Search

Introduction: Despite availability of advanced therapies (ATs) for ulcerative colitis (UC), many patients fail to respond to treatment. This study examined real-world clinical and humanistic outcomes associated with current treatments in patients with UC. Methods: This cross-sectional study used US data from the Adelphi Real World Disease Specific Programme for inflammatory bowel disease from before (2017–2018) and during the COVID-19 pandemic (2020–2021). Physicians (gastroenterologists) seeing > 5 patients/month reported patients' disease characteristics, current symptoms and treatments, and reasons for treatment choices for their next seven consecutive patients aged ≥ 18 years with moderately to severely active UC before current treatment. Patients were asked to complete the EQ-5D-5L health-related quality of life (HRQoL) measure. ATs included tumor necrosis factor inhibitors (TNFis), integrin receptor antagonists, interleukin-12/23 antagonists, and Janus kinase inhibitors. Patients were classified as AT-naïve or AT-experienced based on current treatment received for ≥ 8 weeks and further classified as responders or non-responders based on symptoms, disease flare status, and remission. Descriptive analyses are presented. Results: The 2017–2018 cohort included 92 physicians and 539 patients (208 [38.6%] AT-experienced). The 2020–2021 cohort included 73 physicians and 448 patients (349 [77.9%] AT-experienced). TNFis were the most common ATs. In 2017–2018, 195 (58.9%) AT-naïve and 113 (54.3%) AT-experienced patients were non-responders; in 2020–2021 this was 57 (57.6%) and 182 (52.1%). Efficacy and induction of remission were physicians' most common reasons for AT choice. Dislike of injections/infusions was the most common reason for eligible patients not receiving biologic therapy. Numerically, non-responders (both AT-naïve and AT-experienced) had more symptoms, overall pain and fatigue, and lower HRQoL scores than responders. Conclusions: Before (2017–2018) and during the pandemic (2020–2021), over half of patients with UC did not respond to AT. Non-responders carried a high burden of disease. Alternative therapies are urgently needed to treat UC. [ABSTRACT FROM AUTHOR]

Purpose of Review: Treatment of inflammatory bowel disease (IBD) in the elderly requires special attention to treatment efficacy while considering drug safety, other medical comorbidities, and the patients' risk for treatment related adverse events. In this article, we reviewed the indications and safety of the newer IBD therapies in the older IBD patient beyond anti-TNF agents, thiopurines, and corticosteroids. Recent Findings: Vedolizumab, ustekinumab, and risankizumab have favorable side effect profiles with regards to infections and malignancy. Ozanimod has a favorable side effect profile with regards to infection and malignancy, however cardiac events and macular edema are potential risks. Tofacitinib and upadacitinib are associated with an increased risk of serious infections, herpes zoster, malignancy, and have potential for an increased risk of cardiac events and thrombosis. Summary: From a safety profile perspective, vedolizumab, ustekinumab, and risankizumab should be considered first line treatment options for moderate-to-severe IBD in the elderly. Risk-benefit discussions are indicated for ozanimod, tofacitinib, and upadacitinib. [ABSTRACT FROM AUTHOR]

Background and aims: Biologic agents have revolutionized treatment of immune mediated inflammatory diseases (IMIDs). However, despite the benefits of treatment, there is limited data on its use during pregnancy leading to significant variation in practices. We evaluated maternal, neonatal, and disease-related outcomes in pregnant women with IMIDs, comparing those with biologic exposure during pregnancy to those without exposure. Our hypothesis was that there would be no difference in outcomes between the two groups. Methods: This is a retrospective cohort study conducted at a single tertiary care center including women with Crohn's disease (CD), ulcerative colitis (UC), ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PsA) who delivered between 2010 and 2018 at The Ohio State University Wexner Medical Center. Conditions were identified by ICD-9/ICD-10 code and confirmed by chart review. Demographic data, pregnancy outcomes and disease-related data were collected. Results: There were 338 pregnancies including 100 with CD, 74 with UC, 15 with AS, 61 with RA, and 90 with PS/PsA. 23% of IMID patients had biologic exposure (biologic use within 3 months of conception) and 18% continued therapy during pregnancy. Those with biologic exposure had increased risk of post-partum disease flare (OR 3.44; 95% CI 1.29, 9.15) and were less likely to breastfeed (OR 0.44; 95% CI 0.23, 0.87). In subgroup analysis of patients with IBD, those with biologic exposure also had increased risk of post-partum flare (OR 4.55; 95% CI 1.27, 16.35). Maternal and neonatal pregnancy outcomes were similar. Conclusion: Among pregnant women with IMIDs, those that continued biologics during pregnancy had increased rates of major infection, disease related hospital admission, glucocorticoid use, and disease flare within 6 months post-partum, without any significant change in maternal or neonatal outcomes. [ABSTRACT FROM AUTHOR]

In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality. [ABSTRACT FROM AUTHOR]

Purpose of review: This review addresses our current knowledge of immune-mediated colitis (IMC) and offers a practical guide to its management. Recent findings: Due to the similarity in clinical, endoscopic, and histologic findings between IMC and inflammatory bowel disease (IBD), gastroenterologists have tailored their approach to IMC management to that of IBD. Summary: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that augment the T-cell anti-tumor response of the immune system and have demonstrated their importance in the treatment of a wide range of malignancies. With the growing benefits of ICIs, there are immune-related adverse events (irAEs) that mirror many known autoimmune diseases. Diarrhea and IMC are the most common and severe irAEs noted. No standardized guidelines exist in the management of these irAEs. [ABSTRACT FROM AUTHOR]

Purpose of review: Early- and late-onset of inflammatory bowel disease (IBD) may perhaps be etiologically distinct and potentially attributed to genetics, environmental or microbial factors. We review disease factors and clinical characteristics, as well as unique management and treatment strategies to consider when caring for the “baby” or “baby boomer” with IBD.Recent findings: Around 25% of cases of initial diagnosis of IBD is made before the age of 18 years old, and another 15-20% made after the age of 60. Crohn’s disease (CD) typically presents as ileocolonic and stricturing or penetrating phenotype among early-onset, whereas among late-onset, it is mainly colonic and inflammatory. Pediatric ulcerative colitis (UC) is mostly pan-colonic versus primarily left-sided among the elderly. Treatment goal for both age groups is primarily symptom control, with growth and development also considered among pediatric patients. Due to alterations in pharmacokinetics, careful monitoring and reduced dose should be considered. A multidisciplinary care team is necessary to ensure better clinical outcomes.Summary: Onset of disease at either spectrum of age requires careful management and treatment, with both unique disease- and age-appropriate factors carefully considered. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.METHODS:A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.RESULTS:Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.CONCLUSIONS:This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients. [ABSTRACT FROM AUTHOR]