Decreasing Risk of Relapse after Anti-TNF Withdrawal in Inflammatory Bowel Disease
De-escalation of anti-tumor necrosis factor (TNF) treatment in patients with inflammatory bowel disease (IBD) in remission is a strategy to reduce the side effects of the treatment, including the risks of serious infections and malignancies, while decreasing health care expenditures and treatment burdens. But this strategy is associated with a high relapse rate. A prospective observational study from the Netherlands offers data that can guide clinicians and inform patient selection for such treatment de-escalation. The study concludes that strict patient selection based on endoscopic healing as well as the maintenance of mesalamine treatment in ulcerative colitis may lower the risk of relapse.
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The multicenter, prospective study in adult patients with Crohn disease (CD), ulcerative colitis, or IBD – unclassified (IBDU) enrolled 81 patients, 51% with CD, with a median follow-up of 2 years. Those included in the study had achieved at least 6 months of corticosteroid-free clinical remission and endoscopic healing and had elected to discontinue anti-TNF therapy between 2018 and 2020. Researchers evaluated the following as potential predictors of relapse:
- complete endoscopic healing: endoscopic Mayo score of 0 or Simple Endoscopic Score for CD (SES-CD) of 0 to 2
- partial endoscopic healing: endoscopic Mayo score of 1 or SES-CD of 3 to 4
- anti-TNF agent trough levels
- use of immunomodulators or mesalamine.
The patients could continue or start mesalamine or immunomodulator (thiopurine or methotrexate) treatment at the discretion of the treating physician. Follow-up started at the time of the last dose of the anti-TNF agent, and patients were monitored by measuring C-reactive protein (CRP) and fecal calprotectin at 3, 6, 12, and 24 months and by endoscopy at 12 weeks. In addition, if relapse occurred, monitoring included CRP, fecal calprotectin, and anti-TNF trough levels at 3 months. In addition, the following questionnaires were sent to participants at 0, 3, 6, 12, and 24 months of follow-up, at time of relapse, and 3 months after relapse:
- Harvey-Bradshaw Index (HBI) for CD patients
- Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis and IBDU patients
- Short IBD Quality of Life Questionnaire (SIBDQ) for all patients.
Clinical remission was defined as SCCAI/HBI scores <5; biochemical remission was defined as CRP <10 mg/L and fecal calprotectin <250 mcg/g; endoscopic healing was defined as Mayo score <2 or SES-CD <5 without large ulcers; and clinical relapse was defined as SCCAI/HBI score ≥5 with ≥3-point increase from baseline.
All patients in the study met the criteria for endoscopic healing, and 71 had complete endoscopic healing. The risk of relapse after withdrawal of anti-TNF treatment among patients with any endoscopic healing remained high, but complete endoscopic healing was associated with a considerably lower risk of relapse. At 12 months, 7 patients (70%) with partial endoscopic healing had relapsed, compared with 25 patients (35%) with complete endoscopic healing. The large difference in this relapse risk underscores the clinical importance of this finding.
The use of mesalamine was independently associated with a decreased risk of relapse in patients with ulcerative colitis/IBDU (adjusted hazard ratio, 0.08) but not CD. However, continuing treatment with immunomodulators does not offer such protection. It’s possible that selection bias may have played a part in this result, since the decision to continue or start these agents was up to the treating physician. No other potential predictors for relapse were identified on analysis.
After relapse, 30 patients restarted anti-TNF therapy (26 with the same agent), and clinical remission was regained in 73% at 3 months and 90% at 12 months. The remission rate at 3 months did not differ between patients restarting single-agent anti-TNF therapy or those restarting with combination therapy (77% vs. 67%). Reported quality of life and general well-being improved to baseline once remission was restored. This underscores the feasibility of a strategy of combining withdrawal with reintroduction upon relapse. (Mahmoud, R., et al. (2023). Complete endoscopic healing is associated with lower relapse risk after anti-TNF withdrawal in inflammatory bowel disease. Clin Gastroenterol Hepatol, 21(3), 750–760.E4. Retrieved March 2023 from https://www.cghjournal.org/article/S1542-3565(22)00820-5/fulltext)
Released: March 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
Azithromycin Given during Labor Reduces Risk of Maternal Postpartum Sepsis
A single dose of azithromycin given during labor reduces the risk of maternal sepsis and death after childbirth. The World Health Organization has prioritized reduction of maternal sepsis in its efforts to decrease maternal deaths worldwide. Sepsis is a life-threatening condition that occurs as the immune system overreacts to infection, leading to tissue and organ damage. It accounts for 10% of maternal deaths and is among the top three causes of maternal deaths worldwide.
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Azithromycin is effective against a wide range of bacteria and has been shown to reduce maternal infection when given IV during cesarean delivery, reducing risk by 50%. A large multinational trial that enrolled more than 29,000 women in 7 member countries of the Global Network for Women and Children’s Health Research, A-PLUS (Azithromycin Prevention in Labor Use Study) was conducted between September 2020 and August 2022. The trial enrolled women in labor at 28 weeks’ gestation or more; who had no known infections, cardiac issues, or known allergies to antibiotics; and who were not in an advanced stage of labor (that is, dilation >6 cm). Enrolled patients were randomized to receive a 2-g oral dose of azithromycin (N = 14,590 women, 14,687 neonates) or placebo (N = 14,688 women, 14,782 neonates). The outcomes were a composite of maternal sepsis or death and a composite stillbirth or neonatal death or sepsis. Patients were educated about what signs or symptoms of infection to watch for and when to report those or to return for further health care; the researchers implemented guidelines to monitor patient’s temperature.
