Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

Credit: University of Southern California

 (Krystexxa; Amgen) was not found to put patients with gout at a higher risk of thromboembolic (TE) and cardiovascular (CV) events, according to a new post-hoc analysis of multiple trials assessing the therapy.

“In these trials, the proportion of patients experiencing gout flares increased during the first month of pegloticase therapy but rapidly and progressively declined to nearly 0% over 12 months of therapy. Although CV safety signals were not identified in pegloticase clinical trials, the demonstrated relationship between gout flares and CV/TE events has raised the important question of whether or not pegloticase treatment increases these events in uncontrolled gout patients,” first author Orrin M. Troum, MD, Division of Rheumatology, University of Southern California Keck School of Medicine and Providence Saint John’s Health Center, and colleagues wrote.

Troum and colleagues conducted a post hoc analysis of pooled data from 4 trials examining treatment-emergent gout flare and CV/TE events in patients with uncontrolled gout, including 2 phase 3 trials (NCT00325195), the MIRROR open-label trial (NCT03635957), and the MIRROR randomized controlled trial (NCT03994731). Participants in these studies received pegloticase (8 mg) every 2 (all trials) or 4 weeks (phase 3 trials). This analysis included data from the first 24 weeks of therapy. Some MIRROR patients received methotrexate (15 mg/week) as co-therapy. Investigators considered the high-risk window for CV/TE events as 120 days following flare onset based on prior studies.

The investigators found that 5/328 (1.5%) patients experienced at least 1 CV/TE event during pegloticase treatment, including 3/244 (1.2%) patients who received on-label (biweekly) dosing (35.4 events/1000 person-years). All events occurred within the high-risk, 120-day gout flare exposure window.

“In conclusion, treatment with pegloticase did not increase the frequency of CV/TE events and the overall incidence of CV/TE events reported in this post hoc analysis was similar to that in the general gout population. Further, all identified CV/TE events occurred within 120 days after gout flare onset, a window of higher risk determined by a prior study. Given that gout flare occurrence is lower in patients who maintain SU levels <6 mg/dL, ULT use in a treat-to-target SU approach is not only an important component of gout management, but could play a role in maintaining long-term health in patients with gout,” Troum and colleagues concluded.

Troum previously presented findings from the phase 4 AGILE study investigating shortened, 1-hour infusion times of pegloticase in combination with methotrexate at November 2024’s American College of Rheumatology (ACR) Convergence. The data demonstrated that shortened infusions of pegloticase was well-tolerated with preserved efficacy in patients with uncontrolled gout, demonstrating a promising option for reducing treatment burden.

“Pegloticase is currently approved to be given over a 2-hour period and this often has an impact… on [patients’] daily lives, if this is an every 2 week therapy for at least 6 to 12 months,” Troum told 

Troum OM, Duong M, Obermeyer K, Padnick-Silver L, LaMoreaux B. Treatment-Emergent Major Adverse Cardiovascular and Thromboembolic Events were Infrequent During Clinical Trials of Pegloticase. 

. Published online January 10, 2025. keaf017. doi: 10.1093/rheumatology/keaf017

Troum O, Botson J, Fang F, et al. Safety, Tolerability and Efficacy of Pegloticase Administered with a Shorter Infusion Duration in Subjects with Uncontrolled Gout Receiving Methotrexate: Primary Findings of the AGILE Open-label Trial. Presented at: Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract 2012.

Articles

Pegloticase, used for treating uncontrolled gout, does not increase the risk of thromboembolic and cardiovascular events, as shown in a post-hoc analysis of multiple trials. The analysis included data from four trials, with a focus on the first 24 weeks of therapy. Only 1.5% of patients experienced cardiovascular or thromboembolic events, all occurring within a 120-day high-risk window post-gout flare onset. Maintaining serum urate levels below 6 mg/dL is crucial for reducing gout flares and associated risks. Shortened infusion times of pegloticase with methotrexate were well-tolerated and effective.

A post-hoc analysis evaluated pooled data from 4 trials of pegloticase.

Pegloticase Does Not Increase Risk of CV/TE Events in People With Gout

New research has found that cold fomentation was more effective than hot fomentation in relieving pain and improving mobility in patients with a gout flare, while hot fomentation often worsened symptoms.

“Heat therapy, such as hot saline fomentation, can exacerbate the inflammatory response during a gout attack by increasing blood flow to the affected area, leading to further swelling and discomfort. Heat may also contribute to the solubilization of uric acid crystals, potentially promoting their deposition in joints, thereby worsening symptoms during the acute phase of gout,” Shivam Mehra, Mehra Hospital and Research Institute, Lucknow, Uttar Pradesh, India, and colleagues wrote.

Mehra and colleagues conducted a randomized controlled trial including 2,400 patients with gout randomized to receive hot fomentation (38°C–42°C) or cold fomentation (5°C–10°C) applied twice daily for 20 minutes over 5 days, alongside standard care. They measured pain intensity using the visual analog scale (VAS), while joint circumference, range of motion, and patient satisfaction were recorded at baseline, day 3, and day 5, and used statistical analysis to compare outcomes between the 2 groups.

