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

Advancing Research and Care in Juvenile Arthritis, With Yukiko Kimura, MD

Management for juvenile idiopathic arthritis (JIA), the most common rheumatologic disease in children, has undergone a dramatic shift in outcomes over the past 2 decades. Once a condition that frequently left children with visible disability, limited mobility, and lifelong complications, JIA is now often managed successfully with targeted therapies that prevent severe damage and help children live active, healthy lives. This progress is largely attributed to the advent of biologics, beginning with TNF inhibitors and now extending to a wide array of therapies with distinct mechanisms of action, including IL-6 inhibitors, T-cell co-stimulation blockers, and JAK inhibitors.

 The expansion of treatment options has not only improved quality of life but has also transformed how clinicians approach disease control in pediatric populations.

Alongside therapeutic breakthroughs, international collaboration has become a driving force in JIA research. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) in North America and the Pediatric Rheumatology European Society (PReS) have joined efforts to launch some of the first global investigator-initiated studies in this space. One such initiative, the SMART-JIA trial, seeks to address a longstanding clinical question: how to optimize treatment strategies for patients who do not respond to first-line biologics.

 With multiple biologic and targeted options available, determining which pathway to pursue after treatment failure remains a challenge for clinicians. Another critical area of investigation focuses on when and how it may be safe to taper or discontinue therapy, an issue of great importance for patients and families navigating long-term treatment.

 spoke with Yukiko Kimura, MD, Chief of Pediatric Rheumatology at Hackensack University Medical Center, and Professor of Pediatrics at the Hackensack Meridian School of Medicine, to learn more about her experience with the evolving treatment landscape. Kimura, who is also cochair of the CARRA Registry and Research Oversight Committee (RROC), also highlighted the importance of ongoing research to address these pressing questions in JIA care.

“The kids that get diagnosed [with pediatric arthritis] can really benefit from knowledge of specialists in this area who know how to use [biologics] and can treat them the way that they should be,” Kimura said.

Shishov M, Weiss PF, Levy DM, et al. 25 Years of Biologics for the Treatment of Pediatric Rheumatic Disease: Advances in Prognosis and Ongoing Challenges. 

. 2025;77(5):573-583. doi:10.1002/acr.25482

Trial of Sequential Medications After TNF Failure (SMART) and Precision Treatment Decisions in Juvenile Idiopathic Arthritis. CARRA. 

https://carragroup.org/grant/trial-of-sequential-medications-after-tnf-failure-smart-and-precision-treatment-decisions-in-juvenile-idiopathic-arthritis/

Videos

Kimura highlighted some of her ongoing research tackling high priority questions in JIA.

A recent study suggests that confounding may explain the increased risks of 

associated with prenatal prescribed opioid analgesic (POA) exposure.

Many obstetrician-gynecologists prescribe opioid analgesics to help manage their patients’ pregnancy pain. However, research has suggested a potential link between prenatal POA exposure and neurodevelopmental disorders.

It was not known if the association between prenatal POA exposure and neurodevelopmental disorders in children is causal or driven by confounding. In this retrospective study, investigators analyzed how the dose and duration of POA use during pregnancy were associated with autism and ADHD risk in children.

“We wanted to conduct this study to help provide more information for pregnant individuals and their physicians who are trying to make complex decisions about how to best manage pain during pregnancy,” said lead investigator Emma N. Clearly, BA, from Indiana University Bloomington, and colleagues, in a statement.

 “While this study is not able to rule out small increased risks with high amounts of exposure, the results suggest that there is not a causal effect of prescribed opioid analgesics on risk for two common neurodevelopmental disorders, providing more data to support decision-making.”

Using national register data from Sweden, this study examined a population-based cohort, with nearly half female (48.6%).

 The ASD cohort included 1,267,978 children born between July 1, 2007, and December 31, 2018, with a follow-up through 2021. Since ADHD is typically diagnosed later, investigators applied a shorter eligibility window, including 918,771 children born through December 31, 2015.

The team used test-mining algorithms to calculate cumulative dose and duration of POA exposure during pregnancy from filled prescriptions and to identify those prescribed on an “as needed” basis.

 Outcomes included inpatient or outpatient clinical diagnoses of ASD and ADHD or dispensed ADHD medications.

To address unmeasured confounding, the analysis incorporated several comparison groups: children whose birthing parent had a diagnosed painful condition but did not receive POAs, children whose birthing parent received POAs in the year prior to but not during pregnancy, and unexposed siblings.

Among the 1,267,978 children, 4.4% were exposed to POAs when in their mother’s womb. At 10 years old, the cumulative incidence of ASD was 3.6% and 2.9% among children exposed to high and low POA doses, respectively, compared with 2% among children unexposed to POAs.

Unadjusted models (hazard ratio [HR], 1.74;

1.63–1.87) and models adjusted for measured covariates (HR, 1.34

 95% CI, 1.24–1.44) showed that the cumulative maximum POA dose was associated with an increased risk of ASD. However, these associations were weak or nonexistent in alternative study designs, particularly when compared with children whose birthing parent had received POAs before, but not during, pregnancy (HR, 1.10; 95% CI, 1.00 – 1.21). The sibling comparison analysis showed no associations between ASD and POA exposure (HR, 0.99; 95% CI, 0.81 – 1.21).

Investigators noted that they did not assess the impact of extremely high doses and long durations of opioids due to limited data in the Swedish cohort.

“We are excited to share our findings because we believe that they have important clinical implications,” said investigator Ayesha C. Sujan, PhD, from Stanford University School of Medicine, in the statement.

 “Our findings suggest that the observed associations between prenatal exposure to opioid analgesics and two major neurodevelopmental disorders—autism and ADHD—are largely driven by factors leading up to opioid analgesic use rather than the opioid exposure itself. Our results, therefore, elucidate the critical need to provide pregnant individuals experiencing pain with psychosocial support and evidence-based pain management tools. These can include both pharmaceutical and non-pharmaceutical approaches.”

Cleary EN, Sujan AC, Rickert ME, et al. Prescribed opioid analgesic use in pregnancy and risk of neurodevelopmental disorders in children: A retrospective study in Sweden. 

. 2025;22(9):e1004721. Published 2025 Sep 16. doi:10.1371/journal.pmed.1004721

Prescribed opioid pain medications during pregnancy likely aren’t associated with increased risk of autism, ADHD. EurekAlert! Published September 16, 2025. Accessed September 17, 2025. https://www.eurekalert.org/news-releases/1097557

Articles

A recent study explored the potential link between prenatal prescribed opioid analgesic (POA) exposure and neurodevelopmental disorders such as autism spectrum disorder (ASD) and ADHD. The research, using Swedish national register data, analyzed the dose and duration of POA exposure during pregnancy. Findings suggest that the observed associations are likely due to confounding factors rather than a causal relationship. The study emphasizes the importance of providing pregnant individuals with psychosocial support and evidence-based pain management strategies, both pharmaceutical and non-pharmaceutical, to manage pregnancy-related pain effectively.

A study suggests associations between opioids during pregnancy and neurodevelopmental disorders are mainly due to confounding factors, not causal effects.


Prenatal Opioid Pain Medications Likely Not Linked to Autism or ADHD Risk

Dexpramipexole significantly improved lung function compared to placebo as an add-on oral therapy in people with eosinophilic 

, according to the latest findings from the phase 3 EXHALE-4 study announced by Areteia Therapeutics.

“More than half of people with asthma have the eosinophilic subtype, yet there remains a profound need for easily administered oral treatment options that can help address their symptoms, which are often severe,” Ian Pavord, MA, DM, Professor of Respiratory Medicine at the University of Oxford, United Kingdom, and member of Areteia’s Scientific Advisory Board, said in a statement.

 “Initial results from the Phase III EXHALE-4 study are extremely promising, particularly the statistically significant improvement in lung function and the reduction in eosinophils observed with dexpramipexole versus placebo, which show the potential for dexpramipexole to become the first oral treatment approved for eosinophilic asthma.”

EXHALE-4 is a randomized, double-blind, placebo-controlled Phase 3 study evaluating dexpramipexole, an investigational oral small molecule. It is formulated as dexpramipexole dihydrochloride and 75 mg and 150 mg dexpramipexole dihydrochloride are equivalent to 56 mg and 112 mg dexpramipexole, respectively (doses mentioned refer to dexpramipexole dihydrochloride).

The therapy is proposed to inhibit the maturation of eosinophils in the bone marrow, based on evidence from cell cultures and human biopsies, thereby lowering peripheral blood and tissue eosinophil levels.

The study is evaluating dexpramipexole in 600 participants aged ≥12 years with inadequately controlled moderate-to-severe asthma and blood Absolute Eosinophil Count ≥300 cells/μL. They continued their usual asthma medications and were randomized to add either dexpramipexole (150 mg or 75 mg) or placebo in a 5:5:1 ratio, respectively. Participants were randomly assigned to placebo BID, 150 mg BID, or 75 mg BID dexpramipexole groups in a 5:5:1 ratio respectively.

The study is primarily evaluating the absolute change from baseline in pre-bronchodilator forced expiratory volume (pre-BD FEV

) averaged over Weeks 20 and 24 between 150 mg twice daily (BID) dexpramipexole dose and placebo. Dexpramipexole 75mg BID was included to assess eosinophil lowering effects in blood and pharmacokinetic/pharmacodynamic relationship.

Investigators found that dexpramipexole significantly improved lung function and met the study’s primary endpoint, with a statistically significant improvement in pre-BD FEV

in the dexpramipexole 150 mg BID group compared with placebo. Significant improvements in lung function were observed as early as Week 4. Dexpramipexole 150 mg BID and 75mg BID also significantly reduced blood AEC averaged over Weeks 20 and 24 compared with placebo. The therapy was well tolerated, with a safety profile similar to previous studies. More detailed data will be presented at an upcoming medical meeting.

“We are pleased to report positive topline results for the EXHALE-4 Phase III study, which demonstrate dexpramipexole’s ability to address the unmet needs of people with eosinophilic asthma by improving their lung function. Dexpramipexole has the potential to be the first oral treatment for this indication,” Jorge Bartolome, President and Chief Executive Officer of Areteia, added.

 “We look forward to presenting the full EXHALE-4 results at an upcoming medical meeting as we also advance the EXHALE-2 and EXHALE-3 studies and work to transform the patient journey in eosinophilic asthma.”

Dexpramipexole previously demonstrated in a significant, dose-dependent reduction in blood AEC at all doses tested (37.5 mg, 75 mg, or 150 mg BID) compared with placebo in a Phase II study in participants with moderate-to-severe eosinophilic asthma with dose-dependent improvements in lung function and a well-tolerated safety profile in other EXHALE studies.

Areteia Therapeutics Announces Positive Topline Results from the First Phase III Study of Oral Dexpramipexole in Eosinophilic Asthma. News release. September 16, 2025. News release. Areteia Therapeutics. 

https://www.businesswire.com/news/home/20250916566261/en/Areteia-Therapeutics-Announces-Positive-Topline-Results-from-the-First-Phase-III-Study-of-Oral-Dexpramipexole-in-Eosinophilic-Asthma

Siddiqui S, Wenzel SE, Bozik ME, et al. Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial. 

. 2023;152(5):1121-1130.e10. doi:10.1016/j.jaci.2023.05.014

Dexpramipexole, an investigational oral therapy, has shown significant improvement in lung function for patients with eosinophilic asthma in the Phase 3 EXHALE-4 study. The study demonstrated a statistically significant increase in pre-bronchodilator forced expiratory volume (pre-BD FEV1) and a reduction in blood eosinophil levels compared to placebo. The therapy was well tolerated, with a safety profile consistent with previous studies. These findings suggest dexpramipexole's potential as the first oral treatment for eosinophilic asthma, addressing a significant unmet need in this patient population.

The EXHALE-4 study evaluating the oral small molecule has met its primary endpoint of improving pre-BD FEV1.

Dexpramipexole Oral Add-On for Asthma Significantly Improves Lung Function Over Placebo

Chelsea R. Perfect, MD, MPH I Credit: Duke University School of Medicine

A study showed that falls were common among participants with systemic lupus erythematosus (SLE), regardless of age.

“Multiple intrinsic factors appear to be contributing to these falls, including loss of balance, weakness, joint instability, and pain…” wrote study investigator Chelsea R. Perfect, MD, MPH, from Duke University School of Medicine, and colleagues.

 “Extrinsic factors likely contributed to the high prevalence of falls, with nearly two-thirds of study participants reporting that they tripped or slipped during their fall.”

SLE is believed to accelerate the aging process due to stress, hormone alterations, and inflammation. The accelerated aging can put patients at risk of geriatric syndromes, including falls.

In the Approaches to Positive, Patient-centered Experiences of Aging with Lupus (APPEAL) study, investigators assessed the burden of and risk factors for falls among patients with SLE regardless of age.

 They also examined what intrinsic and extrinsic factors contributed to the falls.

The team recruited 447 participants aged ≥ 18 years with validated SLE (40.9% aged ≥ 50 years, 91.7% female, and 82.6% Black) from the ongoing population-based Georgians Organized Against Lupus (GOAL) cohort in Atlanta. This sample included participants who had an APPEAL visit between October 8, 2019, and May 12, 2022.

The median disease duration was 14.8 years, with median SLAQ and BILD scores of 11 and 2, respectively. The mean Short Physical Performance Battery score was 9.0, with balance and chair stand sub scores of 3.8 and 1.7, respectively. Most participants had mild limitations in basic and instrumental activities of daily living, with median scores of 6 and 9, respectively.

Investigators also collected self-reported information on falls, including the number of falls and fall-related injuries requiring medical attention over the past year. They also collected self-reported perceived contributing factors.

Nearly a third of patients (30.7%) reported falling in the past year, with 19.2% falling at least twice. Contributing factors for falls included loss of balance (78.1%), slipping or tripping (64.2%), and weakness (53.3%).

Neither age, sex, nor race was associated with falls. Although the study showed that participants aged ≥ 50 years were more likely to report falls than younger participants aged 18 – 34 years, this association was not statistically significant in the multivariable logistic regression analysis adjusted by age, sex, and race (adjusted odds ratio [aOR], 0.82; 95% confidence interval [CI], 0.22 – 3.07). The presence of cognitive impairment was also not associated with a difference in falls.

The study found that greater physical functioning (aOR, 0.50; 95% CI, 0.38–0.66) and performance (aOR, 0.78; 95% CI, 0.71–0.87) were associated with lower odds of falls. Risk factors associated with greater odds of falls included a greater SLE activity (aOR, 1.78; 95% CI, 1.44 – 2.21), greater SLE damage (aOR, 1.22; 95% CI, 1.00 – 1.49), and depressive symptoms (aOR, 1.43; 95% CI, 1.14 to 1.80). Additionally, obesity (aOR, 1.58; 95% CI, 1.04 to 2.41), greater Basic Activities of Daily Living scores (aOR, 1.29; 95% CI, 1.16 to 1.43), and greater Instrumental Activities of Daily Living scores (aOR, 1.14; 95% CI, 1.07 to 1.21) were linked to greater odds of a fall.

Another risk factor was taking medication that increases the risk of falls, such as antidepressants (aOR, 1.82; 95% CI, 1.13 – 2.93), pain medications (aOR, 2.60; 95% CI, 1.68 – 4.00), and opioids (aOR, 4.52; 95% CI, 2.39 – 8.56). Steroids, sedatives, and antihypertensive medications were not associated with increased odds if a fall. Taking ≥ 10 medications, compared with ≥ 5 medications, was associated with a greater risk of falls (aOR, 3.36; 95% CI, 1.83 to 6.16).

Furthermore, being currently employed versus unemployed was associated with a substantially lower odds of reporting falls (aOR, 0.61; 95% CI, 0.40 – 0.94). Additionally, high vs low physical activity was linked to lower odds of falls (OR, 0.33; 95% CI, 0.14 to 0.76).

Sensitivity analyses showed that falls attributed to balance, weakness, or slipping had distinct risk patterns: balance-related falls were more strongly linked to disease activity, depressive symptoms, stress, and medication use; weakness-related falls were influenced by education and race; and slipping-related falls were most strongly tied to employment, physical activity, and depression.

“Future studies could focus on understanding if there are differences between SLE individuals and the general population regarding severity of the falls, incidence of injury, and sequelae of falls,” investigators wrote.

Perfect CR, Bowling CB, Lim SS, et al. Falls Among Individuals With Systemic Lupus Erythematosus: An Observational Study. 

. 2025;7(9):e70098. doi:10.1002/acr2.70098

Byerly LK. Accelerated aging in primary care practice: seeing the downstream effects of social determinants of health

. Presented at: 55th Annual Primary Care Review

Falls are prevalent among systemic lupus erythematosus (SLE) patients, irrespective of age, due to intrinsic factors like balance loss and extrinsic factors such as tripping. The APPEAL study assessed fall risk factors in SLE patients, revealing that greater physical functioning and performance reduce fall risk, while higher SLE activity, damage, depressive symptoms, and obesity increase it. Medication use, particularly antidepressants and opioids, also elevates fall risk. Employment and high physical activity correlate with reduced fall odds. Future research should explore fall severity and injury incidence in SLE versus the general population.

Nearly a third of patients with lupus in APPEAL reported falls, with disease activity, depressive symptoms, and medication use among key risk factors.