Only 1.6% (n = 277) of women who received azithromycin developed sepsis or died within 6 weeks after delivery, compared to 2.4% (n = 344) who received a placebo dose (relative risk, 0.67). The differences in the maternal primary outcome appear to mostly be due to the decreased incidence of sepsis (1.5% azithromycin [n = 219] vs. 2.3% placebo [n = 339]), with a relative risk of 0.65. Death from sepsis occurred in less than 0.1% of each group. Those who received the dose of azithromycin were also less likely to develop endometriosis and other infections and had fewer hospital readmissions and unscheduled health care visits compared with placebo. Endometriosis occurred in 1.3% of patients in the azithromycin group and in 2.0% of those in the placebo group (relative risk, 0.66). Wound infection, whether of cesarean incision or perineal injury, occurred in 1.6% of those in the azithromycin group and in 2.2% of those in the placebo group (relative risk, 0.71).
The incidence of stillbirth or neonatal death or sepsis was similar in the two groups: 10.5% in the azithromycin arm (n = 1,540) vs. 10.3% in the placebo arm (n = 1,526); relative risk, 1.02. Neonatal sepsis occurred in 9.8% (n = 1,433) and 9.6% (n = 1,407) of infants in the azithromycin and placebo arms, respectively. Incidence of stillbirth (0.4%) and neonatal deaths (1.5%) did not differ in the two groups.
These findings can lead to a simple intervention that will be lifesaving, especially in low- and middle-income countries. (Alpha Galileo. SciDev.Net. (2023). Preventative antibiotic during labour “saves lives.” Retrieved March 2023 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230703?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230703; Tita, A. T. N., et al. (2023). Azithromycin to prevent sepsis or death in women planning a vaginal birth. New Engl J Med, 388, 1161–1170. Retrieved March 2023 from https://www.nejm.org/doi/full/10.1056/NEJMoa2212111)
Released: March 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
Remdesivir for Severe COVID-19: Who Benefits?
The broad-spectrum antiviral medication remdesivir was one of the first medications approved for treatment of COVID-19, as early as 2020. A new review of eight clinical trials, including meta-analysis of individual patient data, allows identification of the subgroup that can most benefit from remdesivir treatment. The meta-analysis showed reduced mortality in patients hospitalized with COVID-19 who required no respiratory support or only conventional low-flow oxygen.
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A research team from the University of Basel analyzed results from eight randomized, controlled trials (RCTs) that assessed the benefits and harms of remdesivir compared with placebo or usual care in these patients. The analysis included data from more than 10,000 unvaccinated patients from more than 40 countries who were treated for COVID-19 in hospital between February 2020 and April 2021, more than 99% of the patients involved in RCTs on this topic worldwide. Results of the meta-analysis were published in The Lancet Respiratory Medicine.
Remdesivir lowered mortality over a 4-week observation period by roughly 2%, leading to 20 fewer deaths per 1,000 patients. Within 28 days of randomization, 662 (12.5%) of 5,317 patients assigned to remdesivir and 706 (14.1%) of 5,005 patients not assigned to remdesivir died (adjusted odds ratio [OR], 0.88). Meta-analysis showed that patients who didn’t receive oxygen treatment or only received conventional oxygen support experienced a significant survival benefit from remdesivir. Out of those who received no oxygen support or low-flow oxygen, 409 (9.1%) of 4,773 patients assigned to remdesivir compared with 465 (11.2%) of 4,159 patients not assigned to remdesivir died (adjusted OR, 0.8); however, no significant difference was seen for those who received more respiratory support: among those who received high-flow oxygen or ventilation, 253 (30%) of 844 patients assigned to remdesivir died compared to 241 (28.5%) of 846 patients not receiving remdesivir (adjusted OR, 1.01). No credible subgroup effect was found for other variables, such as time after symptom onset that remdesivir treatment began, patient age, presence of comorbidities, the enrollment period, or corticosteroid use.
The number of patients either requiring new mechanical ventilation or dying up to day 28 was also lower in the remdesivir group: 988 of 5,346 patients (18.5%) vs. the non-remdesivir group: 1,123 of 5,034 patients (22.3%) (adjusted OR, 0.81). Remdesivir use was not associated with earlier discharge from the hospital; the absolute difference in median time to hospital discharge was 0.16 days.
These results align with World Health Organization guidelines, which recommend remdesivir for patients with severe but noncritical COVID-19 infection. Further study is needed to determine the absolute risk reduction in a better-protected population. Further research can determine the effect size in patients who have received a complete series of COVID-19 vaccine or booster doses and in those with immunity from prior COVID-19 infection. (Alpha Galileo. University of Basel. (2023). When is remdesivir effective for COVID-19? Retrieved March 2023 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230551?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230551; Amstutz, A., et al. (2023). Effects of remdesivir in patients hospitalised with COVID-19: A systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir Med. Advance online publication. Retrieved March 2023 from https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(22)00528-8.pdf)
Released: March 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer