Exposure to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with a reduced risk of cancer, including liver cancer, and overall mortality in patients with 

, according to findings from a recent study.

Results from the population-based cohort study of inpatients and outpatients with chronic liver diseases in Sweden suggest a significant risk reduction in overall cancer incidence and mortality with aspirin or NSAID use, even after taking comorbidities and the severity of the liver disease into account.

“To the best of our knowledge, this is the first study demonstrating a reduced cancer risk among patients with liver diseases exposed to aspirin and NSAIDs,” Knut Stokkeland, of the Stockholm Centre for Dependency Disorders and the department of clinical neuroscience at Karolinska Institutet in Sweden, and colleagues wrote.

According to the American Liver Foundation, more than 100 million people in the US have some form of liver disease which, left untreated, can lead to liver failure and liver cancer.

 Given the role that inflammation plays in the progression of chronic liver diseases, anti-inflammatory drugs may be beneficial for these patients, although aspirin and NSAIDs are currently widely viewed as harmful for patients with liver disease.

To explore the effects of exposure to anti-inflammatory drugs on the risk of adverse liver events, cancers, and mortality in patients with chronic liver diseases, investigators conducted a population-based cohort study of inpatients and outpatients between July 2005 and December 2020 using the Patient Register at the Swedish Board of Health and Welfare. They additionally searched the database for primary care in the central healthcare utilization data warehouse at the Stockholm Center for Health Data during the same period, merging the 2 registers to create a single primary cohort.

Investigators then collected data on all prescribed dispensed drugs from the Swedish Prescribed Drug Registry during the study period for aspirin; NSAIDs; antivirals; antibiotics; immunosuppressants; and glucocorticoids. Exposure to a drug was defined as ≥ 2 dispensations after the patient had been diagnosed with a liver disease. Exposure time was calculated from the first dispensation.

In total, the study cohort comprised 21,439 patients, the majority of whom had alcohol-associated liver disease (ALD; n = 9472), viral hepatitis (n = 7731), and autoimmune hepatitis (n = 493).

During 147,065.3 patient-years of follow-up, 10,279 (47.9%) patients died. Investigators noted more than half (51.1%) of patients with ALD died during the study period. Additionally, they pointed out the number of patients who developed any cancer was highest among those with primary biliary cholangitis (41.4%), and the greatest proportion of liver cancers was observed in patients with ALD (8.3%).

Results showed exposure to aspirin, NSAIDs, antivirals, and immunosuppressants was associated with a reduced risk for mortality, with the largest reduction in the crude hazard rate observed in patients exposed to NSAIDs (crude hazard ratio [cHR], 0.64; 95% CI, 0.61–0.68, 

 <.001). Of note, exposure to aspirin was also associated with a reduction in mortality risk (cHR, 0.92; 95% CI 0.88–0.97, 

 = 0.003), and reduced risks for all cancers and liver cancer were seen in patients exposed to aspirin (cHR, 0.73; 95% CI, 0.68–0.79; 

 <.001 for all cancers and cHR, 0.51; 95% CI, 043–0.59; 

In adjusted analyses, there was a reduced risk for all cancers when patients were exposed to aspirin (adjusted hazard ratio [aHR], 0.68; 95% CI, 0.63–0.73) and NSAIDs (aHR, 0.80; 95% CI, 0.75–0.86). Additionally, investigators observed a reduced risk of liver cancer in patients exposed to aspirin (aHR, 0.48; 95% CI, 0.41–0.57) and NSAIDs (aHR, 0.71; 95% CI, 0.62–0.82).

For mortality, results showed an overall risk reduction for patients exposed to NSAIDs (aHR, 0.68; 95% CI, 0.64–0.72) and a reduced risk for patients exposed to aspirin (aHR, 0.86; 95% CI, 0.82–0.91) after adjusting for comorbidities and severity of the liver disease.

“Whereas the observed risk reductions should be interpreted with caution, the results may inform future design of explorative clinical trials of aspirin or NSAIDs in selected patients with liver diseases,” investigators concluded.

 “Larger cohort studies could even explore if a dose-response relationship exists with regards to aspirin and NSAIDs and adverse events in patients with liver diseases.”

Stokkeland K, Söderberg-Löfdal K, Villner P, et al. Aspirin and NSAIDs are Associated With Reduced Cancer and Mortality Risk in Patients With Chronic Liver Diseases—A Swedish Cohort Study. 

American Liver Foundation. How Many People Have Liver Disease? September 11, 2023. Accessed February 10, 2025. https://liverfoundation.org/about-your-liver/facts-about-liver-disease/how-many-people-have-liver-disease/

Articles

A recent study suggests that aspirin and NSAIDs may reduce cancer risk and mortality in patients with chronic liver diseases. Conducted in Sweden, the study analyzed data from 21,439 patients with various liver conditions, including alcohol-associated liver disease and viral hepatitis. Results indicated significant reductions in overall cancer incidence and mortality with aspirin and NSAID use, even after adjusting for comorbidities and liver disease severity. These findings could guide future clinical trials to explore the potential benefits of these drugs in liver disease management.

Exposure to aspirin and NSAIDs was linked to a reduced risk of cancer incidence and overall mortality in patients with chronic liver diseases.

Aspirin, NSAID Use Linked to Lower Cancer, Mortality Risk in Chronic Liver Diseases

Results of the CAFETERIA trial suggest gradually escalating exposure to store-bought peanut butter could help desensitize children with 

, with this effect apparent even after discontinuing the treatment approach.

A trial of 73 children aged 4 to 14 years old lasting 18 months, results of the National Institutes of Health-funded research indicate those who consumed gradually increasing doses of store-bought peanut butter achieved greater and long-lasting rates of desensitization than their counterparts who avoided peanuts.

“Our findings open the gateway to personalized threshold-based treatments of food allergy and will encourage additional studies that delve deeper into peanut and other foods for this approach that might be a game-changer for the majority of people with food allergies,” said lead investigator Scott Sicherer, MD, director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai Kravis Children’s Hospital and chief of the Division of Allergy and Immunology in Mount Sinai’s Department of Pediatrics.

In recent years, the advent of new therapeutic approaches, including oral immunotherapy, have transformed the management of food allergy for many. However, as investigators note, pivotal trials supporting the approval of oral immunotherapies, such as peanut allergen powder-dnfp (Palforzia) and omalizumab (Xolair) were conducted among patient populations with low tolerance to food allergens.

For inclusion in the CAFETERIA trial, patients were required to be able to ingest at least 443 mg of peanut protein but less than 5043 mg. In contrast, the omalizumab pivotal trial had a maximum tolerance to peanut protein of 100 mg or less. The POSEIDON trial of peanut allergen powder-dnfp had a tolerance range of more than 3 mg to 300 mg or less and the PALISADE trial had a required tolerance of 100 mg or less.

“The research team recognized that more than half of people with peanut allergy can tolerate half a peanut or more, and thought that this group of people might be treatable if we took a different approach to peanut oral immunotherapy. We were thrilled to find that this treatment strategy was even more successful than we had anticipated,” said co-senior investigator Julie Wang, MD, professor of Pediatrics at the Icahn School of Medicine, clinical researcher at the Jaffe Food Allergy Institute.

In the CAFETERIA trial, 73 children aged 4 to 14 years old were randomized in a 1:1 to peanut oral immunotherapy using home-measured peanut butter or peanut avoidance. A total of 38 participants were randomized to the exposure group and 35 were randomized to the avoidance group. According to parent/guardian reporting, approximately 60% of the cohort was white, 19% were Asian, 1.4% were Black, and 22% were more than 1 race.

The primary outcome of interest was the difference between the treatment and avoidance groups in the percentage of children who tolerate a dose at least 2 steps greater than baseline or 9043 mg of peanut protein. Among those tolerating 9043 mg, a secondary analysis was performed to assess sustained unresponsiveness after 16 weeks of ad-lib ingestion followed by 8 weeks of abstinence.

Per trial protocol, all dose increases were performed under medical supervision.

Investigators highlighted there were 0 severe reactions among the peanut ingestion group during the study. Additionally, investigators also highlighted 0 participants from the peanut-ingestion group had severe reactions or needed 

 during home dosing and only one received epinephrine during a supervised dosing visit.

At the conclusion of the study, 84.2% of the peanut exposure group and 85.7% of the avoidance group participated in the primary outcome food challenge. The primary analysis revealed a 100% success rate for ingestion versus 21.0% for avoidance, with a between-group difference of 79.0 percentage points (95% CI, 64. To 93.5; 

 <.001). All 32 treated participants and 10% of peanut avoiders tolerated the 9043 mg test. In the intention-to-treat analysis, sustained unresponsiveness was observed in 68.4% of the ingestion group compared to just 8.6% of the avoidance group (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3).

“Children with high-threshold peanut allergy couldn’t participate in previous food allergy treatment trials, leaving them without opportunities to explore treatment options,” said  Jeanne Marrazzo, MD, MPH, director of the National Institute of Allergy and Infectious Diseases. “Today’s report focuses on this population and shows that a very safe and accessible form of therapy could be liberating for many of these children and their families.”

Sicherer SH, Bunyavanich S, Berin MC, et al. Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy. 

. Published online February 10, 2025. doi:10.1056/EVIDoa2400306

Mount Sinai Health System. Eating gradually increasing doses of store-bought peanut butter enables children with high-threshold allergy to safely consume peanuts. Mount Sinai Health System. February 10, 2025. Accessed February 10, 2025. https://www.mountsinai.org/about/newsroom/2025/eating-gradually-increasing-doses-of-store-bought-peanut-butter-enables-children-with-high-threshold-allergy-to-safely-consume-peanuts.

National Institutes of Health. Therapy helps peanut-allergic kids tolerate tablespoons of peanut butter. National Institutes of Health. February 10, 2025. Accessed February 10, 2025. https://www.nih.gov/news-events/news-releases/therapy-helps-peanut-allergic-kids-tolerate-tablespoons-peanut-butter.

Wood RA, Togias A, Sicherer SH, et al. Omalizumab for the Treatment of Multiple Food Allergies. 

. 2024;390(10):889-899. doi:10.1056/NEJMoa2312382

Du Toit G, Brown KR, Vereda A, et al. Oral Immunotherapy for Peanut Allergy in Children 1 to Less Than 4 Years of Age. 

. 2023;2(11):EVIDoa2300145. doi:10.1056/EVIDoa2300145

PALISADE Group of Clinical Investigators, Vickery BP, Vereda A, et al. AR101 Oral Immunotherapy for Peanut Allergy. 

. 2018;379(21):1991-2001. doi:10.1056/NEJMoa1812856

Data from the CAFETERIA trial provide insight into exposure vs avoidance strategies for high-threshold peanut allergy.

In Food Allergy, Exposure to Store-Bought Peanut Butter Bests Avoidance Strategies

Copper (Cu) and iron (Fe) are associated with 

 (FM) risk according to new research with trace elements, warranting further study.

“There is evidence suggesting that abnormalities in trace element metabolism may be associated with the development and progression of the disease.

 For example, Fe deficiency has been linked to fatigue and cognitive impairments in FM patients; zinc deficiency is associated with inflammatory responses and oxidative stress, both relevant to the pathophysiology of FM; and magnesium deficiency can lead to muscle pain and increased neural excitability, aligning with FM’s symptomatic pain. However, these associations are primarily based on cross-sectional or case-control studies, making it challenging to establish causality and potentially subject to confounding and reverse causation effects,” lead investigator Wenxing Zeng, First Clinical College of Guangzhou University of Chinese Medicine, and First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China, and colleagues wrote.

Zeng and colleagues analyzed trace elements using inverse-variance weighting (IVW), Mandelian randomization Egger, weighted median, weighted mode, and simple mode methods. They also used multivariable analysis to control for selenium as a potential confounder to evaluate the independent associations of Cu and Fe with FM risk. Using 2-sample MR analysis, they found a positive association between Cu and increased risk of FM (IVW: OR, 1.095 [95% CI, 1.015 -1.181]; 

= .018), and a negative association between Fe and FM risk (IVW: OR, 0.440 [95% CI, 0.233-0.834]; 

 = .011). The investigators found that these associations remained significant in the multivariable analysis and there were no other significant associations with other trace elements such as selenium and zinc.

“Our findings provide new insights for future research, particularly in exploring how Cu and Fe influence the onset and progression of FM. Future studies need to delve into the molecular level to reveal how these trace elements influence the pathological processes of FM through specific molecular pathways and signaling routes. This includes detailed studies on the impact of inflammatory mediators, oxidative stress markers, and neurotransmitter systems,” Zeng and colleagues wrote.

“Considering the potential interactions between genetic and environmental factors, future work should evaluate how genetic variations interact with factors like diet, lifestyle, and occupational exposures to affect individual susceptibility to FM. Large-scale epidemiological studies will help validate the associations between trace element status and FM risk and explore dose-response relationships. Comparative studies across different populations will assess the consistency of these associations across various ethnicities, genders, and age groups. Overall, future research will provide a deeper understanding, helping to develop new prevention and treatment strategies, and offer more targeted interventions for individuals at high risk for FM,” Zeng and colleagues concluded.

Other research recently found that people with fibromyalgia syndrome (FMS) had impaired bioenergetic health index (BHI), a proxy of mitochondrial function, which also had a slight correlation with pain.

 People with FM had a lower median BHI (−22.1%, 

REFERENCES
1. Zeng, W., Hu, M., Ma, L. et al. Copper and iron as unique trace elements linked to fibromyalgia risk. 

 15, 4019 (2025). https://doi.org/10.1038/s41598-025-86447-4

2. Chen, L., Min, J. & Wang, F. Copper homeostasis and cuproptosis in health and disease. 

 7 (1), 378. https://doi.org/10.1038/s41392-022-01229-y (2022)

3. Macchi C, Giachi A, Fichtner I, et al. Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. 

(2024): 14(30247). doi: 10.1038/s41598-024-81298-x

Recent research indicates a link between copper (Cu) and iron (Fe) levels and fibromyalgia (FM) risk. Cu is positively associated with increased FM risk, while Fe shows a negative association. These findings suggest that trace element metabolism abnormalities may contribute to FM development. The study utilized various statistical methods to control for confounders and confirmed the associations. Future research should explore molecular pathways and genetic-environmental interactions to better understand FM's pathophysiology. Additionally, impaired mitochondrial function in FM patients correlates with disease severity, highlighting potential therapeutic targets.

Copper had a positive association with FM risk and iron had a negative association.

Copper and Iron Associated With Fibromyalgia Risk

Credit: Beth Israel Deaconess Medical Center

 were 1.5-fold higher in adults aged ≥65 in the United States, compared with Denmark, with notable disparities by social risk factors, including income level, according to a recent cross-sectional study.

The study, involving nearly 60 million US adults and 2 million Danish adults, found the burden of myocardial infarction (MI) and heart failure (HF) hospitalizations significantly higher in the US, but ischemic stroke hospitalizations slightly lower, with mixed hospitalization-related mortality across all conditions.

“Our findings provided important public health insights regarding the burden of cardiovascular disease (CVD)–the leading cause of death globally–in 2 higher-income countries with distinct health systems,” wrote the investigative team, led by Rishi K. Wadhera, MD, MPP, MPhil, section of health policy & equity, Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center. “There are several potential reasons for the higher overall burden of cardiovascular hospitalizations that we observed in the US.”

Wadhera and colleagues set out to measure the burden of cardiovascular events in the US against other high-income countries with a distinct healthcare system, such as Denmark. The fragmented nature of US healthcare can create barriers to preventive care, including a lack of access to screen cardiometabolic risk factors in midlife, leading to greater events down the line.

Given the rising prevalence of cardiometabolic risk factors in US adults, social risk factors, including poverty and low educational attainment, are strongly linked to a greater CVD risk in later life. On the other hand, universal health systems in Denmark emphasize primary and preventive care services, which may allow for earlier diagnosis and treatment of CVDs.

For this analysis, the investigative team centered on individual-level data for adults ≥65 years in the US and Denmark from January 2021 to January 2022 to allow assessment of hospitalizations for acute CVDs, 30-day hospitalization-related mortality rates, and the impact of income-based inequities on these outcomes. Low income was defined as dual eligibility for Medicare and Medicaid in the US (~15% of the population) and the lowest 15th percentile of household income over the previous 3 years in Denmark.

The primary outcome of the analysis was annual age- and sex-standardized hospitalization rates per 1000 US and Danish adults, both overall and separately for MI, HF, and stroke. The secondary analysis focused on 30-day all-cause mortality rates after hospitalization in both countries.

A total of 58,614,110 US adults aged ≥65 (mean age, 74.6; 54.9% female) were identified for analysis, of whom 1,171,058 (2.0%) were hospitalized for a cardiovascular event. In Denmark, 1,176,542 adults aged ≥65 (mean age, 75.3 years; 53.9% female) were identified and 16,305 (1.4%) were hospitalized with a cardiovascular event.

Upon analysis, Wadhera and colleagues found overall age- and sex-standardized cardiovascular hospitalizations significantly higher in the US, compared with Denmark (risk ratio [RR], 1.50; 95% CI, 1.47–1.52). The difference remained significant for MI hospitalizations (RR, 1.56; 95% CI, 1.51–1.61) and HF hospitalizations (RR, 2.37; 95% CI, 2.31–2.43), but not ischemic stroke hospitalizations (RR, 0.90; 95% CI, 0.88–0.93).

Income analysis revealed US cardiovascular hospitalization rates more than 2-fold higher in low-income populations, compared with higher-income (RR, 2.38; 95% CI, 2.25–2.47) groups, and particularly for HF hospitalizations (RR, 2.76; 95% CI, 2.59–2.93). For Denmark, a smaller income-based gap was identified, with a slightly higher rate of cardiovascular hospitalizations in low-income groups (RR, 1.45; 95% CI, 1.39–1.50).

Further analysis showed 30-day all-cause mortality rates slightly elevated in the US, compared with Denmark (RR, 1.12; 95% CI, 1.06–1.17), particularly for MI (RR, 1.81; 95% CI, 1.61–2.05) and stroke (RR, 1.38; 95% CI, 1.25–1.54). However, HF-related mortality rates were lower in the US than in Denmark (RR, 0.79; 95% CI, 0.73–0.85), suggesting the potential for differences in acute care delivery.

“Although hospitalization rates were significantly higher in the US, 30-day mortality rates were significantly lower, which might reflect variation in the delivery of acute care between the 2 nations’ health systems as well as underlying differences in the severity of illness among those hospitalized with HF,” Wadhera and colleagues wrote.

Berg FH, Lassen MCH, Vaduganathan M, et al. Cardiovascular Hospitalizations Among Older Adults in the US and Denmark. JAMA Cardiol. Published online February 05, 2025. doi:10.1001/jamacardio.2024.5303

McClellan M, Brown N, Califf RM, Warner JJ. Call to Action: Urgent Challenges in Cardiovascular Disease: A Presidential Advisory From the American Heart Association. Circulation. 2019;139(9):e44-e54. doi:10.1161/CIR.0000000000000652

Aggarwal R, Yeh RW, Joynt Maddox KE, Wadhera RK. Cardiovascular Risk Factor Prevalence, Treatment, and Control in US Adults Aged 20 to 44 Years, 2009 to March 2020. JAMA. 2023;329(11):899-909. doi:10.1001/jama.2023.2307

A cross-sectional study compared cardiovascular hospitalizations in adults aged ≥65 in the US and Denmark, revealing a 1.5-fold higher rate in the US. The study highlighted disparities linked to social risk factors, such as income. The US showed higher hospitalization rates for myocardial infarction and heart failure, but lower for ischemic stroke. Income-based disparities were more pronounced in the US. Despite higher hospitalization rates, the US had lower 30-day mortality for heart failure, suggesting differences in acute care delivery and illness severity between the two countries.

Cardiovascular hospitalization rates were higher in the US than in Denmark, driven by a significant increase in heart failure and myocardial infarction hospitalizations.

Cardiovascular Hospitalizations Burden the US More than Denmark 

A new study showed anaphylaxis following a non-COVID-19 vaccination is rare but varies by vaccine type.

“The results of this meta-analysis provide critical insights into the low overall incidence of anaphylactic events associated with vaccines,” wrote investigators, led by Flavia Pennisi, PhD, from the National Programme in One Health Approaches to Infectious Diseases and Life Science Research at the University of Pavia in Italy. “The significantly higher event rate observed for influenza vaccines compared to other vaccine types, particularly under the random-effects model, suggests potential variability in study populations, reporting standards, or underlying risk factors.”

Vaccines may result in anaphylaxis, a rare, life-threatening allergic reaction causing fatal airway, respiratory, or circulatory complications. The incidence of vaccine-related anaphylaxis ranges from 50 to 20,000 cases per 100,000 person-years, with fatal outcomes occurring in approximately 0.05 cases per 100,000 people annually.

 Research on vaccine-related anaphylaxis expanded with the introduction of the COVID-19 vaccine.

Despite this, data on anaphylaxis incidence from non-COVID-19 vaccines in adults remains limited. Investigators conducted a systemic review and meta-analysis to estimate the incidence of anaphylaxis following various non-COVID-19 vaccinations.

They searched PubMed, Embase, Scopus, and Web of Science, selecting 37 studies with adults aged ≥ 18 years (n = 206,855,261) for the systemic review. Only 22 studies were included in the meta-analysis, as the remaining 15 lacked anaphylactic shock case reports. Studies were conducted in America (n = 28), Europe (n = 5), Asia (n = 2), and Africa (n = 1), with 1 conducted across 105 sites in North America and Europe.

Most studies examined influenza vaccines (n = 15), followed by vaccines for pneumococcal (n = 8), tetanus and diphtheria or tetanus toxoid (Td/dTap) (n = 7), herpes zoster virus (n = 6), hepatitis B (n = 5), human papillomavirus (n = 4), yellow fever (n = 3), hepatitis A (n = 2), Japanese encephalitis (n = 2), meningococcal (n = 2), varicella (n = 1), rabies (n = 1), rotavirus (n = 1), and tick-borne encephalitis (n = 1). The analysis identified 262 anaphylactic cases, with 153 linked to influenza vaccines, 38 to herpes zoster virus vaccines, 29 to yellow fever vaccines, and 22 to pneumococcal vaccines.

Vaccines associated with fewer reactions included the ones for measles, mumps, and rubella (MMR) (n = 13), hepB-alum (n = 2), human papillomavirus (n = 2), meningococcal disease group B (n = 1), hepatitis A (n = 1), and Japanese encephalitis (n = 1).

Influenza vaccines may have accounted for the highest absolute number of anaphylaxis cases, but when considering sample size, the yellow fever vaccine demonstrated the greatest rate of anaphylaxis at 2.1 per 100,000 participants. Conversely, the td/Tdap vaccine had the lowest anaphylaxis rate of 0.0001 per 100,000 participants. Pneumococcal vaccines had the second lowest anaphylaxis rate: 0.9 per 100,000 participants.

The time to onset of anaphylaxis ranged from minutes to 14 days. Most cases were moderate to severe and treated with epinephrine (n = 8) alongside antihistamines and corticosteroids (n = 9).

The meta-analysis showed a low incidence of anaphylactic shock across various vaccines: -10.45 (95% confidence interval [CI], -12.09 to -8.82; P < .001, corresponding to a rate of approximately 0.57 events per 100,000 participants (95% CI, 0.49 to 0.68). The random-effects model showed the anaphylaxis incidence following a vaccine: 2.91 events per 100,000 participants (95%; confidence interval [CI], 0.56 to 14.73); P < .001).

The sensitivity analysis demonstrated a greater anaphylaxis prevalence for the vaccines of influenza (11.2 events per 100,000 subjects; 95% CI, 0.4 to 310) and hepatitis (19.05 events per 100,000 subjects; 95% CI, 0.08 to 4733.35), as well as vulnerable populations (48 events per 100,000 subjects; 95% CI, 4 to 631). Pneumococcal vaccines had the lowest event rates (0.122 events per 100,000 individuals).

“Monitoring patients beyond the immediate post-vaccination period, especially those with complex medical histories, can help ensure that delayed reactions are appropriately managed and correctly classified,” investigators wrote. “The rapid progression of symptoms in severe cases makes timely intervention critical. These observations underscore the current recommendations that any provider administering vaccines should have emergency protocols and supplies on hand, including epinephrine, should a patient develop anaphylaxis.”

Pennisi F, D'Amelio AC, Cuciniello R, Borlini S, Mirzaian L, Ricciardi GE, Minerva M, Gianfredi V, Signorelli C. Post-Vaccination Anaphylaxis in Adults: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2025 Jan 4;13(1):37. doi: 10.3390/vaccines13010037. PMID: 39852816; PMCID: PMC11769139.

Lieberman, P.; Camargo, C.A., Jr.; Bohlke, K.; Jick, H.; Miller, R.L.; Sheikh, A.; Simons, F.E. Epidemiology of anaphylaxis: Findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. 

Salsone, M.; Signorelli, C.; Oldani, A.; Alberti, V.F.; Castronovo, V.; Mazzitelli, S.; Minerva, M.; Ferini-Strambi, L. NEURO-COVAX: An Italian Population-Based Study of Neurological Complications after COVID-19 Vaccinations. 

A recent study highlights the rarity of anaphylaxis following non-COVID-19 vaccinations, with variability across vaccine types. Influenza vaccines showed a higher incidence of anaphylactic events compared to others, potentially due to differences in study populations or risk factors. The meta-analysis included 22 studies, identifying 262 anaphylactic cases, with influenza vaccines accounting for the majority. Yellow fever vaccines had the highest rate of anaphylaxis per participant, while Td/Tdap vaccines had the lowest. The study emphasizes the importance of monitoring patients post-vaccination and having emergency protocols in place.

An analysis found anaphylaxis following non-COVID vaccines is rare, with greater rates for yellow fever and influenza vaccines.

Anaphylaxis Following Non-COVID Vaccines Are Rare but Vary by Type

 is a severe, potentially life-threatening hypersensitivity reaction that requires prompt recognition and intervention. While clinical diagnosis remains paramount, recent advancements have highlighted the role of specific biomarkers in confirming and assessing anaphylaxis. 

The 2023 update to the AAAAI’s Practice Parameter on Anaphylaxis provides updated clinical recommendations on recognizing anaphylaxis across diverse clinical presentations and discusses the utility of biomarkers such as tryptase in aiding diagnosis. This review served as a high-level summary of the 2023 practice parameter with evidence uncovered since the 2015 practice parameter. 

Some of the updates in the practice parameters focused on new and evolving diagnoses of anaphylaxis, the rules for defining elevated tryptase levels, and the recognition of signs and symptoms for infants and toddlers. The writing committee suggested that risk factors for anaphylaxis should be assessed on a case-by-case basis, with patient counseling and shared decision-making essential to support patients’ treatment decisions.

In our first quiz focused on these updates, the 

 editorial staff aims to assess your understanding of anaphylaxis diagnostic criteria, the role of laboratory markers, and how these updates influence clinical practice.

A) A patient with hereditary α-tryptasemia

B) A patient with a documented peanut allergy but no prior anaphylaxis history

C) A patient with seasonal allergic rhinitis

D) A patient with chronic urticaria but no history of anaphylaxis

Editor’s note: This quiz was composed with the assistance of AI tools.

Wang J, Lieberman JA, Wallace DV, Waserman S, Golden DBK. Anaphylaxis in Practice: A Guide to the 2023 Practice Parameter Update. 

. 2024;12(9):2325-2336. doi:10.1016/j.jaip.2024.06.036


The 2023 update to the AAAAI's Practice Parameter on Anaphylaxis emphasizes the importance of prompt recognition and intervention in anaphylaxis, incorporating recent advancements in biomarker utilization, such as tryptase, for diagnosis. The update provides revised clinical recommendations, focusing on new diagnoses, elevated tryptase level definitions, and symptom recognition in infants and toddlers. It underscores the necessity of individualized risk assessment, patient counseling, and shared decision-making in treatment planning. The HCPLive editorial staff has developed a quiz to evaluate understanding of these updates and their impact on clinical practice.

Test your knowledge of the 2023 Anaphylaxis Update from the Joint Task Force on Practice Parameters, focusing on diagnoses and biomarkers!

Clinical Quiz: Diagnosis and Biomarkers in Anaphylaxis

Long-Term VIVID-2 Data for Mirikizumab in Crohn’s Disease, with Edward Barnes, MD, MPH

Findings from the VIVID-2 open-label extension study of mirikizumab-mrkz (Omvoh) in patients with moderately to severely active 

 are highlighting the IL-23p19 antagonist’s impact on long-term clinical and endoscopic outcomes.

The data come just weeks after the US Food and Drug Administration (FDA) approved mirikizumab for the treatment of CD, building upon its previous indication for 

. The decision for its use in CD is based on positive results from the phase 3 VIVID-1 study in adults who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, and/or biologics.

Historically, patients with CD have had limited treatment options, starting with the 1998 FDA approval of the first anti-tumor necrosis factor (TNF) therapy, infliximab.

“We had sort of a revolutionary era in 1998 when we saw the introduction of an anti-TNF therapy, but then we had this large period of time between 1998 and 2014 where we only had anti-TNF therapies,” Edward Barnes, MD, MPH, an associate professor of medicine in the division of gastroenterology and hepatology and co-director of the Multidisciplinary Inflammatory Bowel Diseases Center at the University of North Carolina at Chapel Hill, told 

. “In the past couple of years, we’ve seen this explosion of different mechanisms of action.”

However, Barnes called attention to the “therapeutic ceiling” that still exists for CD and the ongoing need to treat patients earlier, more effectively, and with the right mechanism of action. He noted having mirikizumab as an option for patients “changes the landscape” by providing clinicians with another potential first-line treatment option beyond anti-TNFs, allowing them to stratify patients based on which therapy may be a better fit for them.

New data from the VIVID-2 open-label extension study build upon findings from VIVID-1 used to support mirikizumab’s approval in CD. In the trial, 92.9% of patients who were in clinical remission at 1 year in VIVID-1 maintained clinical remission at 2 years.

Among patients treated in VIVID-2, 87.6% maintained endoscopic response. Among patients who were in endoscopic remission at 1 year of treatment in VIVID-1, 78.6% maintained endoscopic remission at 2 years.

Results also showed 60.8% of patients who were not in clinical remission by CDAI at 1 year gained clinical remission during the second year of treatment. For those who were not in endoscopic remission at 1 year, 35.4% gained endoscopic remission during the second year of treatment.

“For any decision that we make [for patients], it's going to be really important to know that drug is effective, safe, and it's going to work to treat their disease,” Barnes said. “That's why I think having mirikizumab approved and having some of the results that we're here talking about at Crohn’s and Colitis Congress is really exciting.”

Editors’ note: Barnes has relevant disclosures with AbbVie, Bristol-Meyers Squibb, Lilly, and Target RWE.

Brooks A. VIVID-2: Mirikizumab (Omvoh) Shows Long-Term Efficacy for Crohn’s Disease. 

. February 7, 2025. Accessed February 10, 2025. 

https://www.hcplive.com/view/vivid-2-mirikizumab-omvoh-shows-long-term-efficacy-crohn-disease

Brooks A. FDA Approves Mirikizumab (Omvoh) for Crohn’s Disease. 

. January 15, 2025. Accessed February 10, 2025. 

https://www.hcplive.com/view/fda-approves-mirikizumab-omvoh-for-crohn-disease

Mirikizumab, an IL-23p19 antagonist, has shown promising long-term clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease (CD), as evidenced by the VIVID-2 open-label extension study. Following its recent FDA approval for CD, mirikizumab offers a new treatment option beyond anti-TNF therapies, addressing the therapeutic ceiling in CD management. The study demonstrated high rates of sustained clinical and endoscopic remission over two years, highlighting its potential as a first-line treatment. This advancement marks a significant shift in the therapeutic landscape for CD.

Barnes explains the significance of having mirikizumab as a treatment option for Crohn’s disease and reviews new VIVID-2 open-label extension data.

An announcement by Nektar Therapeutics highlights the new decision by the 

 to grant Fast Track designation to rezpegaldesleukin for the treatment of adult and pediatric patients with moderate-to-severe 

Respegaldesleukin is an investigational biologic option which was formulated to stimulate the proliferation of regulatory T cells by targeting the interleukin (IL)-2 receptor complex, potentially leading to restored immune system balance. The drug was designed to do this for patients with atopic dermatitis, an inflammatory condition that impacts approximately 30 million individuals within the US.

“We are pleased that rezpegaldesleukin has been designated a Fast Track product," Jonathan Zalevsky, PhD, Nektar’s senior vice president and Chief Research and Development Officer, said in a statement. "Rezpegaldesleukin has the potential to address a significant unmet need for the millions of patients living with moderate-to-severe atopic dermatitis.”

Prior to the February 10 announcement of its designation, rezpegaldesleukin’s efficacy in treating atopic dermatitis was evaluated in the phase 2b REZOLVE-AD clinical trial.

 In the REZOLVE-AD phase 2b analysis, the team enrolled 398 individuals with moderate-to-severe atopic dermatitis who had not previously been treated with biologic options or with JAK inhibitors. Patients with atopic dermatitis were recruited across approximately 110 sites across the world.

The REZOLVE-AD investigators randomly assigned their trial participants to be given 1 of 3 different dose regimens of rezpegaldesleukin or provided with a placebo during a 16-week induction phase. The team then re-randomized subjects who met a specified improvement threshold in their Eczema Area and Severity Index (EASI) score to be provided maintenance therapy at their original dose level, either once in a given month or once every 3 months.

The investigative team’s primary endpoint in REZOLVE-AD was the mean improvement in EASI score after the 16-week induction period. In terms of secondary endpoints assessed in the study, examples include the proportion of subjects reporting at least a 75% EASI score improvement (EASI-75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, and experiencing a 4-point or more reduction on the Itch Numeric Rating Scale (NRS).

A Body Surface Area (BSA) involvement of at least 10%, a minimum EASI score of 16.0, and a vIGA-AD score of 3 at the screening and randomization time points had been required for participants to enroll.

The announcement by Nektar highlighted rapid improvements that had been observed in exploratory disease outcomes during the 12-week induction treatment phase of a phase 1b study.

 They also noted improvements for at least 36 weeks following medication cessation, highlighting proof-of-concept in the drug’s indication.

“We remain on track to announce topline data from the induction period of our Phase 2b REZOLVE-AD study in the second quarter of this year,” Zalevsky said in a statement. “This designation will now allow us to collaborate closely with the agency on the design of the registrational program for rezpegaldesleukin once we've completed Phase 2.”

Nektar Therapeutics Receives Fast Track Designation for Rezpegaldesleukin for the Treatment of Moderate-to-Severe Atopic Dermatitis. Nektar Therapeutics. February 10, 2025. https://www.prnewswire.com/news-releases/nektar-therapeutics-receives-fast-track-designation-for-rezpegaldesleukin-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-302371995.html.

Silverberg, J.I., Rosmarin, D., Chovatiya, R. et al. The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials. Nat Commun 15, 9230 (2024). https://doi.org/10.1038/s41467-024-53384-1.

Rezpegaldesleukin, an investigational biologic targeting the IL-2 receptor complex, has received Fast Track designation from the FDA for treating moderate-to-severe atopic dermatitis in patients aged 12 and older. This designation follows promising results from the phase 2b REZOLVE-AD trial, which evaluated its efficacy in 398 patients. The trial's primary endpoint was the mean improvement in EASI score after a 16-week induction phase. The drug demonstrated rapid and sustained improvements in exploratory outcomes, supporting its potential to address unmet needs in atopic dermatitis treatment.

The drug given this designation, known as rezpegaldesleukin, is indicated for adult and pediatric patients aged 12 years and older with atopic dermatitis.

FDA Grants Fast Track Designation to Rezpegaldesleukin for Atopic Dermatitis

Nerandomilast significantly improved forced vital capacity (FVC) in people with progressive pulmonary fibrosis (PPF) compared to placebo, meeting the primary endpoint in the phase 3 FIBRONEER-ILD trial.

According to their February 10, 2025 announcement, Boehringer Ingelheim plans to submit a new drug application for nerandomilast for treating PPF to the FDA as well as applications to other regulatory agencies around the world.

“The positive FIBRONEER™-ILD topline result shows the potential of nerandomilast in PPF. The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges,” Shashank Deshpande, Head of Human Pharma and Member of the Board of Managing Directors at Boehringer Ingelheim, said in a statement.

 “The recent milestones of the FIBRONEER™ trial program underscore our commitment to transforming the lives of patients with this debilitating disease, and are a testament to Boehringer Ingelheim's position at the forefront of pulmonary fibrosis research.”

Nerandomilast is an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B). FIBRONEER-ILD’s primary endpoint was the absolute change from baseline in FVC in milliliters at week 52 versus placebo in patients receiving nerandomilast. The trial demonstrates continued safety and tolerability of nerandomilast which is comparable to phase 2 data of the therapy in idiopathic pulmonary fibrosis and an overall adverse event profile comparable to those seen in the placebo group.

 Boehringer expects to share full efficacy and safety data from FIBRONEER-ILD in the second quarter of 2025.

The FIBRONEER-ILD trial treated patients with PPF with either oral nerandomilast 9 mg or 18 mg, or placebo, twice-daily, over at least 52 weeks. The 18 mg dose was informed by phase 2 study data, and the 9 mg dose was added to evaluate the benefit-risk profile at a lower dose. Secondary endpoints included time to the first occurrence of any of the components of the composite endpoint: time to first acute interstitial lung disease (ILD) exacerbation; first hospitalization for respiratory cause; or death (whichever occurs first) over the duration of the trial. The trial was conducted in more than 1178 patients across 400 locations in 40 countries.

FIBRONEER-ILD is the second Phase 3 trial in which the nerandomilast has met its primary endpoint, following the FIBRONEER-IPF (NCT05321069) trial in the FIBRONEER program.

 The trials had the same primary and secondary endpoints, but differed in study populations of IPF and PPF.

REFERENCES
1. Boehringer’s nerandomilast meets primary endpoint in Phase III study FIBRONEER™-ILD, in progressive pulmonary fibrosis. News release. Boehringer. February 10, 2025. https://www.globenewswire.com/news-release/2025/02/10/3023409/0/en/Boehringer-s-nerandomilast-meets-primary-endpoint-in-Phase-III-study-FIBRONEER-ILD-in-progressive-pulmonary-fibrosis.html

2. Richeldi L, et al. (2022) Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. In:

3. Boehringer Ingelheim (2024) A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Idiopathic Pulmonary Fibrosis (IPF). Accessed January 2025. Available at: https://clinicaltrials.gov/study/NCT05321069

Nerandomilast, an investigational PDE4B inhibitor, significantly improved forced vital capacity in patients with progressive pulmonary fibrosis (PPF) in the phase 3 FIBRONEER-ILD trial, meeting its primary endpoint. Boehringer Ingelheim plans to submit a new drug application to the FDA and other global regulatory agencies. The trial demonstrated nerandomilast's safety and tolerability, with adverse events comparable to placebo. Conducted in over 1,178 patients across 40 countries, the trial also evaluated secondary endpoints like time to first acute ILD exacerbation, hospitalization, or death. Full efficacy and safety data are expected in 2025.

Boehringer plans to soon submit a new drug application for nerandomilast for treating PPF to the FDA.

Nerandomilast Meets Primary Endpoint in Improving FVC in Progressive Pulmonary Fibrosis

 has accepted the Biologics License Application (BLA) for lerodalcibep targeting reductions in 

low-density lipoprotein cholesterol (LDL-C)

 levels in a patient population with or at high risk for 

atherosclerotic cardiovascular disease (ASCVD)

Announced by LIB Therapeutics Inc. on February 10, 2025, the FDA set a Prescription Drug User Fee Act (PDUFA) action date of December 12, 2025, with no plans to hold an advisory committee meeting. The BLA for lerodalcibep was supported by 5 global Phase 3 registrational studies in the LIBerate program.

“There remains a large unmet need among millions of patients with CVD, or at high cardiovascular risk, including the 30 million people with inherited high cholesterol, who are unable to achieve currently recommended guideline-directed goals for LDL-C with current oral therapies,” said Evan Stein, MD, co-founder and chief operating and scientific officer of LIB, in a statement. “Lerodalcibep has demonstrated robust and sustained long-term LDL-C-lowering, enabling the vast majority of patients to achieve these more stringent lower LDL-C targets with excellent safety and adherence across clinical trials.”

A novel, adnectin-based, small protein-binding, third-generation PCSK9 inhibitor, LIB Therapeutics developed lerodalcibep as a single small-volume, subcutaneous injection alternative to approved PCSK9 drugs. Citing its unique patient-friendly, once-monthly self-administration, the company indicated that lerodalcibep does not require refrigeration at home or during travel.

The BLA for lerodalcibep was submitted to the FDA in December 2024, based on positive results from the global Phase 3 LIBerate program. These trials included 2900 patients with CVD or at very high or very high risk for CVD, including patients with heterozygous (HeFH) and those aged >10 years with homozygous familial hypercholesterolemia (HoFH). Across key registration-enabling, placebo-controlled trials, patients received once-monthly lerodalcibep for up to 52 weeks.

Results from the Phase 3 LIBERATE-HeFH trial showed mean placebo-adjusted LDL-C reductions of 65% with lerodalcibep at 24 weeks. Approximately 68% of patients achieved LDL-C reductions ≥50%, meeting European Society of Cardiology (ESC) guideline-recommended targets.

 In the LIBerate-High Risk (HR) trial, lerodalcibep achieved 56% greater reductions in LDL-C levels than placebo across 1 year in patients with or at very high risk for CVD.

From these trials, a population of 1468 patients with or at very high risk for CVD and 703 patients with HeFH continued into the 72-week LIBerate open-label extension (OLE) trial

Patients with or at very high risk for CVD maintained > 60% reductions (P <.0001) in LDL-C from baseline throughout the additional 72 weeks of open-label extension lerodalcibep dosing, without signs of attenuation. Those with HeFH maintained 50% to 53% (P<0.0001), with 72 to 76 mg/dL absolute, reductions in LDL-C across the 72 weeks with no signals of attenuation.

LIB Therapeutics announced that, following the FDA BLA filing, they anticipate submitting Marketing Authorization Application to the European Medicines Agency (EMA) in Q2 2025.

“Lerodalcibep is a potential best-in-class PCSK9 inhibitor with a once-monthly, single small-volume subcutaneous dose, combined with long ambient stability not requiring refrigeration at home or in travel, offering a more patient-firendly treatment option to achieve the new lower LDL-C goals,” said David Cory, chief executive officer of LIB Therapeutics, in a statement.

 “The LIB operating team is now focused on Lerodalcibep US commercial launch preparation.”

Lib Therapeutics announces FDA acceptance of biologics license application for Lerodalcibep to lower LDL-cholesterol across broad patient population. Business Wire. February 10, 2025. Accessed February 10, 2025. https://www.businesswire.com/news/home/20250210806330/en/LIB-Therapeutics-Announces-FDA-Acceptance-of-Biologics-License-Application-for-Lerodalcibep-to-Lower-LDL-Cholesterol-Across-Broad-Patient-Population.

Iapoce C. Lib Therapeutics submits bla for Lerodalcibep targeting reductions in LDL-C. HCP Live. December 19, 2024. Accessed February 10, 2025. https://www.hcplive.com/view/lib-therapeutics-submits-bla-for-lerodalcibep-targeting-reduction-in-ldl-c.

Campbell P. Lerodalcibep shows promise for HeFH in phase 3 liberate-hefh trial. HCP Live. August 30, 2023. Accessed December 19, 2024. https://www.hcplive.com/view/lerodalcibep-shows-promise-for-hefh-in-phase-3-liberate-hefh-trial

LIB Therapeutics Announce Positive Results from Lerodalcibep 72-Week Open-Label Extension Studies at American Heart Association 2024. LIB Therapeutics. November 18, 2024. Accessed December 19, 2024. https://cdn.prod.website-files.com/61e62faab82c326a4b4e92af/673bd0313462d3b1c033ef5e_2024%201118%20LIB%20AHA%202024%20PR.pdf.

The FDA has accepted the Biologics License Application for lerodalcibep, a novel PCSK9 inhibitor developed by LIB Therapeutics, targeting LDL-C reduction in patients with or at high risk for ASCVD and primary hyperlipidemia. Supported by five global Phase 3 studies, lerodalcibep demonstrated significant LDL-C reductions and safety. It offers a patient-friendly, once-monthly subcutaneous injection without refrigeration needs. LIB Therapeutics plans to submit a Marketing Authorization Application to the EMA in 2025, with a US commercial launch preparation underway.

Announced by LIB Therapeutics Inc., the agency has set a PDUFA target action date of December 12, 2025.

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