The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update was to rapidly review the emerging evidence and provide timely expert recommendations regarding ...the management of patients with inflammatory bowel disease during the coronavirus disease 2019 pandemic. This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely perspective on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology.
Pregnant women with inflammatory bowel disease (IBD) may require biologic or thiopurine therapy to control disease activity. Lack of safety data has led to therapy discontinuation during pregnancy, ...with health repercussions to mother and child.
Between 2007 and 2019, pregnant women with IBD were enrolled in a prospective, observational, multicenter study across the United States. The primary analysis was a comparison of 5 outcomes (congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infant infections) among pregnancies exposed vs unexposed in utero to biologics, thiopurines, or a combination. Bivariate analyses followed by logistic regression models adjusted for relevant confounders were used to determine the independent effects of specific drug classes on outcomes of interest.
Among 1490 completed pregnancies, there were 1431 live births. One-year infant outcomes were available in 1010. Exposure was to thiopurines (n = 242), biologics (n = 642), or both (n = 227) vs unexposed (n = 379). Drug exposure did not increase the rate of congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infections during the first year of life. Higher disease activity was associated with risk of spontaneous abortion (hazard ratio, 3.41; 95% confidence interval, 1.51–7.69) and preterm birth with increased infant infection (odds ratio, 1.73; 95% confidence interval, 1.19–2.51).
Biologic, thiopurine, or combination therapy exposure during pregnancy was not associated with increased adverse maternal or fetal outcomes at birth or in the first year of life. Therapy with these agents can be continued throughout pregnancy in women with IBD to maintain disease control and reduce pregnancy-related adverse events. ClinicalTrials.gov, Number: NCT00904878.
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Abstract
Background and Aims
Vedolizumab is a gut-selective antibody to α 4 β 7 integrin, approved to treat moderate-to-severe ulcerative colitis and Crohn’s disease in adults. Clinical trial data ...on patients meeting protocol-specified criteria may not reflect real-world clinical practice. This is a descriptive analysis of 4 years of post-marketing safety data on vedolizumab.
Methods
The Vedolizumab Global Safety Database contains all adverse event reports collated by Takeda Pharmaceutical Company Ltd since vedolizumab approval May 20, 2014. Adverse event reports received between approval and May 19, 2018 were identified using Medical Dictionary for Regulatory Activities version 21.0 Preferred Terms. Adverse event frequencies were calculated and categorised.
Results
In approximately 208 050 patient-years of vedolizumab exposure, 32 752 patients reported 80 218 events. In patients with Crohn’s disease or ulcerative colitis, 37 662 and 34 259 events occurred in 14 191 and 14 042 patients, respectively, and 8297 events occurred in 4519 individuals with other off-label or unreported indications. Overall, 5230 14%; Crohn’s disease and 3580 10%; ulcerative colitis events were serious. Most frequently reported were gastrointestinal events (Crohn’s disease, 6156 16%; ulcerative colitis, 5701 17%). Patients with Crohn’s disease or ulcerative colitis reported 251 malignancies <1%, 402 hepatobiliary events <1%, and 5876 infections (1137 serious 19%, 301 opportunistic 5%). Patients aged ≥70 years 2326 patients reported <10% of events.
Conclusions
Adverse event patterns were consistent with clinical trials, with no new safety concerns. Most reported events were non-serious and event frequency was low, considering patient-years of exposure. Although limitations of post-marketing safety reports require acknowledgement, these real-world data support a favourable safety profile of vedolizumab.
Digging into the Histology Paknikar, Raghavendra; Alpert, Lindsay; Cohen, Russell D. ...
The New England journal of medicine,
10/2023, Letnik:
389, Številka:
14
Journal Article
Recenzirano
A 33-year-old man with ulcerative colitis presented with bloody diarrhea, an 8-month history of worsening fatigue and diarrhea, and a 4-month history of fevers, drenching night sweats, and ...unintentional weight loss.
