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The study findings published in BMJ Open have demonstrated the frequency and degree of alcohol consumption to be the risk factors for hyperuricemia (HUA), especially in males. Moderate drinking was also observed to be a risk factor for HUA among men in the study.

“Different from the benefits of moderate drinking found in other research, HUA risk among moderate drinkers is 1.23 times than that of never drinkers among those in males,” the researchers reported. “HUA risk is higher for those who usually drink alcohol l than for those who never drink alcohol among the total population.”

“The risk of HUA caused by harmful drinking is the highest, which is 1.81 times that of never-drinkers among the total population and 2.13 times than that of never-drinkers among males,” they added, “However, among females, HUA risk was not found to change with drinking.”

Hyperuricaemia is becoming a common chronic disease with a worldwide economic and health burden. Considering the widespread consumption of alcohol in the world, some clinicians’ review of dietary advice for HUA and gout patients shows that the most general advice is complete avoidance or restriction of alcohol intake, in which this suggested frequency is usually beyond weight loss.

The influence of drinking frequency and degree on hyperuricaemia needs further exploration. Therefore, Siyu Chen, School of Public Health, Chongqing Medical University, Chongqing, China, and colleagues aimed to investigate the relationship between alcohol consumption and hyperuricaemia based on a large population.

The researchers enrolled 20,833 participants aged 30–79 years in the China Multi-Ethnic Cohort, Chongqing region. The serum levels of fasting blood glucose, uric acid, and blood lipids were tested. A standardised questionnaire was used to collect basic demographic statistics such as gender, age, education level, marital status, detailed information on alcohol consumption, and family annual income.

The study led to the following findings:

• After controlling for potential confounders, compared with participants who never consumed alcohol, participants who drank 3–5 days per week had the highest HUA risk (OR: 1.51) and those who drank alcohol harmfully had the highest risk of HUA (OR: 1.81).
• Those who drank moderately had no significant association with the risk of HUA. However, among men, compared with participants who never consumed alcohol, those who drank moderately were also a risk factor for HUA (OR: 1.23) and those who drank alcohol harmfully had the highest risk of HUA (OR: 2.13).
• Compared with participants who drank alcohol moderately, the OR for those who drank alcohol harmfully had the highest risk of HUA was 1.88, and the corresponding OR for each level increment in the degree of alcohol consumption was 1.22.
• Among men, compared with participants who drank alcohol moderately, those who drank alcohol harmfully had the highest risk of HUA (OR: 1.93), and the corresponding OR for each level increment in the degree of alcohol consumption was 1.24.

The study demonstrated a positive relation between the frequency and degree of alcohol consumption and the risk of hyperuricemia. This positive connection was obvious among men, but weak among women. Moderate drinking was also revealed to be a risk factor for HUA among men in the study.

“There is a need for further interventional and prospective research to verify the causal relationship and clarify the specific mechanism,” they concluded.

Reference:

Chen S, Ding R, Tang X, et alAssociation between alcohol consumption and risk of hyperuricaemia among adults: a large cross-sectional study in Chongqing, ChinaBMJ Open 2023;13:e074697. doi: 10.1136/bmjopen-2023-074697

The study, published in Pediatric Obesity revealed that CB leptin is positively associated with childhood and neonatal adiposity and child leptin levels, independent of maternal body mass index (BMI) and maternal hyperglycemia.

“The study’s major finding was the significant positive relationship between cord blood leptin and adiposity later in childhood, which has not been consistently observed in previous studies,” the researchers reported.

Leptin is a pleiotropic hormone that is mainly produced by adipose tissue, but also by skeletal muscle, the liver and the placenta. Cord blood leptin is positively associated with adiposity at birth, but there is no clarity on its association with child adiposity. Therefore, Sean DeLacey, Northwestern University, Chicago, Illinois, USA, and colleagues aimed to expand upon current evidence and describe the relationship between CB leptin and later childhood adiposity.

They hypothesized that CB leptin is positively associated with peripubertal childhood adiposity measures including childhood leptin.

For this purpose, the researchers measured leptin in 986 CB and 931 childhood stored samples from a prospective birth cohort. Adiposity measures were collected at birth and the mean age was 11.5 years.

The associations between log-transformed CB leptin and neonatal and childhood adiposity measures were evaluated as continuous and categorical variables, respectively using linear and logistic regression analyses.

The study revealed the following findings:

• CB leptin was positively associated with neonatal and childhood adiposity.
• Childhood associations were attenuated when adjusted for maternal BMI and glucose but remained statistically significant for childhood body fat percentage (β = 1.15%), body fat mass (β = 0.69 kg), sum of skin-folds (β = 1.77 mm), overweight/obesity (OR = 1.21), log-transformed child serum leptin (β = 0.13), obesity (OR = 1.31) and body fat percentage >85th percentile (OR = 1.38).
• Positive associations between newborn adiposity measures and CB leptin confirmed previous reports.

“We found that CB leptin was positively associated with neonatal fat mass, child leptin levels and multiple adiposity measures in the peripubertal age period,” the researchers wrote. “The magnitude of this association was small but was robust to adjustment for maternal pregnancy factors.”

“Future studies can work upon current knowledge by elucidating the mechanism by which higher neonatal leptin may affect future adiposity, including continuing to evaluate leptin and leptin receptor gene expression as it relates to future adiposity,” they concluded.

Reference:

DeLacey, S., Gurra, M., Arzu, J., Lowe, L. P., Lowe, W. L., Scholtens, D. M., & Josefson, J. L. Leptin and adiposity measures from birth to later childhood: Findings from the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study. Pediatric Obesity, e13087. https://doi.org/10.1111/ijpo.13087

ZORYVE foam provides rapid disease clearance and significant reduction in itch, with nearly 80% of individuals achieving the primary efficacy endpoint of IGA Success and just over 50% of individuals reaching complete clearance at Week 8 in the STRATUM trial. ZORYVE is a once-daily steroid-free foam and the first drug approved for seborrheic dermatitis with a new mechanism of action in over two decades.

“We know from dermatology clinicians and those living with seborrheic dermatitis that there has been a real struggle with disease clearance and treatment adherence due to lack of efficacy, difficulty treating certain body areas, inconvenient treatment regimens, and concerns about safety with long-term use,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “ZORYVE foam is a once-daily, steroid-free topical treatment that can be used anywhere on the body, including hair-bearing areas, with no limitation on duration of use. We are proud to deliver meaningful innovation through this approval of ZORYVE foam, and to offer a new topical treatment that effectively clears and controls the disease and can simplify its management for the millions of adults and adolescents living with seborrheic dermatitis.”

Seborrheic dermatitis affects more than 10 million people in the United States, and is a common, chronic, and recurrent inflammatory skin disease that causes red patches covered with large, greasy, flaking yellow-gray scales, and persistent itch. In individuals with darker skin tones, inflamed areas may not appear red, but instead can appear pink, slightly purple, or lighter in color than the surrounding skin. It occurs most often in areas of the body with oil-producing (sebaceous) glands, including the scalp, face (especially on the nose, eyebrows, ears, and eyelids), upper chest, and back. Hair-bearing areas make applying topicals like creams, gels, and ointments difficult.

“In the STRATUM trial, ZORYVE foam provided rapid disease clearance as early as Week 2 and significant itch relief in as little as 48 hours. In addition, almost 80% of patients achieved treatment success at Week 8. While multiple factors contribute to seborrheic dermatitis, inflammation and skin barrier dysfunction play key roles. ZORYVE has been shown to effectively reduce the signs of inflammation, redness, and scaling in patients with seborrheic dermatitis, and with its unique formulation, ZORYVE foam effectively delivers the drug without disrupting the skin barrier and has been shown to be safe and tolerable. ZORYVE foam is thus ideally formulated, having the potential to become the new standard of care for seborrheic dermatitis treatment,” said Andrew Blauvelt, MD, MBA, clinical investigator at Oregon Medical Research Center, and investigator on the STRATUM trial.

Beyond the appearance and irritation of physical symptoms, seborrheic dermatitis is associated with a decrease in quality of life and may negatively affect emotional well-being, self-esteem, and day-to-day life, including sleep and work. People with seborrheic dermatitis, and especially adolescents and school-age children, may suffer from social stigma, negative self-image, and low self-esteem associated with very visible skin diseases like seborrheic dermatitis.

“Approximately 10 million people in the United States have seborrheic dermatitis, but until today, there have been limited treatment options. We are thrilled with this FDA approval and are excited to bring to market a new, highly effective steroid-free topical formulation that can be used anywhere on the body,” said Frank Watanabe, president and CEO of Arcutis. “Our commercial team is ready and poised to launch ZORYVE foam very soon, and we are committed to ensuring affordable access to ZORYVE foam to those who may benefit from this novel treatment.”

Arcutis intends to make ZORYVE foam widely available via key wholesaler and dermatology pharmacy channels as a new treatment option by the end of January 2024. The Company is dedicated to responsible pricing and affordable access to therapy. The ZORYVE® Direct Program helps patients access their prescribed Arcutis medication. For patients with seborrheic dermatitis who have been prescribed ZORYVE, this patient support program helps patients navigate the payer process, assists patients with adherence, and includes the ZORYVE Direct Savings Card Program, which can help reduce out-of-pocket costs for eligible commercially insured patients.† Arcutis will also continue to offer the Arcutis CaresTM patient assistance program (PAP) that provides ZORYVE at no cost for financially eligible patients who are uninsured or underinsured.‡

Management will host a conference call on Monday, December 18 at 8:30 a.m. EST. A live webcast of the call and presentation material will be available on the “Events” section of the Company’s Investor website. An archived version of the webcast will be available on the Arcutis website after the call.

ZORYVE Foam Clinical Data

The approval is supported by positive results from Arcutis’ Phase 2 and pivotal Phase 3 trials in seborrheic dermatitis. The STudy of Roflumilast foam Applied Topically for the redUction of seborrheic derMatitis (STRATUM) and the Phase 2 (Trial 203) were parallel group, double-blind, vehicle-controlled studies evaluating the safety and efficacy of ZORYVE foam 0.3% in seborrheic dermatitis. Together the two studies enrolled 683 adults and adolescents ages 9 years and older.

The STRATUM study met its primary endpoint, with nearly 80% of ZORYVE foam treated individuals reaching Investigator Global Assessment (IGA) Success rate at Week 8 (79.5% ZORYVE foam vs 58.0% vehicle; P<0.0001). In Trial 203, 73% of individuals treated with ZORYVE foam achieved IGA Success (73.1% ZORYVE foam vs 40.8% vehicle; P<0.0001.) IGA Success was defined as an IGA score of “Clear” (0) or “Almost Clear” (1), plus a 2-grade IGA score improvement from baseline at Week 8.

Improvement with ZORYVE foam was seen early, with roflumilast demonstrating a statistically significant improvement compared to vehicle on IGA Success at Week 2, the first timepoint assessed in STRATUM. In addition, 50.6% of individuals in the ZORYVE foam treated arm reached complete clearance (IGA=0) at Week 8.

The STRATUM study also demonstrated statistically significant improvement over vehicle on all secondary endpoints, including itch, scaling, and erythema (redness). More than 60% of individuals achieved a ≥4-point reduction in itch at Week 8 as measured by Worst Itch-Numerical Rating Score (62.8% roflumilast foam vs 40.6% vehicle; P=0.0001), and significant improvements in itch were also reported at Week 2 and Week 4. Individuals treated with ZORYVE foam reported a 28% improvement in itch from baseline in 48 hours (compared to 13% on vehicle nominal P=0.0024).

In addition, more than 50% of individuals treated with ZORYVE foam achieved an erythema (redness) score of 0, and more than 50% achieved a scaling score of 0, at Week 8. Treatment with ZORYVE foam demonstrated a significantly larger improvement in patient reported outcomes as early as Week 2 as measured through Dermatology Life Quality Index (DLQI), with improvements maintained through Week 8.

ZORYVE foam was well-tolerated with a favorable safety and tolerability profile during up to 52 weeks of treatment. Incidence of Treatment Emergent Adverse Events (TEAEs) was low and similar between active treatment and vehicle, with most TEAEs assessed as mild to moderate severity. There were no treatment-related Serious Adverse Events (SAEs). Overall, the most common adverse reactions occurring in ≥1% of subjects in the combined Phase 2 and Phase 3 study populations were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).

About ZORYVE®

ZORYVE (roflumilast) topical foam, 0.3%, is indicated for treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. Another formulation of ZORYVE, roflumilast cream 0.3%, is approved by the FDA for the topical treatment of plaque psoriasis in individuals 6 years of age and older. Both ZORYVE foam and cream are topical formulations of roflumilast, a highly potent and selective phosphodiesterase-4 (PDE4) inhibitor. PDE4 is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. It is an established target in dermatology.

However, this approval is subject to a condition that the Phase-Ib part of the study will not be applicable in India.

This came after the drug major AstraZeneca presented Phase1b/III Clinical Study Protocol no. D361DC00001.

This Phase Ib/III study aims to evaluate the efficacy, safety, and degree of the added benefit of capivasertib combined with CDK4/6i and fulvestrant in participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer.

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2, and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function, and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA).