Therapeutic Advances in Gastroenterology最新文献

Patients with inflammatory bowel disease (IBD) are not at increased risk of SARS-CoV-2 infection compared to the general population, and most are not at increased risk for severe disease. COVID-19 is nonetheless common, and vaccination is critical. Four safe and efficacious vaccines are now available for the prevention of COVID-19, with most data available for mRNA vaccines. Patients with IBD have a robust humoral response to vaccination with rates of seroconversion exceeding 95% following a two-dose mRNA vaccine series and 99% following a three-dose mRNA series, although those on certain therapies including anti-tumor necrosis factor α agents may have lower antibody concentrations and waning of antibodies over time. Additionally, rates of cell-mediated immune response, even in those patients with IBD who did not have evidence of humoral immunity, are high. Vaccines are safe and have not been associated with flares in disease activity. Gastroenterology providers should take an active role in ensuring patients with IBD are appropriately vaccinated against COVID-19.

Over the past two decades, 11 biologic agents have been approved for use in most countries for the treatment of moderate-to-severe inflammatory bowel disease (IBD). Antitumor necrosis factor α (anti-TNF) agents are commonly used as the first biologic in clinical practice, and nearly all pivotal studies of induction therapy enrolled patients with and without prior use of anti-TNF therapy. This narrative review presents a reasonable approach to devising treatment sequences, examining the magnitude of benefit for each drug versus placebo or active comparator and then considering how that benefit changes with prior anti-TNF treatment. Data from ULTRA 2, GEMINI 1, VARSITY, and True North in patients with ulcerative colitis indicate that induction adalimumab, vedolizumab, and ozanimod showed lower clinical remission rates after anti-TNF therapy, while UNIFI, OCTAVE 1&2, and U-ACHIEVE/U-ACCOMPLISH show ustekinumab, tofacitinib, and upadacitinib did not. In patients with Crohn's disease, endoscopic remission or mucosal healing after induction therapy rather than clinical remission as well as assessment of persistent endoscopic remission are good measures of long-term disease outcomes. Considering the drugs for which data on endoscopic remission rates are available, EXTEND and GEMINI 2&3 show adalimumab and vedolizumab with persistently lower endoscopic remission rates after prior anti-TNF therapy, while IM-UNIFI, SEAVUE, and FORTIFY show ustekinumab and risankizumab did not. Data from the multicenter retrospective EVOLVE study indicate that the effectiveness of anti-TNF therapy does not seem to be significantly impacted by prior vedolizumab therapy, and may further suggest the benefit of using vedolizumab as a first-line biologic. As adverse event rates remain low across all treatments, the magnitude of harm from untreated or poorly treated disease far outweighs harm from any individual therapy. Regardless of the treatment sequence, careful monitoring for early signs of treatment nonresponse and switching to another potentially highly active therapy are critical to effective management of IBD.

Background: Flixabi^TM (SB2) is a biosimilar of the reference infliximab (IFX), Remicade^®. Published evidence on long-term, real-world use of SB2 in patients either IFX naive or transitioned from prior IFX is scarce.

Objectives: We evaluated persistence, effectiveness, and safety of SB2 over 12 months in adults with IBD [Crohn's disease (CD) and ulcerative colitis (UC)], participating in PERFUSE.

Design: PERFUSE is a long-term, non-interventional, multicenter study of patients receiving SB2 at specialist sites across France.

Methods: SB2 treatment was initiated in September 2017, either as first IFX treatment (IFX naive), after transition from treatment with reference IFX (IFX ref) or another IFX biosimilar (IFX bs), or both IFX ref and IFX bs (IFX multiswitch). Outcomes up to Month 12 (±2) include persistence on SB2 (primary outcome measure), SB2 dose, disease status, immunogenicity, and safety.

Results: This final 12-month analysis of patients with IBD includes 569 with CD and 168 with UC. Persistence [95% confidence interval (CI)] at Month 12 was CD: 89% (77.2; 94.9), UC: 78.5% (58.2; 89.8) for IFX naive; CD: 94% (91.0; 96.1), UC: 92.8% (84.8; 96.7) for IFX ref; CD: 91.6% (86.0; 95.0), UC: 94.2% (83.1; 98.1) for IFX bs; and CD 100% (100; 100), UC 100% (100; 100) for IFX multiswitch. In the CD and UC cohorts, disease activity among IFX naive patients declined from baseline to Month 12; with any prior IFX, the proportions of patients in remission at baseline, Month 6, and Month 12 remained unchanged in the UC cohort, and were comparable or higher in the CD cohort. No immunogenicity or safety signals were detected.

Conclusions: Patients with IBD can be initiated on SB2 or transitioned from IFX ref and/or IFX bs to SB2, with no loss of disease control or safety concerns, with >75% of naive and >90% of transitioned patients continuing on SB2 treatment at 12 months.

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal condition which entails a high burden in the quality of life (QoL) of patients. Nutritional interventions have been proposed to alleviate symptoms, since still no effective treatments exist for IBS.

Objectives: Our aim is to analyse the feasibility of the use of starch- and sucrose-reduced diet (SSRD).

Design: In this study, we used a SSRD accompanied by nutritional and culinary recommendations to measure the effects in IBS patients with diarrhoea.

Methods: In all, 34 participants completed a 4-week nutritional intervention based on SSRD. Symptoms, QoL and dietary habits were assessed by several questionnaires that were completed at the beginning, daily, after 2 weeks, at the end, and after 2 months.

Results: 85.29% of the participants reached the primary endpoint [reduction of 50 points or more in IBS-symptom severity scale (SSS)], and 58.82% the secondary endpoint (reduction of 50% or more in IBS-SSS). The relief of symptoms and improvement of the QoL were significant after 2 weeks of intervention, at the end and after 2 months. Dietary habits were consistent with the diet and high adherence was achieved.

Conclusions: SSRD and individualized nutritional and culinary guidance improved symptoms and QoL of IBS patients with diarrhoea, with a high adherence.

An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.

Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited.

Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.

Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.

Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively.

Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants).

Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease.

Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland.

Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019.

Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment.

Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years.

Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high.

Registration: ENCePP (EUPAS34119).

Background: Pregabalin is worldwidely licensed for the treatment of a variety of pain syndromes and supposed to be a potential candidate for the centrally mediated abdominal pain syndrome (CAPS).

Objectives: To investigate the efficacy of pregabalin on nociceptive and emotional symptoms in CAPS patients.

Design: This is an open-label randomized controlled trial.

Methods: CAPS patients were randomized to receive pregabalin 75 mg (P group), pinaverium bromide 50 mg (PB group), or pregabalin combined pinaverium bromide regimen (P + PB group) three times daily for 4 weeks. Questionnaires were completed biweekly. The primary outcomes were defined as the average abdominal pain scores of severity and frequency at weeks 2 and 4. Secondary outcomes included the reduction in abdominal pain scores, Somatic Self-rating Scale (SSS), Patient Health Questionnaire-15 (PHQ-15), and Generalized Anxiety Disorder Scale 7 (GAD-7) scales obtained at the end of trial to the baseline.

Results: Totally, 102 eligible patients were recruited and randomized. The mean severity scores of abdominal pain were 1.39 ± 1.28, 0.97 ± 1.43 versus 2.91 ± 1.44 (p < 0.0001) in P or PB + P group versus PB group at week 2 and were 0.90 ± 1.21, 1.28 ± 1.87 versus 2.74 ± 1.75 (p < 0.0001) at week 4. The mean frequency scores were 2.55 ± 2.55, 2.03 ± 2.80 versus 5.12 ± 2.09(p < 0.0001) in P or PB + P group versus PB group at week 2 and were 1.72 ± 2.46, 2.00 ± 2.90 versus 4.55 ± 2.55 (p < 0.0001) at week 4. When comparing the changes in SSS, PHQ-15, and GAD-7 scores, patients accepting pregabalin or pregabalin combination regimen reported a more decrease than pinaverium bromide recipients (p = 0.0002, p = 0.0002, and p = 0.0033).

Conclusion: This trial suggests that pregabalin may be beneficial for CAPS abdominal pain and concomitant somatic or anxiety symptoms.

Registration: www.chictr.org.cn (ChiCTR1900028026).