Efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of 

metabolic dysfunction–associated steatohepatitis (MASH)

, failed to significantly reduce fibrosis without worsening of MASH at 36 weeks in a phase 2b trial.

Data from the SYMMETRY trial were published in the 

 and show that although the trial missed its primary endpoint for fibrosis reduction without worsening of MASH, the 50 mg dose of efruxifermin may have possible benefit on fibrosis reduction at 96 weeks. Notably, efruxifermin also appeared to be associated with improvements in MASH-related histologic findings, noninvasive markers of liver injury and fibrosis, and markers of glucose and lipid metabolism.

“Trials of therapies that target metabolic dysregulation, inflammation, and fibrosis in patients with MASH cirrhosis thus far have not resulted in a reduction in fibrosis,” Mazen Noureddin, MD, MHSc, a professor of medicine and transplant hepatologist at Houston Methodist Hospital, and principal investigator for the SYMMETRY study, and colleagues wrote.

An FGF21 analogue in development for the treatment of advanced fibrosis and cirrhosis caused by MASH, efruxifermin features a bivalent configuration consisting of 2 modified human FGF21 polypeptides fused to each fragment crystallizable domain of homodimeric human immunoglobulin G1, which extends both pharmacokinetic and pharmacodynamic half-lives.

SYMMETRY was a phase 2b, randomized, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Puerto Rico, and Mexico. It enrolled patients 18-75 years of age with liver histologic features consistent with MASH and compensated cirrhosis, defined as stage 4 fibrosis with a Child–Pugh score of 5 or 6. Patients also had type 2 diabetes or 2 components of metabolic syndrome.

Participants were randomly assigned in a 1:1:1 ratio to receive 28 mg or 50 mg of efruxifermin or matching placebo, administered subcutaneously once weekly. Randomization was stratified according to whether they had type 2 diabetes and their MASH diagnosis, biopsy-confirmed MASH or cryptogenic cirrhosis attributed to MASH.

The primary outcome was a reduction of ≥ 1 stage of fibrosis without worsening of MASH at week 36. Selected secondary endpoints were a reduction in fibrosis without a worsening of MASH at week 96 and MASH resolution at weeks 36 and 96.

A total of 181 patients underwent randomization and received ≥ 1 dose of efruxifermin or placebo. Of these patients, liver biopsy was performed in 154 patients at 36 weeks and in 134 patients at 96 weeks.

Preliminary topline week 96 results from SYMMETRY announced earlier in 2025 showed 39% of patients with baseline and week 96 biopsies who were treated with efruxifermin 50 mg experienced reversal of cirrhosis with no worsening of MASH, compared to 15% for placebo (

= .009). In the intent-to-treat population with all missing week 96 biopsies treated as failures, 29% of patients in the 50 mg efruxifermin group experienced reversal of cirrhosis with no worsening of MASH, compared to approximately 12% in the placebo group (

at 36 weeks, a reduction in fibrosis without worsening of MASH occurred in 13% of the placebo group and 18% of the 28 mg efruxifermin group (difference from placebo after adjustment for stratification factors, 3 percentage points; 95% confidence interval [CI], –11 to 17; 

= .62), and in 19% of the 50 mg efruxifermin group (difference from placebo, 4 percentage points; 95% CI, –10 to 18; 

At week 96, a reduction in fibrosis without worsening of MASH occurred in 11% of the placebo group, in 21% of the 28 mg efruxifermin group (difference from placebo, 10 percentage points; 95% CI, –4 to 24), and in 29% of the 50-mg efruxifermin group (difference from placebo, 16 percentage points; 95% CI, 2 to 30).

In an analysis involving the 134 patients for whom liver-biopsy data were available at week 96 without imputation of missing data, a reduction in fibrosis without MASH worsening was observed in 29% of the 28 mg efruxifermin group, 39% of the 50 mg efruxifermin, and 15% of the placebo group. In an exploratory analysis involving patients who had a primary-outcome response at weeks 36 and 96, investigators noted most of those in the efruxifermin groups who had a response at week 36 sustained their response at week 96. Additionally, some patients without a response at week 36 had a response by week 96, particularly in the 50-mg dose group.

Comparison of the proportion of patients with a fibrosis reduction at week 36 and week 96 in the pre-specified analysis of patients with baseline and week 96 biopsies, showed more than a doubling of placebo-adjusted treatment effect for the EFX 50mg group, from 10% to 24%, highlighting the importance of longer treatment with efruxifermin for patients with compensated cirrhosis.

Efruxifermin was also associated with improvements in noninvasive markers of fibrosis, including ELF test scores, liver-stiffness measurements, and Pro-C3 levels, as well as levels of lipids — triglycerides, non–high-density-lipoprotein (HDL) cholesterol, and HDL cholesterol — and markers of insulin sensitivity.

Adverse events were reported by 99% of the patients who received efruxifermin and 97% of those who received placebo. Adverse events that were more common with efruxifermin than with placebo were primarily gastrointestinal as well as administration-site reactions, and most adverse events were mild or moderate in severity.

“In this trial, efruxifermin did not have significant benefit regarding a reduction in fibrosis without a worsening of MASH at week 36. However, the trial duration of 96 weeks enabled identification of possible treatment effects that were not apparent at week 36,” investigators concluded.

 “Longer studies in diverse populations will be necessary to evaluate clinical outcomes, safety, and generalizability of the findings and to assess benefits of longer-term treatment.”

Noureddin M, Rinella ME, Chalasani NP, et al. Efruxifermin in Compensated Liver Cirrhosis Caused by MASH. 

Brooks A. Efruxifermin Reverses MASH Compensated Cirrhosis in Phase 2b SYMMETRY Study. 

. January 27, 2025. Accessed May 9, 2025. 

https://www.hcplive.com/view/efruxifermin-reverses-mash-compensated-cirrhosis-phase-2b-symmetry-study

Akero Therapeutics. Akero Therapeutics Presents Week 96 Results from Phase 2b SYMMETRY Clinical Trial of Efruxifermin in Patients with Compensated Cirrhosis Caused by MASH Showing Fibrosis Improvement without Worsening of MASH at the EASL Congress 2025. May 9, 2025. Accessed May 9, 2025. 

https://ir.akerotx.com/news-releases/news-release-details/akero-therapeutics-presents-week-96-results-phase-2b-symmetry 

Articles

Efruxifermin, a bivalent FGF21 analogue, was evaluated in a phase 2b trial for its efficacy in treating MASH-related fibrosis. The trial did not meet its primary endpoint of fibrosis reduction without worsening MASH at 36 weeks. However, at 96 weeks, the 50 mg dose showed potential benefits in fibrosis reduction and MASH-related histologic improvements. The trial highlighted the need for longer studies to assess the long-term efficacy and safety of efruxifermin. Adverse events were mostly mild to moderate, with gastrointestinal issues being more common in the treatment group.

Use of efruxifermin did not result in a significant reduction in fibrosis without worsening of MASH at week 36 compared with placebo in the phase 2b SYMMETRY trial.

Efruxifermin Shows Potential for Fibrosis Reduction in Phase 2b MASH Cirrhosis Trial

New findings support adalimumab biosimilar interchangeability and the practice of non-medical switches between such biosimilars for patients with 

, with the most commonly registered treatment discontinuation reason being a loss of effect.

These findings represent the conclusion of research conducted by such investigators as Ole Krogh-Jensen, from the Department of Dermatology and Allergy at Copenhagen University Hospital in Denmark. Krogh-Jensen and colleagues highlighted that, while previous research has pointed to a lack of effect on treatment persistence with transitioning from an originator biologic to a biosimilar, there had been limited data on the implications of undergoing multiple switches between various biosimilars.

The investigative team, based in Denmark, highlighted that the country's prescribing policies are based on cost, with requirements pointing to mandatory non-medical switching between adalimumab biosimilars whenever a lower-priced product is determined to be the preferred option.

“Since November 2018, several switches have occurred, from originator to GP2017 (Hyrimoz) to ABP 501 (Amgevita), back to GP2017 (Hyrimoz),” Krogh-Jensen and coauthors wrote.

 “This setup gives a distinctive real-world setting for assessing the consequences of multiple non-medical switches between biosimilars.”

Individuals deemed eligible to be participants included

 those with diagnoses of psoriasis at Copenhagen University Hospital—Herlev and Gentofte who had also been given an adalimumab therapeutic for at least 6 months before a required switch. The investigative team grouped the subjects based on the initial adalimumab product implemented.

Specifically, they separated them into the originator cohort (up to 3 switches), those in the GP2017 cohort (up to 2 switches), and the ABP 501 cohort (only a single switch). The main outcome that the team assessed in these participants was discontinuation of treatment within 6 months after the non-medical switch.

There were 182 patients in total who Krogh-Jensen et al involved in their analysis, with 61 individuals in the originator arm, 67 in the GP2017 arm, and 54 in the ABP 501 arm. They noted that 68.1% were male and that the subjects had a mean age of 48.3 years (±14.8).

Among all of the study cohorts, it was reported that therapy discontinuation took place within 6 months after the switch ranged from 0% - 8.2%. The highest rate of discontinuiation that the investigative team observed took place following the initial switch from the originator to GP2017.

They added that the lowest rate had been seen following the third switch in the originator cohort, specifically from ABP 501 to GP2017. Among the reasons given for cessation, the loss of therapeutic effect was the most commonly reported one. The investigators highlighted that 2 subjects stopped treatment as a result of adverse events, though subsequent remission was attained upon resuming the originator biologic.

Prior data on a variety of biosimilar switches were noted by the team to be sparse. A phase 3 clinical trial they pointed to, looking at switches to GP2017, indicated that multiple switches between the originator and GP2017 did not significantly raise patients' risk of psoriasis flares between Weeks 17 - 51 when comparing individuals who shifted between products with those who remained on the same drug.

Aligning with certain other research highlighted by the coauthors, a lack of elevated risk of therapy discontinuation was observed with multiple non-medical switches compared to the expected discontinuation rate for those who maintained a consistent treatment regimen. Krogh-Jensen and colleagues' data, suggesting that the initial change from originator to GP2017 carries the highest discontinuation risk, could result from increased uncertainty or hesitancy among individuals when first switching from an originator to a biosimilar.

Variations in injection devices, excipients, or formulation volumes may result in reactions at injection sites. The investigative team suggest that while this conclusion was not observed in this analysis specifically, have been attributed to 37% of adverse events related to non-medical switching in other research.

“In conclusion, this study's findings support the notion of biosimilar interchangeability and the practice of non-medical switches between adalimumab products,” the investigators concluded.

Krogh-Jensen O, Schwarz CW, Kaur-Knudsen D, et al (2025). Real-world experience of multiple switches between adalimumab biosimilars in patients with psoriasis. J Eur Acad Dermatol Venereol. 

Cohen AD, Vender R, Naldi L, Kalb RE, Torres T, Rajagopalan M, et al. Biosimilars for the treatment of patients with psoriasis: a consensus statement from the biosimilar working Group of the International Psoriasis Council. JAAD Int. 2020; 1(2): 224–230.

Research supports the interchangeability of adalimumab biosimilars and non-medical switches for psoriasis patients, with loss of effect being the primary reason for treatment discontinuation. The study, conducted in Denmark, involved 182 patients and assessed treatment discontinuation within six months of switching biosimilars. Findings indicated that the highest discontinuation rate occurred after the initial switch from the originator to GP2017, while the lowest was after the third switch. The study suggests that multiple non-medical switches do not significantly increase the risk of therapy discontinuation or psoriasis flares.

These findings support the conclusion that switching between adalimumab biosimilars largely maintains efficacy for patients with psoriasis.

Study Supports Adalimumab Biosimilar Interchangeability for Patients with Psoriasis

, also known as food intolerances, are extremely common, affecting roughly 1 out of every 5 people.

 Despite this prevalence, diagnosis and treatment of food sensitivity is a significant challenge.

The current standard of care employs a broad elimination diet that then systemically re-introduces foods in a guess-and-check manner. This can be a lengthy and frustrating process for patients, and the success of this approach has not been sufficiently validated. Here, we’ll review the preliminary report of a clinical trial employing a new silicon-based peptide microarray to accurately diagnose and treat food sensitivities with improved precision.

Food sensitivities are notoriously difficult to diagnose. Unlike food allergies that cause a more rapid and acute anaphylactic response, the symptoms of food sensitivities appear much more gradually.

Symptoms slowly manifest several hours or even days later, meaning that several meals may have been consumed before symptoms begin to occur. This can make it challenging for both patients and healthcare providers to identify the dietary component causing issues. Further complicating the picture are the variety of symptoms, both gastrointestinal (GI) and extra-GI, that are associated with food sensitivity, including abdominal pain, bloating, joint pain, dermatitis, and more. When left untreated, more serious complications can arise from the chronic inflammation caused by regular intake of the offending food.

Unfortunately, the current approach to diagnosis relies heavily on the process of elimination.

 Appropriately identifying food sensitivity often occurs only after excluding other diseases with overlapping clinical manifestations.

The clinical gold standard for confirmation and treatment of food sensitivity relies on broad elimination diet. Foods are slowly reintroduced one at a time to determine which ingredient (or ingredients) are causing problems. Patients struggle to adhere to this strict elimination diet, and the process can be incredibly time-consuming, highlighting the need for a better approach.

A recent clinical trial explored a novel approach to identifying and addressing food sensitivities based on their immunological roots.

 While food allergies are driven by Immunoglobulin E (IgE), food sensitivity is mediated by Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibody responses.

This molecular understanding of food sensitivity forms the basis of a new silicone-based peptide microarray assay able to accurately detect and identify IgA and IgG antibodies against 262 food antigens. Importantly, this microarray screens antibody epitopes at both the protein and peptide level, capturing a more complete picture of a patient’s food sensitivities. This blood-based assay, designed by Vibrant Wellness, was used in this study to identify food sensitivities for 52 participants experiencing GI symptoms and guided the creation of individualized elimination diets for the cohort.

Participants followed their personalized elimination diets for 4 weeks, and the severity of their symptoms was ranked on both the Food Sensitivity- Symptom Severity Scale (FS-SSS) and Global Improvement Scale (FS-GIS). An overwhelming majority of patients reported statistically significant improvements in their symptoms after a month on their tailored diets.

Self-reported symptoms improved with the median FS-SSS score dropping from 19.5 down to 6 by the end of the trial. Physician observations matched the self-assessment, with 84.17% of participants demonstrating improved health scores on the FS-GIS.

These improvements corresponded with improved antibody titers for food sensitivity as well. Using the silicone-based microarray assay, the research team measured a reduction in IgG levels in 96% of patients following the trial, as well as reduced IgA titers in 84% of study participants.

Patients need a faster, more efficient approach to food sensitivity symptom relief that current practices can’t provide. By harnessing our understanding of the immunological drivers of this condition, serological assays can be designed that definitively diagnose food sensitivities and allow healthcare teams to curate diets that will reduce IgA and IgG responses. Medicine shouldn’t rely on guesswork, and this study shows that a more data-driven path to addressing food sensitivities is possible.

Tuck CJ, Biesiekierski JR, Schmid-Grendelmeier P, Pohl D. Food Intolerances. Nutrients. 2019 Jul 22;11(7):1684. doi: 10.3390/nu11071684. PMID: 31336652; PMCID: PMC6682924.

Vora A, Vance D, Alnouri G, Sataloff RT. Food Sensitivity and Laryngopharyngeal Reflux: Preliminary Observations. J Voice. 2021 May;35(3):497.e5-497.e7. doi: 10.1016/j.jvoice.2019.09.005. Epub 2019 Nov 1. PMID: 31685326.

Hari Krishnan Krishnamurthy, Michelle Pereira, Vasanth Jayaraman et al. Personalized Food Elimination Diet: A Clinical Trial based on Food sensitivity assessment, 19 June 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-4596789/v1]

Velikova, Tsvetelina & Kukov, Alexander & Georgieva, Viktoriya & Peruhova, Milena & Yurukova, Nonka & Michova, Antoaneta & Marinova, Tsanka & Mizgova, Gergana & Terzieva, Velislava & Zhelezova, Galina & Altankova, Iskra & Ivanova, Ludmila. (2018). METHODS FOR DETECTION OF FOOD INTOLERANCE. 1. 106-119.

Food sensitivities affect a significant portion of the population, yet their diagnosis and treatment remain challenging. Traditional methods rely on elimination diets, which are time-consuming and often ineffective. A recent clinical trial introduced a novel silicon-based peptide microarray assay that identifies food sensitivities by detecting IgA and IgG antibodies. This approach allows for personalized elimination diets, leading to significant symptom improvement in patients. The study highlights the potential of data-driven interventions to provide more accurate diagnoses and effective treatments for food sensitivities, moving beyond the limitations of current practices.

Discover an approach to diagnosing food sensitivities, offering personalized diets and significant symptom relief through testing methods.

Eliminating Guesswork for Food Sensitivity

Phase 2 LUNA Trial Results for Ixo-vec to Treat Neovascular AMD with Dante Pieramici, MD

2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting

, Dante Pieramici, MD, codirector of the California Retina Research Foundation and assistant clinical professor of ophthalmology at the Doheny Eye Center in Southern California, presented the results of the Phase 2 LUNA trial of ixoberogene Soroparvovec (Ixo-vec) intravitreal gene therapy for the treatment of 

neovascular age-related macular degeneration (AMD).

The trial aimed to validate the efficacy and safety of a single injection ixo-vec in extending dosage intervals. Participants were randomized across two Ixo-vec doses, one of 6E10 and one of 2E11 vg/eye, which were given along with multiple corticosteroid prophylactic regimens including oral prednisone +/- topical difluprednate +/- IVT dexamethasone.

“I think this is a big potential advantage,” Pieramici told 

. Currently we use intravitreal injections, and even despite the newer anti-VEGF agents, patients generally need to have injections every 4-8, 12-16 weeks. It’s relatively frequent intravitreal injections and if they miss an injection, life gets in the way, they get hospitalized or something, then they get vision loss, and it may not come back. I think Ixo-vec potentially offers, at least for most patients…a potential one shot therapy.”

The study’s primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Secondary endpoints included the proportion of patients remaining aflibercept injection free, number of supplemental aflibercept injections overall, and mean change in central subfield thickness (CST).

A total of 60 patients were enrolled with a mean age (standard deviation [SD]) of 76.6 +/- 7.8 years and a time since diagnosis of 3.0 +/- 2.9 years. These patients received 10.1 +/- 2.6 annualized anti-VEGF injections over the year leading up to receiving Ixo-vec. Baseline mean BCVA and CST were 72.3 (7.7) ETDRS letters and 350.6 (115.2) µm, respectively.

By week 52, investigators noted maintenance of BCVA and CST with a least squares mean change of -2.1 (6E10) and -1.8 (2E11) ETDRS letters and -10.2µm (6E10) and -21.9µm (2E11), respectively. 54% of 6E10 recipients and 69% of 2E11 recipients received no aflibercept injections. 75% (6E10) and 79% (2E11) needed ≤1 supplemental aflibercept injection, while 89% (6E10) and 90% (2E11) needed ≤2 supplemental injections.

After treatment, patients were surveyed about treatment preference. In total, 93% of patients preferred Ixo-vec over previous anti-VEGF therapy. Additionally, there were no serious treatment-related adverse events during the study. All adverse events related to Ixo-vec were mild or moderate.

Pieramici and colleagues indicated that the results of LUNA highlighted the safety, efficacy, and tolerability of Ixo-vec in maintaining visual and anatomic endpoints over 52 weeks, with more than 50% of patients requiring no additional therapy.

“I think it’s a very exciting time in gene therapy,” Pieramici said. “This is using it not to treat an inherited retinal disease, but using gene therapy as a biofactory approach as opposed to intravitreal injections. This, we’re hoping, is going to significantly reduce the treatment burden.”

Dante Pieramici, MD reports the following disclosures: Adverum, Eyepoint, Genentech, Inc., NGM Bio, Neurotech, Opthea, Perceive, Regeneron, Regenxbio, SMIR, Stealth, Unity: Code S (non-remunerative): None; Adverum, Gemini, Genentech, Inc., Iveric Bio, NGM Bio, Regeneron, Regenxbio: Code C (Consultant/Contractor): None; 4DMT, Adverum, Apellis, Chengdu Kanghong, Clearside, Eyepoint, F. Hoffmann-La Roche Ltd., Genentech, Inc., Iveric Bio, Jenssen, Kodiak Sciences, Novartis, Ocular Therapeutix, Ocurion, Opthea, Regeneron, Regenxbio, Resolute, Unity, Valo: Code F (Financial Support): None; Gemini: Code I (Personal Financial Interest): None

Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Phase 2 LUNA 52-Week Data

. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 – May 8, 2025.

Videos

Ixo-vec, a potential one shot therapy for age-related macular degeneration has achieved noninferior results in maintaining best-corrected visual acuity and central subfield thickness.

Aquatic exercise for the short term, and then resistance training for the long term, were the most effective therapeutic exercises (TE) for reducing pain intensity in women with fibromyalgia, according to a new network meta-analysis (NMA).

“To date, we have not found any publications that compares all TE approaches with each other for the treatment of pain in fibromyalgia. Because the disease affects mainly women and the response to treatment is influenced by a multitude of factors, including gender, the objective of this study was to analyze the efficacy of different TE approaches in pain intensity in women with fibromyalgia and to identify which exercise approach is the most effective through an NMA of randomized clinical trials (RCTs),” lead investigator Álvaro-José Rodríguez-Domínguez, Department of Health and Sports, Pablo de Olavide University, Seville, Spain, and colleagues wrote.

Rodríguez-Domínguez and colleagues performed an NMA of RCTs evaluating the effects of TE on pain intensity for women with fibromyalgia from 6 databases. They assessed methodological quality using the Physiotherapy Evidence Database scale and determined the size of the effect and the clinically important difference in both the short-term (≤3 months) and long-term (>3 months).

The investigators identified 61 studies and included 51in the quantitative synthesis (n = 2873). Finally, 15 TE interventions and 8 comparison interventions (comparators) were identified. They found that aquatic exercise (p-score, 0.8713) provided the best benefits in the short-term and resistance training provided the best benefits in the long-term (p-score, 0.9749). They also found statistically significant differences in favor of aquatic exercise, Pilates, qigong, resistance training, virtual reality, mixed exercise, and aerobic exercise in the short-term; and in favor of resistance training, dance, functional training, aquatic exercise, virtual reality, and aerobic exercise in the long-term compared to usual care.

“Our findings have significant clinical implications for several reasons. Most importantly, [they] can serve as a valuable guide for selecting the most appropriate TE approaches to reduce pain intensity in women with fibromyalgia. This decision should also be made based on the patient's characteristics and preferences, as this is a key factor in improving adherence to treatment. These findings could also contribute to a change in the current paradigm regarding TE prescription in fibromyalgia, because the "gold standard" recommendation of aerobic exercise should be replaced by other more effective approaches,” Rodríguez-Domínguez and colleagues concluded.

Other recent research focused on benefits of exercise in people with fibromyalgia found that aquatic exercise and other forms of exercise 

. Specifically, investigators found that land-based aerobic exercise training in combination with flexibility training showed a standardized mean difference (SMD) of −4.69 (95% CI, -8.14 to -1.28) and aquatic-based aerobic exercise training showed a SMD of-2.63 (95% CI, -4.74 to -0.58) compared to placebo or sham. The investigators also found some suggesting that electrotherapy, weight loss, dental splints, antipsychotics, tricyclics, land-based strengthening exercise, and psychological and behavioral therapy with a focus on sleep, may moderately affect sleep.

Rodríguez-Domínguez ÁJ, Rebollo-Salas M, Chillón-Martínez R, Rosales-Tristancho A, Villa-Del-Pino I, Jiménez-Rejano JJ. The most effective therapeutic exercises for pain intensity in women with fibromyalgia: A systematic review and network meta-analysis. 

Published online May 3, 2025. doi:10.1016/j.bjpt.2025.101226

Hudson J, Imamura M, Robertson C, et al. Effects of Pharmacologic and Nonpharmacologic Interventions for the Management of Sleep Problems in People With Fibromyalgia: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. 

Pubished online February 10, 2025. Accessed April 25, 2025. doi: 10.1002/acr.25505

A recent network meta-analysis identified aquatic exercise as the most effective short-term therapeutic exercise for reducing pain intensity in women with fibromyalgia, while resistance training was most effective in the long term. The study analyzed various therapeutic exercise approaches through randomized clinical trials, highlighting significant differences favoring aquatic exercise, Pilates, qigong, and others over usual care. These findings suggest a shift from the traditional aerobic exercise recommendation to more effective alternatives. Additionally, other research indicates that exercise, including aquatic and land-based aerobic training, can improve sleep problems in fibromyalgia patients.

A new meta-analysis reveals aquatic exercise and resistance training as the top therapeutic exercises for reducing fibromyalgia pain in women.

Aquatic Exercise, Resistance Training Most Beneficial for Reducing Fibromyalgia Pain

Evolocumab may help reshape high-risk plaque in the 

, with the drug reducing microcalcification activity and shifting plaque toward a lower-risk profile over 18 months in patients with extensive noncalcified plaque at baseline in a new study.

Evolocumab, a human monoclonal antibody targeting PCSK9, was first approved by the US Food and Drug Administration (FDA) in August 2015 to lower low-density lipoprotein cholesterol (LDL-C) in patients needing additional reduction. In December 2017, it became the first PCSK9 inhibitor approved to prevent heart attack, stroke, and coronary revascularization in adults with established CVD.

“This discovery has important implications for understanding how evolocumab improves cardiovascular outcomes,” said Daniel S. Berman, MD, director of cardiac imaging in the department of cardiology in the Smidt Heart Institute at Cedars-Sinai and principal investigator of the study.

Berman and colleagues highlighted the lack of evidence on the impact of evolocumab on underlying coronary disease activity by positron emission tomography (PET) and coronary tree plaque composition by coronary computed tomography angiography (CTA). For this imaging study, the team measured the change in coronary plaque composition on coronary CTA and coronary microcalcification on F-sodium fluoride (NaF) PET after evolocumab.

A single-arm, prospective, open-label study, investigators enrolled patients with >440 µL overall coronary artery or >250 µL in any single plaque, who underwent baseline and 18-month follow-up coronary CTA and F-NaF PET. The team determined disease activity by maximum target-to-background ratios at the lesion level and by coronary microcalcification activity for the entire coronary tree.

Overall, 47 patients, with a mean age of 61.8 years and 87% male, with 196 lesions, were included in the study. Among this population, 23 (48.9%) were asymptomatic, 16 (34%) presented with chest pain, and 8 (17%) presented with dyspnea, while 4 (8.5%) had a prior coronary artery disease history.

Across a mean of 18 months, Berman and colleagues identified no notable change in total plaque volume (716.2 ± 431.4 µL to 710.8 ± 456.2 µL; difference, 5.4 ± 97.4 µL; 

 = 0.705). The investigative team identified changes in plaque composition, including a significant reduction in noncalcified plaque (607.3 ± 346.8 µL to 562.1 ± 337.3 µL, difference: 45.2 ± 63.8 µL;

 < 0.001) and low-attenuation noncalcified plaque (37.1 ± 28.9 µL to 20.4 ± 15.4 µL, difference: 16.6 ± 23.5 µL; 

On the other hand, the analysis identified an increase in calcified plaque over 18 months (108.9 ± 133.7 µL to 148.7 ± 175.3 µL, difference: 39.8 ± 56.1 µL; 

 < 0.001). Further analysis revealed a significant reduction in coronary microcalcification activity (1.35 ± 1.68 to 1.08 ± 1.37; 

 = 0.004) and lesion target-to-background ratio (1.73 ± 0.85 to 1.62 ± 0.83;

“Most attention has been placed on the cholesterol-lowering effect of PCSK9 inhibitors,” said Donghee Han, MD, an internal medicine resident at Cedars-Sinai Medical Center and co-first author of the study. “Our findings demonstrate that reducing inflammation may be an important mechanism for reducing the risk of heart attack with these powerful drugs.”

Han D, Tzolos E, Park R, et al. Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography. JACC Cardiovasc Imaging. 2025;18(5):589-599. doi:10.1016/j.jcmg.2025.01.005

FDA approves Amgen’s new cholesterol-lowering medication RepathaTM (evolocumab). Amgen. August 27, 2025. Accessed May 8, 2025. 

https://www.amgen.com/newsroom/press-releases/2015/08/fda-approves-amgens-new-cholesterollowering-medication-repatha-evolocumab

FDA approves Amgen’s Repatha® (evolocumab) to prevent heart attack and stroke. Amgen. December 1, 2025. Accessed May 8, 2025. 

https://www.amgen.com/newsroom/press-releases/2017/12/fda-approves-amgens-repatha-evolocumab-to-prevent-heart-attack-and-stroke

Cedars-Sinai. Research: How cholesterol drug may prevent heart attacks. Newswise. May 5, 2025. Accessed May 8, 2025. 

https://www.newswise.com/articles/research-how-cholesterol-drug-may-prevent-heart-attacks

Evolocumab, a PCSK9 inhibitor, has shown potential in reshaping high-risk arterial plaque by reducing microcalcification activity and shifting plaque composition towards a lower-risk profile over 18 months. Initially approved to lower LDL-C, evolocumab is now recognized for its role in preventing cardiovascular events. A study involving 47 patients demonstrated significant reductions in noncalcified and low-attenuation noncalcified plaque, alongside increased calcified plaque. These findings suggest that evolocumab's benefits extend beyond cholesterol reduction, potentially reducing heart attack risk through inflammation reduction.

Evolocumab reshapes arterial plaque, reducing cardiovascular risk by lowering microcalcification and shifting plaque composition over 18 months.

Evolocumab May Shift Plaque Profile Toward Lower Cardiovascular Risk

Significant psychosocial and occupational burdens are reported by caregivers of adolescents living with 

, recent findings suggest, as well as mental and emotional well-being impairments.

These data resulted from an analysis by such investigators as Rodney Sinclair, from Sinclair Dermatology in Australia, who noted the value of assessing the effects of alopecia areata on caregiver quality of life for recognizing any unmet needs among such individuals. They also noted determination of caregivers’ needs in terms of healthcare and social support is invaluable.

Prior to their current analysis, the investigative team highlighted that there had been a notable lack of research evaluating the psychosocial and occupational effects of the hair loss condition on parents and caregivers.

“This study aimed to investigate the impact of [alopecia areata] on psychosocial well-being, work productivity and [quality of life] among caregivers of adolescents with [alopecia areata] living in Australia,” Sinclair and colleagues wrote.

The investigative team conducted a non-interventional, cross-sectional online survey in Australia from April - July 2023, working to evaluate the experiences of caregivers of adolescents living with alopecia areata. They assessed both dyadic caregivers—those whose adolescent dependents also filled out the study's survey—and non-dyadic caregivers—whose dependents did not fill out the survey or were unable to take part.

Recruitment of subjects was supported by the Australia Alopecia Areata Foundation (AAAF), which helped disseminate the survey nationally. Those deemed eligible as respondents were parents or legal guardians in the age range of 18 or older. They would also be required to be currently caring for adolescents aged 12 - 17 years who were living with a medically confirmed, self-reported diagnosis of alopecia areata for a minimum of 3 months before the survey's completion.

Caregivers involved in the study as subjects filled out a set of online screening questions to confirm their eligibility. The questionnaire provided to participants was completed online and involved the answering of inquiries related to treatment and clinical details (gathered from caregivers for nondyadic participants and from adolescents themselves in dyadic pairs), sociodemographic data, and information on the psychosocial and work-related impacts of caring for an adolescent with alopecia areata.

Overall, Sinclair and colleagues found alopecia areata among adolescents has notable psychological effects on their guardians and caregivers. Despite only 24.5% of all caregivers noting symptoms of depression—a finding the investigators noted was consistent with a prior US analysis reporting rates ranging from 7.3% - 18.3%—the prevalence of anxiety was shown by the team to be significantly higher in this sample at 62.3%.

This was compared with the US study's range of 20.7% - 42.7%. Notably, the investigative team highlighted that the severity observed among dyadic caregivers of adolescents' hair loss showed limited impact on reported levels of anxiety or depression.

Quality of life was evaluated by the team via the Quality of Life in Child’s Chronic Disease Questionnaire (QLCCDQ), with guardians and caregivers in the analysis highlighting lower scores across all domains compared to a reference population of caregivers of children labeled as healthy. Reported mean scores included: symptoms (4.0), emotions (4.0), family (5.8), social (5.2), and occupational (5.3), compared scores of 5.9, 6.2, 6.3, 6.6, and 6.4, respectively, among those in the healthy cohort. Such findings suggest a reduced quality of life linked with caregiving for adolescents with the hair loss condition.

Sinclair and coauthors pointed to a few notable differences between dyadic and nondyadic caregivers in their study's results. Nondyadic caregivers were found to have higher anxiety and depression levels as well as lower QLCCDQ scores compared to their dyadic counterparts. This finding would suggest a heavier psychosocial and occupational burden.

Although the investigators noted that the reason for such disparities is not definitively clear, 1 possible explanation they highlighted was that adolescents dealing with more severe alopecia areata effects may have opted out of taking part in the survey. This decision would, thereby, raise stress levels among their caregivers.

Additionally, the investigative team noted that over half of caregivers (50.9%) had experienced impairments in their daily activities. They also noted that nearly half (49.1%) of subjects pointed to impacts in their work performance, further underscoring the notable occupational burden of caring for an adolescent with alopecia areata.

“The study revealed a substantial psychosocial and occupational burden and impaired emotional well-being among caregivers of adolescents with [alopecia areata],” they concluded.

 “[Alopecia areata] in adolescents can profoundly affect the entire family, and these findings highlight the importance of recognising and understanding the disease-related burden that extends beyond the individual patient.”

Sinclair R, Eisman S, Lee CMY, da Fonseca Pereira C, et al (2025). Psychosocial and Occupational Burden on Caregivers of Adolescents With Alopecia Areata in Australia. Australas J Dermatol. 

E Putterman, DP Patel, G Andrade, et al. “Severity of Disease and Quality of Life in Parents of Children With Alopecia Areata, Totalis, and Universalis: A Prospective, Cross-Sectional Study,” Journal of the American Academy of Dermatology 80, no. 5 (2019): 1389–1394, https://doi.org/10.1016/j.jaad.2018.12.051.

Recent findings highlight the significant psychosocial and occupational burdens faced by caregivers of adolescents with alopecia areata, including mental and emotional well-being impairments. A study conducted in Australia assessed the impact of alopecia areata on caregivers' quality of life, revealing high anxiety levels and reduced quality of life scores compared to caregivers of healthy children. The study also found that nondyadic caregivers experienced higher anxiety and depression levels. These findings underscore the importance of recognizing the broader disease-related burden on families beyond the individual patient.

Notable psychosocial and occupational burdens, as well as impairments to emotional well-being, were seen among caregivers of adolescents with alopecia.

Study Highlights Psychosocial Burden on Caregivers of Adolescents with Alopecia Areata

A new study identified factors that increased the odds of 

 among older adults at emergency department visits, such as medications and intravenous (IV) contrast.

Limited research focuses on anaphylaxis characteristics and outcomes in older adults. According to the KeepSmilin4Abbie Foundation, older adults may not experience the typical anaphylaxis symptoms of skin rash, difficulty breathing, and nausea. Rather, they may experience chest pain, confusion, and fainting.

 A heart attack or a stroke can mask these symptoms, delaying the treatment of the life-threatening anaphylaxis.

identified several trends among adults with anaphylaxis,

 including increasing age linked to more severe presentations.

 The study examined participants (mean age: 31 years) who visited St. Vincent’s Hospital in Sydney, Australia, with anaphylactic presentations from January 2009 to December 2018. Investigators discovered individuals over 65 years were more likely to have identifiable triggers for anaphylaxis than younger individuals (< 65 years), with medications being the most prominent trigger in this age group (75% vs 20.1%).

Another study also showed that medication was the most frequent anaphylaxis trigger in older adults (

= .039), which was more common than in younger adults.4 Cardiovascular symptoms were seen more in older adults experiencing anaphylaxis than in younger adults. Hospital rates and adrenaline administration were also more frequent in older adults than younger adults (

Food was a common trigger in older adults, but more common among younger adults, and respiratory symptoms were significantly less common in older adults. Skin was the most affected organ in older and younger adults but was less affected in older adults.

Investigators, led by Marie-Joy Nduwimana, from the department of emergency medicine at Mayo Clinic, conducted a cohort study to expand on this previous research and learn more about how the presentation of anaphylaxis differed in older adults (≥ 65 years) compared with younger adults (aged 18 – 64 years).1 They compared triggers, presentation, management, and outcomes of anaphylaxis emergency department visits in older and younger adults. The team analyzed data from both the pre-hospital setting and the emergency department.

The study included adults who met the anaphylaxis criteria from April 2008 to December 2022. Among 1422 visits, 212 (14.9%) were for older adults. The team analyzed visit characteristics and outcomes by age group using chi-squared analysis and multivariable logistic regression.

Compared with younger adults, anaphylaxis among older adults was more likely to be triggered by medications (34.0% vs 21.3%; odds ratio [OR] 1.85; 95% confidence interval [CI], 1.34 – 2.55) and IV contrast (13.2% vs 5.6%; OR 2.50; 95% CI, 1.55 – 4.04). Older adults also had increased odds of severe anaphylaxis (adjusted OR [aOR], 1.57; 95% CI, 1.12 – 2.21), requiring endotracheal intubation (aOR, 6.24; 95% CI, 2.69 – 14.48) and hospital or intensive care unit (ICU) admission (aOR, 1.78; 95% CI, 1.19 – 2.67).

The study also showed older adults were more likely to arrive via emergency medical services (EMS) (56.1% vs 34.0%; OR, 2.56; 95% CI, 1.89 – 3.46) but less likely to receive EMS-administered epinephrine (26.0% vs 32.4%; aOR, 0.46; 95% CI, 0.27 – 0.77).

“Visits among older adults had increased odds of anaphylaxis from medications and IV contrast, cardiovascular symptoms, and more severe outcomes, including intubation and ICU admission,” investigators concluded. “Improved EMS epinephrine administration and prehospital guidelines could enhance outcomes for older adults with anaphylaxis.”

Nduwimana MJ, Liu SW, Goldberg EM, Bellolio F, Mullan AF, Wilson R, Campbell RL. Characteristics and Outcomes of Anaphylaxis in Emergency Department Visits Among Older Adults. J Allergy Clin Immunol Pract. 2025 Apr 22:S2213-2198(25)00380-0. 

Smith, T. Increasing Age Linked to More Severe Anaphylaxis, Medications Frequent Trigger for Older Adults. HCPLive. July 25, 2023. 

https://www.hcplive.com/view/increasing-age-linked-more-severe-anaphylaxis-medications-frequent-trigger-for-older-adults

Anaphylaxis and Aging: Crucial Facts Everyone Needs To Know. The KeepSmilin4Abbie Foundation. 

https://keepsmilin4abbie.org/anaphylaxis-and-aging-crucial-facts-everyone-needs-to-know/

Yıldız E, Arslan Ş, Çölkesen F, Evcen R, Sadi Aykan F, Kılınç M. Anaphylaxis in older adult patients: a 10-year retrospective experience. World Allergy Organ J. 2022 Jul 14;15(7):100665. doi: 10.1016/j.waojou.2022.100665. PMID: 35891674; PMCID: PMC9293944.

