Systematic review and meta-analysis: Safety of vedolizumab during pregnancy in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Vedolizumab is a novel monoclonal antibody used in patients with inflammatory bowel disease, often affecting women of child-bearing age. We aimed to compare maternal and fetal adverse outcomes in pregnancies of women with inflammatory bowel disease exposed to vedolizumab versus those on other treatment. METHODS: We performed a systematic literature search through December 2020 looking for studies including outcomes from pregnancies of female inflammatory bowel disease patients treated with vedolizumab. Our primary outcome was a composite of adverse pregnancy-related events in pregnancies of female patients on vedolizumab compared with those of disease-matched controls on other medication regimens. Events of interest included preterm births, early loss of pregnancy, late fetal death, elective termination of pregnancy, and congenital anomalies. RESULTS: Four studies were included in our review meeting criteria for our primary analysis. Compared with those with no vedolizumab exposure, pregnancies with vedolizumab exposure had an increase in overall adverse pregnancy-related outcomes (odds ratio [OR] 2.18, 95% confidence interval [CI], 1.52-3.13). The vedolizumab group also had increased preterm births (OR 2.16, 95% CI, 1.28-3.66), and early loss of pregnancies (OR 1.79, 95% CI, 1.06-3.01) but no difference in number of live births (OR 0.60, 95%CI, 0.36-1.00), or congenital malformations (OR 1.56, 95% CI, 0.56-4.37). CONCLUSIONS: Our systematic review highlights possible concern with the general safety of vedolizumab in pregnancy, as an increase in overall total unfavorable outcomes was observed. Premature births and early loss of pregnancy were also more prevalent in pregnant female patients on vedolizumab. It is possible these findings are confounded by disease activity, and further prospective cohort studies of vedolizumab and pregnancy outcomes are warranted.

Risk of postoperative infectious complications from medical therapies in inflammatory bowel disease.

BACKGROUND: Medications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk. OBJECTIVES: To assess the impact of perioperative IBD medications on the risk of postoperative infections within 30 days of surgery. SEARCH METHODS: We searched the Cochrane IBD Group's Specialized Register (29 October 2019), MEDLINE (January 1966 to October 2019), Embase (January 1985 to October 2019), the Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception up to October 2019, and reference lists of articles. SELECTION CRITERIA: Randomized controlled trials, quasi-randomized controlled trials, non-randomized controlled trials, prospective cohort studies, retrospective cohort studies, case-control studies and cross-sectional studies comparing participants treated with an IBD medication preoperatively or within 30 days postoperatively to those who were not taking that medication (either another active medication, placebo, or no treatment). We included published study reports and abstracts. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and extracted data. The primary outcome was postoperative infection within 30 days of surgery. Secondary outcomes included incisional infections and wound dehiscence, intra-abdominal infectious complications and extra-abdominal infections. Three review authors assessed risks of bias using the Newcastle-Ottawa Scale. We contacted authors for additional information when data were missing. For the primary and secondary outcomes, we calculated odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) using the generic inverse variance method. When applicable, we analyzed adjusted and unadjusted data separately. We evaluated the certainty of the evidence using GRADE. MAIN RESULTS: We included 68 observational cohort studies (total number of participants unknown because some studies did not report the number of participants). Of these, 48 studies reported including participants with Crohn's disease, 36 reported including participants with ulcerative colitis and five reported including participants with indeterminate colitis. All 42 studies that reported urgency of surgery included elective surgeries, with 31 (74%) of those also including emergency surgeries. Twenty-four studies had low risk of bias while the rest had very high risk. Based on pooling of adjusted data, we calculated ORs for postoperative total infection rates in participants who received corticosteroids (OR 1.70, 95% CI 1.38 to 2.09; low-certainty evidence), immunomodulators (OR 1.29, 95% CI 0.95 to 1.76; low-certainty evidence), anti-TNF agents (OR 1.60, 95% CI 1.20 to 2.13; very low-certainty evidence) and anti-integrin agents (OR 1.04, 95% CI 0.79 to 1.36; low-certainty evidence). We pooled unadjusted data to assess postoperative total infection rates for the use of aminosalicylates (5-ASA) (OR 0.76, 95% CI 0.51 to 1.14; very low-certainty evidence). One secondary outcome examined was wound-related complications in participants using: corticosteroids (OR 1.41, 95% CI 0.72 to 2.74; very low-certainty evidence), immunomodulators (OR 1.35, 95% CI 0.96 to 1.89; very low-certainty evidence), anti-TNF agents (OR 1.18, 95% CI 0.83 to 1.68; very low-certainty evidence) and anti-integrin agents (OR 1.64, 95% CI 0.77 to 3.50; very low-certainty evidence) compared to controls. Another secondary outcome examined the odds of postoperative intra-abdominal infections in participants using: corticosteroids (OR 1.53, 95% CI 1.28 to 1.84; very low-certainty evidence), 5-ASA (OR 0.77, 95% CI 0.45 to 1.33; very low-certainty evidence), immunomodulators (OR 0.86, 95% CI 0.66 to 1.12; very low-certainty evidence), anti-TNF agents (OR 1.38, 95% CI 1.04 to 1.82; very low-certainty evidence) and anti-integrin agents (OR 0.40, 95% CI 0.14 to 1.20; very low-certainty evidence) compared to controls. Lastly we checked the odds for extra-abdominal infections in participants using: corticosteroids (OR 1.23, 95% CI 0.97 to 1.55; very low-certainty evidence), immunomodulators (OR 1.17, 95% CI 0.80 to 1.71; very low-certainty evidence), anti-TNF agents (OR 1.34, 95% CI 0.96 to 1.87; very low-certainty evidence) and anti-integrin agents (OR 1.15, 95% CI 0.43 to 3.08; very low-certainty evidence) compared to controls. AUTHORS' CONCLUSIONS: The evidence for corticosteroids, 5-ASA, immunomodulators, anti-TNF medications and anti-integrin medications was of low or very low certainty. The impact of these medications on postoperative infectious complications is uncertain and we can draw no firm conclusions about their safety in the perioperative period. Decisions on preoperative IBD medications should be tailored to each person's unique circumstances. Future studies should focus on controlling for potential confounding factors to generate higher-quality evidence.

Noninvasive Ventilation in Patients With Hematologic Malignancy.

INTRODUCTION: Noninvasive ventilation (NIV) is commonly used as first-line therapy for immunocompromised patients with acute respiratory failure. However, it may not be appropriate for all patients, as failure of NIV and delayed endotracheal intubation (ETI) may increase mortality. We report our center's experience and outcomes for patients with active hematologic malignancy (HM) treated with NIV. METHODS: We conducted a retrospective study of consecutive patients with HM who were admitted to the intensive care unit (ICU) of Mount Sinai Hospital for acute respiratory failure between January 1, 2010, and May 31, 2015, and were initially treated with NIV. We compared the characteristics of patients who were successfully treated with NIV and avoided intubation and those who failed NIV. RESULTS: Seventy-nine patients (mean age 56 ± 14 years, mean Acute Physiology and Chronic Health Evaluation II score 27 ± 5) with HM were treated with NIV for acute respiratory failure. The etiology of respiratory failure was multifactorial in 31 (39%) patients, with features of pneumonia in 61 (77%) patients, severe sepsis or septic shock in 33 (42%) patients, and pulmonary edema in 24 (30%) patients. The majority of patients were admitted with acute leukemia (n = 60, 76%), 8 (10%) with lymphoma, and 11 (14%) with chronic leukemia, multiple myeloma, or myelodysplastic syndrome. Of the 79 patients treated with NIV, 44 (56%) failed NIV and required ETI, 7 (9%) had a do-not-intubate (DNI) order and died, and 28 (35%) avoided ETI. Compared with patients who avoided ETI, those who failed NIV or had a DNI order and died were more likely to have acute leukemia (84% vs 61%; P = .02) and at baseline had higher Paco2 (39 vs 30; P = .038), higher fraction of inspired oxygen (Fio2) requirements (0.6 vs 0.4; P = .002), and more vasopressor use (31% vs 11%; P = .059). The ICU mortality was 42%; 3-month mortality was 57% overall and was significantly lower in the NIV success patients compared with the NIV failure group (21% vs 74%; P < .001). CONCLUSION: Two-thirds of patients with HM and respiratory failure failed NIV and required ETI, and had high subsequent mortality. Patients who failed NIV had higher Paco2, higher Fio2, and a trend toward more vasopressor use.