SARS-CoV-2
Ursodeoxycholic acid reduces COVID-19 severity
Exposing patients with cirrhosis to ursodeoxycholic acid (UDCA), a naturally occurring bile acid, may decrease the likelihood of SARS-CoV-2 infection and reduce at least moderate and severe/critical COVID-19.
The authors conducted a retrospective cohort study among 1,607 participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort. They compared participants with exposure to UDCA, with a propensity score matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. Outcomes included SARS-CoV-2 infection; varying severities of COVID-19; and COVID-19-related death.
UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection. Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19, at least moderate COVID-19, and severe or critical COVID-19.
Reference: John BV, Bastaich D, Webb G, et al Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis. J Intern Med. 2023;293(5):636-647.
POLYMYALGIA RHEUMATICA
New biologic approved
The FDA has approved sarilumab for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.1,2
Sarilumab is an interleukin-6 receptor antagonist.
Sarilumab comes with a boxed warning for serious infections leading to hospitalization or death, including bacterial, viral, invasive fungal, and other opportunistic infections, and cases of tuberculosis.2
It is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.
Other warnings issued with the use of sarilumab include neutropenia, thrombocytopenia, elevated liver enzymes, lipid abnormalities, and gastrointestinal perforations. Sarilumab should be avoided with the use of live vaccines due to the risk of infection.2
The most common adverse reactions include neutropenia, increased serum alanine transaminase levels, injection site erythema, upper respiratory infections, and urinary tract infections.2
References: 1. Kevzara(R) (sarilumab) approved by FDA as first and only biologic indicated for patients with polymyalgia rheumatica. Sanofi. 2023. http://www.news.sanofi.us/2023-03-01-Kevzara-R-sarilumab-approved-by-FDA-as-firs. Accessed April 5, 2023.
2. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
PROCTOCOLECTOMY
Vedolizumab a potentially more effective treatment
Treatment with vedolizumab, an integrin receptor antagonist, may effectively induce remission in patients with chronic pouchitis after undergoing restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA), according to a study published in the New England Journal of Medicine.
In a phase 4, double-blind, randomized trial, 102 adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis were assigned to receive I.V. vedolizumab at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. Each patient received concomitant ciprofloxacin from weeks 1 to 4.
The primary endpoint for the study was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of 4 or less and a reduction from baseline of 2 or more points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Secondary endpoints included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of 2 or more points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of 6 or less and a reduction from baseline of 3 or more points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.
The incidence of mPDAI-defined remission at week 14 was 31% with vedolizumab and 10% with placebo. Other differences favoring vedolizumab included mPDAI-defined remission at week 34; mPDAI-defined response at weeks 14 and 34; and PDAI-defined remission at weeks 14 and 34.
Serious adverse events were reported in 6% of the vedolizumab group and 8% of the placebo group.
Reference: Travis S, Silverberg MS, Danese S, et al Vedolizumab for the treatment of chronic pouchitis. N Engl J Med. 2023;388(13):1191-1200. doi:10.1056/nejmoa2208450.
PEDIATRIC TBI
Ketamine may have utility in severe TBI
Ketamine may be a plausible treatment for children with severe traumatic brain injury (TBI), according to a study published in Critical Care Medicine, a Wolters Kluwer Lippincott Williams & Wilkins journal.
In a retrospective observational study, authors analyzed data from 33 patients, ages 1 month to 16 years, 22 of whom received bolus doses of ketamine, with 127 doses analyzed. Demographics, patient, and injury characteristics were similar between patients who did versus did not receive ketamine boluses.
The authors found no significant difference in intracranial pressure (ICP) or cerebral perfusion pressure (CPP) from the baseline measurement. Eighteen ketamine doses were given during ICP crises in 11 patients. ICP decreased following these doses; threshold-subtracted CPP rose.
Reference: Laws JC, Vance EH, Betters KA, et al Acute effects of ketamine on intracranial pressure in children with severe traumatic brain injury. Crit Care Med. 2023;51(5):563-572. doi:10.1097/ccm.0000000000005806.
CANDIDEMIA AND CANDIDIASIS
New treatment
Cidara Therapeutics and Melinta Therapeutics announced that the FDA has approved rezafungin injection, an echinocandin antifungal, for the treatment of candidemia and invasive candidiasis.1
The approval is based on data published in the New England Journal of Medicine that indicate rezafungin is noninferior to caspofungin, a current once-daily standard of care, for primary endpoints of day-14 global cure (consisting of clinical cure, radiological cure, and mycological eradication) and 30-day all-cause mortality.2
About 200 patients were randomly assigned to receive rezafungin or caspofungin.
At the day-14 global cure endpoint, 59% of the rezafungin group and 61% of the caspofungin group had achieved this status.
About 24% of the razafungin group and 21% of the caspofungin group had died or an unknown survival status by day 30.
The percentages of those who experienced at least one adverse event were 91% in the rezafungin group and 85% in the caspofungin group. The most common adverse events were pyrexia, hypokalemia, pneumonia, septic shock, and anemia. About 56% of the rezafungin group and 53% of the caspofungin group experienced serious adverse events.
References: 1. Wpengine. Cidara Therapeutics and Melinta Therapeutics announce FDA approval of Rezzayo(TM) (Rezafungin for Injection) for the treatment of Candidemia and invasive candidiasis. Cidara Therapeutics. 2023. http://www.cidara.com/news/cidara-therapeutics-and-melinta-therapeutics-announce. Accessed April 5, 2023.
2. Thompson GR, Soriano A, Cornely OA, et al Rezafungin versus Caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. 2023;401(10370):49-59. doi:10.1016/s0140-6736(22)02324-8.
ACUTE LIVER FAILURE
FDA limit on acetaminophen reduced hospitalizations
A limit on acetaminophen dosage resulted in a decrease in hospitalizations and the proportion per year of acute liver failure (ALF) cases involving acetaminophen and opioid toxicity, finds a study published in JAMA.
In January 2011, the FDA limited acetaminophen dosage to 325 mg/tablet in combination acetaminophen and opioid medications, with manufacturer compliance required by 2014.
Researchers of the present study reviewed hospitalization data from 2007 to 2019 involving ICD-9 and ICD-10 codes consistent with both acetaminophen and opioid toxicity from the National Inpatient Sample, a large US hospitalization database, and ALF cases from 1998 to 2019 involving acetaminophen and opioid products from the Acute Liver Failure Study Group.
From Q1 2007 through Q4 2019, there were 39,606 hospitalizations involving acetaminophen and opioid toxicity; 66.8% of these cases were among women. From Q1 1998 through Q3 2019, there were 2,631 ALF cases, of which 465 involved acetaminophen and opioid toxicity; 85.4% of these cases were among women.
The authors write that the odds of hospitalizations with acetaminophen and opioid toxicity increased 11% per year before the FDA's announcement and decreased 11% per year after the announcement. The percentage of ALF cases involving acetaminophen and opioid toxicity increased 7% per year before the announcement and decreased 16% per year after the announcement.
Reference: 1. Orandi BJ, McLeod MC, MacLennan PA, et al Association of FDA mandate limiting acetaminophen (paracetamol) in prescription combination opioid products and subsequent hospitalizations and acute liver failure. JAMA. 2023;329(9):735-744. doi:10.1001/jama.2023.1080.