A recent study highlights the increased risk of anaphylaxis in older adults during emergency department visits, with medications and IV contrast as significant triggers. Older adults often present atypical symptoms, complicating diagnosis and treatment. The study found that older adults are more likely to experience severe anaphylaxis, requiring intubation and ICU admission. Despite higher EMS usage, older adults receive less EMS-administered epinephrine. The findings suggest that improved prehospital guidelines and EMS epinephrine administration could enhance outcomes for older adults experiencing anaphylaxis.

New research reveals older adults face higher anaphylaxis risks from medications and IV contrast, often presenting with severe symptoms and outcomes.

Medications, IV Contrasts Increase Anaphylaxis Odds in Older Adults

Sleep Disorders and PBC Disease Severity, with Ana Marenco Flores, MD

New research is shedding light on the prevalence of sleep disorders in patients with 

, additionally highlighting their association with worse biochemical markers, greater symptom burden, and reduced treatment response rates.

The data were presented at Digestive Disease Week (DDW) 2025 by Ana Marenco Flores, MD, a research fellow in medicine in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School, and highlight the potential benefit of assessing sleep disorders as part of routine clinical care and implementing timely interventions for improving outcomes and quality of life in this patient population.

“In clinical practice, almost 80 to 85% of patients are going to tell you they are having fatigue, having trouble sleeping, having a lot of itching, or having difficulties at their job because they’re feeling tired a lot,” Marenco Flores explained to 

. “There’s a really strong association between quality of life or patient reported outcomes with PBC.”

To assess this association in the context of sleep disorders, she and colleagues conducted a prospective study of patients with PBC enrolled in a single-center Autoimmune Liver Registry between 2018-2024. Diagnoses were based on EASL criteria and all patients received standard ursodeoxycholic acid therapy with ≥ 1 year of follow-up. Exclusion criteria included autoimmune overlap, drug-induced liver injury, viral hepatitis, alcohol-associated liver disease, and incomplete questionnaires.

Sleep disorders and fatigue were assessed using the CLDQ and PBC-40 questionnaires, while pruritus was evaluated using the Visual Analogue Scale (VAS) and the 5-D Itch Scale at the 1-year follow-up. Treatment response was defined according to Paris-II criteria.

Among 104 patients with PBC, 33% reported sleep disorders. Investigators noted this group had significantly increased alkaline phosphatase (ALP) levels (median 203 IU/L vs 122 IU/L; 

= .003) and total bilirubin (TBIL) levels (median 0.6 mg/dL vs 0.4 mg/dL; 

= .031) compared to those without sleep disorders. They also reported more severe fatigue (

<.001), and a significantly lower likelihood of achieving treatment response (44% vs 94%; 

<.001). Of note, pruritus severity did not differ significantly between the groups (

“Before, there were studies that said that most patients have difficulty sleeping because they have itch. In our cohort, we saw that even though some patients have itching and sleep issues, a lot of them didn't report itching but still had sleep difficulties,” Marenco Flores said.

Multivariable analysis identified greater ALP (odds ratio [OR], 1.01; 

<.001) and poorer self-rated health (OR, 3.4; 

<.001) as independent predictors of sleep disorders.

“I think for us as a lab, especially in autoimmune liver diseases, we aim to also assess patient reported outcomes,” Marenco Flores said. “The objective parameters are obviously really important, but sometimes patients will do great with the labs and the treatment and still have some complaints. For them, feeling good in every aspect of their life is as good as having a great ALP or another imaging test, so that's what we aim for.”

Editors’ note: Marenco Flores has no relevant disclosures.

Marenco-Flores A, Amaris NR, Barba R, et al. SLEEP DISORDERS IN PRIMARY BILIARY CHOLANGITIS: INDEPENDENT OF PRURITUS BUT PREDICTIVE OF DISEASE SEVERITY IN A U.S. SINGLE-CENTER COHORT. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

Findings suggest sleep disorders are common in PBC and are linked to worse biochemical markers, greater symptom burden, and reduced treatment response rates.

A recent study has indicated a causal relationship between environmental factors and both 

IgAN is the most prevalent glomerulonephritis globally, carrying a considerable lifetime risk of kidney failure. Previous research has indicated a “four-hit” progression pattern for IgAN, although more recent studies have noted its failure to address the disease's geographic distribution, racial diversity, and clinical heterogeneity.

MN is an autoimmune disease triggered by autoantibodies attacking podocyte antigens, which leads to the in situ production of immune complexes. However, little is known about the pathogenesis or etiology. 40-60% of patients with nephrotic syndrome progress to end-stage renal disease or die from cardiovascular or thrombotic events.

“Previous [Mendelian randomization (MR)] analyses have revealed that external environmental factors can influence disease progression by changing an individual’s internal environmental factors (e.g., personal behavior and metabolism),” wrote Chunmin Li, department of nephrology, Tongren Hospital of Wuhan University, and colleagues. “We performed a two-step MR analysis to dissect the mediating role of individual behavior, metabolism in the association of the external environment with disease, offering novel insights into their prevention.”

Recent research has identified a causal link between environmental factors and the development of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN). The study utilized Mendelian randomization to explore how external environmental factors influence disease progression through individual behavior and metabolism. Data from genome-wide association studies (GWAS) were analyzed, revealing novel relationships between IgAN and factors like cheese intake and cognitive performance, and between MN and beef intake. The findings suggest potential strategies for preventing and managing these nephropathies, though further research is needed.

Recent research uncovers how lifestyle and environmental factors influence the incidence of IgAN and membranous nephropathy.

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