We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined.
Utilizing data ...from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA).
As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither.
In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.
Abstract
Background
The purpose of this study was to compare the long-term safety of infliximab and nonbiologic agents as Crohn's disease (CD) therapy.
Methods
Patients with CD were prospectively ...evaluated in this large, observational registry.
Results
Patients (n = 6273) participated in this observational registry from July 1999 through March 2012; 3440 (54.8%) received infliximab (20,971 patient-years), and 2833 (45.2%) received other treatments only (14,806 patient-years). Overall, 59,875 infliximab infusions were administered (80%, 5 mg/kg); 3006 (89.9%) patients received ≥2 infusions. Adverse events (AEs), most commonly those related to CD (eg, abdominal pain, diarrhea), and serious AEs occurred at a higher rate among infliximab-treated patients. Mortality (0.57/100 patient-years, 0.67/100 patient-years) and malignancy rates (0.69/100 patient-years, 0.71/100 patient-years) for infliximab-treated and other-treatments-only patients, respectively, were generally similar. Serious infection rates were higher for infliximab-treated (2.15/100 patient-years) than other-treatments-only patients (0.86/100 patient-years). Infliximab dose was not associated with mortality or serious infection. An increased risk of serious infection was observed with age (>52 years vs ≤30 years) when examined in infliximab-treated patients. Nonserious cerebrovascular accidents (13 events, 0.06/100 patient-years; 5 events, 0.03/100 patient-years) and pulmonary embolisms (11 events, 0.05/100 patient-years; 4 events 0.03/100 patient-years) also occurred at higher rates among infliximab-treated patients than other-treatments-only patients.
Conclusions
Through more than 13 years of registry experience and an overall median duration of patient follow-up >6 years, mortality was similar between the infliximab-treated and other-treatments-only groups. These final cumulative results are representative of real-world experience among infliximab-treated patients with CD and are consistent with the known risks of disease activity and tumor necrosis factor antagonist therapy.
In women with inflammatory bowel diseases (IBDs), exposure to immunomodulator or biologic therapy has not been associated with adverse events during pregnancy or outcomes of newborns. We investigated ...whether exposure of patients to these agents during pregnancy affects serologic responses to vaccines in newborns.
We collected data from the Pregnancy in IBD and Neonatal Outcomes registry, which records outcomes of pregnant women with diagnosis of IBD receiving care at multiple centers in the United States, from 2007 through 2016. Serum samples collected from infants at least 7 months old were analyzed for titers of antibodies to Haemophilus influenzae B (HiB) or tetanus toxin; mothers completed a survey of vaccine practices and outcomes from July 2013 through October 2016. Umbilical cord blood samples from 33 infants were assayed for concentration of biologic agents. Vaccination response was compared between infants born to mothers exposed to biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, natalizumab, vedolizumab, or ustekinumab-either as a single agent or in combination with an immunomodulator, at any time between conception and delivery) and infants born to unexposed mothers.
A total of 179 women completed the vaccine survey (26 biologic unexposed, 153 exposed to a biologic agent). We found no significant difference in proportions of infants with protective antibody titers against HiB born to exposed mothers (n = 42, 71%) vs unexposed mothers (n = 8, 50%) (P = .41). We also found no difference in the proportion of infants with protective antibody titers to tetanus toxoid born to exposed mothers (80%) vs unexposed mothers (75%) (P = .66). The median concentration of infliximab in cord blood did not differ significantly between infants with vs without protective antibody titers to HiB (P = .30) or tetanus toxoid (P = .93). Mild reactions were observed in 7/40 infants who received rotavirus vaccine and whose mothers had been exposed to biologic therapies.
Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy.
Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum. Long-term therapy is generally required to achieve and maintain disease control.
In May 2021 the US Food ...and Drug Administration approved the use of ozanimod in patients with moderate to severe UC. We describe the first report of the use of ozanimod in real-world clinical practice.
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