p = 0.06), umbilical arterial blood pH < 7.0 (9.7% vs. 0%; p = 0.11), low Apgar scores, perinatal mortality, and NICU admission. Neonatal outcomes according to the interval from surgery to conception or to the BMI at the beginning of the pregnancy were not significantly different. CONCLUSIONS: The short-term neonatal outcomes are basically comparable in pregnancies after RYGB than after LAGB.