The investigators found that cold fomentation significantly reduced pain intensity on VAS by 68% by day 5 compared to hot fomentation, which yielded a 26% reduction on VAS (

 <.001). The cold group also experienced a decrease in joint swelling by 25% versus 5% in the hot group and had greater improvements in joint mobility (average increase of 15° vs. 5°, 

 <.01). Notably, 35% of the hot group experienced flare-ups, compared to only 2% in the cold group (

 <.001). The cold group had a higher rate of satisfaction (85%) than the hot group (30%).

“These results strongly suggest that cold fomentation should be the preferred thermal therapy in the management of gout flares, while hot fomentation should be avoided due to the risk of worsening the inflammatory response. Clinicians should consider these findings when advising patients on appropriate thermal therapies for gout management,” Mehra and colleagues concluded.

In other relevant news related to gout management, recent research found that while rheumatologists self-report high adherence to the 2020 American College of Rheumatology (ACR) Guideline for Gout Management, there are gaps in knowledge and adherence, particularly around dosing of treatment regimens.

The mean overall stated adherence score was 11.5 (maximum 15), and the mean overall stated agreement score was 7.7 (maximum 14). Schlesinger and colleagues found that less experienced rheumatologists with up to 8 years of experience (n = 49) were more likely to report adherence (mean stated adherence score, 12.3) to individual ACR recommendations than those with more experience (n = 152; mean stated adherence score, 11.3; 

Guidelines for initiating urate-lowering therapy (ULT) were reportedly followed by 78% of rheumatologists, with 89% likely to prescribe allopurinol as a first-line ULT. Dosing recommendations were not highly adhered to, with 43% adhering to febuxostat dosing recommendations and 39% adhering to allopurinol dosing recommendations. Furthermore, rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares.

These findings are notable as proper ULT administration has been shown to improve outcomes in people with gout in multiple ways.

Mehra S, Mehra K, Mehra NK, Kale SY, Manchanda BV. Data Insights on the Risks of Local Heat and Massage in Gouty Arthritis Treatment. 

2025;15(1):260-265. doi:10.13107/jocr.2025.v15.i01.5194

Schlesinger N, Pillinger MH, Lipsky PE. Knowledge of and Stated Adherence to the 2020 American College of Rheumatology Guideline for Gout Management: Results of a Survey of US Rheumatologists. 

 2025, 52 (1) 77-86; doi: 10.3899/jrheum.2023-0981

Heat therapy often worsened symptoms in a randomized controlled trial.

Research Confirms Cold Therapy Benefits During Gout Flares

New research has found that cyclic adenosine monophosphate (cAMP) is highly elevated in the blood of people with asthma, enabling diagnosis and possibly severity determination with a simple blood test.

"What we discovered is a specific transporter, a protein on the membrane of airway smooth muscle cells, allows cAMP to leak into the blood," senior investigator Reynold Panettieri, MD, vice chancellor for Translational Medicine and Science at Rutgers University, said in a statement.

 "For decades, we believed that an enzyme called phosphodiesterase was the critical factor in decreasing cAMP. We now refute that and say this transporter simply leaks it out."

Panettieri and colleagues analyzed blood samples from 87 patients with asthma, 39 of which had severe asthma, and 273 participants without asthma. They found that cAMP levels were consistently higher in the blood of asthma patients by up to 1000 times and correlated with disease severity. The findings may offer a new tool for monitoring patient conditions.

"It's really difficult to do lung function tests in kids under the age of 5," Panettieri said.

 "However, our data suggests that if you just did a pinprick, maybe you could diagnose kids who can’t access or do lung function tests."

Looking at serum cAMP levels between severity groups, the investigators found no significant difference between severe asthma and nonsevere asthma serum cAMP levels but each asthma group showed significantly higher cAMP levels (adjusted 

 < .00001) than the non-asthma group. They did not find any significant associations between serum cAMP levels and clinical traits of asthma, however, serum cAMP levels did arithmetically increase with the number of inhaled corticosteroids puffs and controllers used and, in the nonsevere asthma group, with the increases of post-bronchodilator lung function.

"If you look at city dwellers, about 1 in 15 people has asthma," Panettieri added.

 "It’s incredibly common — the number one reason kids go to the emergency room."

Panettieri and colleagues are working to develop a point-of-care test for doctors' offices after initial attempts at a simple lateral flow device were not sensitive enough.

"We would anticipate maybe in the next 6 months, we'll have nailed the fidelity of it, get it into our intellectual property and patent the test itself, and then in a year to 2, it could become available," Panettieri said.

The investigators concluded by noting that further studies are needed to explore associations between serum cAMP levels and bronchodilator or treatment responses by asthma severity; ABCC1 expression and activity in health and disease, including specific cell types of origin; and whether these physiological outcomes and clinical phenotypes are affected by variations in ABCC1 genotypes in a large cohort of patients with and without asthma.

"Every disease we study or treat is not one disease," Panettieri added.

 "There are different aspects and attributes within a disease entity."

An SS, Cao G, Ahn K, et al. Serum cAMP levels are increased in patients with asthma. 

Published online January 7, 2025. doi: 10.1172/JCI186937

Scientists Discover Potential Blood Test for Asthma Diagnosis and Severity. News release. Rutgers University. January 15, 2025. https://www.rutgers.edu/news/scientists-discover-potential-blood-test-asthma-diagnosis-and-severity

Recent research indicates that cyclic adenosine monophosphate (cAMP) levels are significantly elevated in the blood of asthma patients, potentially enabling diagnosis and severity assessment through a simple blood test. A specific transporter protein on airway smooth muscle cells allows cAMP to leak into the bloodstream, challenging previous beliefs about phosphodiesterase's role. Although cAMP levels correlate with asthma presence, they do not significantly differ between severe and nonsevere cases. Further studies are needed to explore cAMP's relationship with treatment responses and genetic variations in asthma patients.

Current asthma diagnosis requires specialized breathing tests that can be challenging for young children. 

Elevated Serum cAMP Findings May Allow Asthma Diagnosis by Blood Test

Biologic treatment for rheumatoid arthritis (RA) or 

 did not negatively affect fertility in women, according to a recent study published by Elsevier in 

“Although used frequently, knowledge regarding the possible effects of bDMARDs on aspects of fertility remains limited… Women with RA have been reported to have fewer offspring than intended, experience prolonged time to conception, and have a higher incidence of sub-fertility compared to the general population

,” lead investigator Einat Haikin Herzberger, MD, Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, and School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Israel, and colleagues wrote.

Herzberger and colleagues conducted a retrospective cohort study based on an electronic health record (EHR) that included 4517 women with RA and 1415 women with PsA between the ages of 18 and 40 years old. Biologics in use included tumor necrosis factor inhibitors, anti-CD-20 monoclonal antibodies, interleukin blockers and T-cell inhibitors. The study’s main outcome measure was positive pregnancy test rate and secondary outcome measures were pregnancy attempts and use of in vitro fertilization (IVF).

Participants with RA and PsA had similar mean ages at diagnosis (respectively, 30.7; standard deviation [SD], 6.3 vs. 30.9; SD, 6; 

 = .260) and at biologic initiation (respectively, 34.2; SD, 8 vs. 34.2; SD, 7.5 years; 

The investigators found that fertility was higher before diagnosis in both groups, with rates of positive beta-hCG tests decreasing from 84.5% to 63.6% in the RA group and from 87.1% to 61.4% in the PsA group (both 

 <.01 for both comparisons). Initiating biologics did not negatively affect beta-hCG test rate, with women with PsA showing a trend toward an increased likelihood of achieving pregnancy after initiating biologic treatment (

 =.05), while the rates remained stable in women with RA.

Additionally, Herzberger and colleagues found that beta hCG testing increased in both groups after initiation of biological treatments (RA, 

 =.07). Comparing women with RA initiating biologics compared with women with RA or PsA who did not initiate biologics, crude rates of positive beta-hCG were 229/431 (53.1%), 1120/1743 (64.3%), and 318/492 (64.6%) respectively, with no significant differences between groups.

Use of fertility medications before diagnosis was about 8.35% in the RA group and 8.4% in the PsA group (both 

 >.5) and dropped after diagnosis but before exposure to approximately 4% in both groups (

 >.5) but recovered to 8.3% in the RA group and 7% in the PsA group (

 >.5). IVF rate in the RA group decreased after exposure (

 <.01) but was not significantly different in the PsA group (

“The large cohort analyzed in this database study provides novel, reassuring data regarding spontaneous and medicated fertility in women with RA and PsA exposed to biological medications. Further studies to differentiate between sub-categories of bDMARDs, as well as data on live births are warranted,” Herzberger and colleagues concluded.

Herzberger EH, Hornik-Lurie T, Levi Y, et al. The effect of biological treatment on female fertility: A cohort study of women with rheumatoid arthritis and psoriatic arthritis. 

Published online December 20, 2024. doi: 10.1016/j.semarthrit.2024.152608

Brouwer J, Hazes JM, Laven JS, Dolhain RJ. Fertility in women with rheumatoid arthritis: influence of disease activity and medication. 

Biologic treatments for rheumatoid arthritis (RA) and psoriatic arthritis (PsA) do not adversely impact fertility in women, according to a retrospective cohort study. The study analyzed 4517 women with RA and 1415 with PsA, focusing on pregnancy test rates and fertility treatments. Results indicated that biologic initiation did not negatively affect fertility, with PsA patients showing a trend towards increased pregnancy likelihood. Fertility medication use decreased post-diagnosis but recovered after biologic exposure. The study suggests further research on specific biologic sub-categories and live birth outcomes is needed.