How does upadacitinib work in treating SSc-ILD?

Upadacitinib, a JAK inhibitor, works by blocking the activity of Janus kinases (JAKs), which are enzymes involved in inflammation and immune responses.By inhibiting these enzymes, upadacitinib can reduce inflammation and slow the progression of lung damage in SSc-ILD.

what were the main findings of the clinical trial on upadacitinib for SSc-ILD?

The clinical trial demonstrated that patients treated with upadacitinib experienced a reduced rate of decline in forced vital capacity (FVC) compared to those treated with mycophenolate mofetil,a standard treatment for SSc-ILD. This suggests that upadacitinib can effectively slow the progression of lung disease in these patients.

What are the current FDA-approved treatments for systemic sclerosis-associated interstitial lung disease?

Currently, nintedanib and tocilizumab are the only FDA-approved treatments for systemic sclerosis-associated interstitial lung disease (SSc-ILD). upadacitinib is not yet FDA-approved for this specific condition but is approved for other autoimmune diseases.

What are the potential risks associated with using JAK inhibitors like upadacitinib?

Potential risks associated with JAK inhibitors include an increased risk of infections, blood clots, and other adverse effects. Older patients may be more susceptible to these risks, requiring careful monitoring and consideration when prescribing upadacitinib.

Who sponsored the clinical trial on upadacitinib for SSc-ILD?

The clinical trial evaluating upadacitinib for the treatment of systemic sclerosis-associated interstitial lung disease was sponsored by Assiut University.

Pediatric Dermatology Study Links JIA,Age & Immunomodulators to Delayed Onset of Psoriasis in Young TNF-Inhibitor Users

CINCINNATI,OH – A new retrospective study published in Pediatric Dermatology reveals potential predictors for the growth of psoriasis (PD) in children and adolescents undergoing treatment with Tumor Necrosis Factor inhibitors (TNFi) – a common therapy for inflammatory conditions like Crohn’s disease and juvenile idiopathic arthritis (JIA). Researchers at Cincinnati Children’s Hospital Medical Center found that a diagnosis of JIA, older age at the start of TNFi therapy, and concurrent use of immunomodulating drugs are associated with a later onset of PD.

The study, led by Muayad M.Shahin of the University of Cincinnati College of Medicine, analyzed the medical records of 3,418 pediatric patients receiving tnfi therapy between January 2018 and January 2023.The findings offer crucial insights into a known, but often challenging, side effect of these powerful medications.

Understanding TNF-Inhibitors and Psoriasis

TNFi medications – including infliximab and adalimumab – are a cornerstone of treatment for a range of autoimmune and inflammatory diseases affecting children, including Crohn’s disease, JIA, and ulcerative colitis. these drugs work by blocking TNF, a protein that plays a key role in inflammation. However, a paradoxical reaction can occur, where TNFi therapy triggers or exacerbates psoriasis, a chronic skin condition characterized by red, scaly patches.

The Cincinnati children’s study found that 70 patients (2%) developed PD during the study period. The median age at the start of TNFi treatment was 11.7 years, with PD manifesting a median of 16.9 months later. The majority of those affected were female (52.9%) and White (91.4%). Notably, 94% of patients experienced PD at multiple sites on the body.

Key Findings & Treatment Approaches

The research highlighted several important observations:

Resolution Rates: PD rashes resolved in approximately 45.7% of patients, with a median time to resolution of 15.5 months.
Crohn’s Disease Predominance: The majority (71.4%) of patients who developed PD also had Crohn’s disease. Infliximab (52.7%) and adalimumab (44.6%) were the moast commonly used TNFi medications in this group. Treatment Strategies: Treatment for PD primarily involved topical steroids (85.7%), with a notable proportion also receiving systemic medications (15.4%) and non-steroidal topical treatments like tacrolimus, pimecrolimus, and calcipotriene (24.3%).
Treatment Discontinuation: Over half of the patients (57.1%) had their initial TNFi discontinued due to PD. Of those, approximately 30% switched to another TNFi (with a 33% recurrence rate of PD), while 62.5% switched to a different medication class, though PD persisted in 36% of those patients.
Gender & Treatment: Girls were more likely to be prescribed high-potency topical steroids, potentially reflecting differences in disease severity or prescribing patterns.
Predictive Factors: Statistical analysis revealed that a JIA diagnosis was associated with a delayed PD onset (22.6 months later, P = .02). Concomitant immunomodulator use also correlated with later onset (11.0 months later, P = .04), as did starting TNFi therapy at an older age (2.4 months later per year of age, P < .01). Future Research Needed

the authors acknowledge the study’s limitations, including its retrospective design which limited detailed descriptions of the skin eruptions and inconsistencies in defining “severe” PD. They emphasize the need for further research to better understand the factors influencing PD severity in pediatric patients. Specifically,they note the need to clarify whether female sex truly influences severity,as current findings are conflicting.

This research was funded by the National Institute of Arthritis and Musculoskeletal and skin Diseases Core Center and the University of Cincinnati Office of Research. One author disclosed a consulting relationship with LEO Pharma.

Source: shahin, M.M., et al. (2025). Published online July 31,2025,in Pediatric Dermatology. https://onlinelibrary.wiley.com/doi/10.1111/pde.16039

Upadacitinib Shows Promise in Treating Systemic Sclerosis-Associated Interstitial Lung Disease

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Upadacitinib Shows Promise in Treating Systemic Sclerosis-Associated Interstitial Lung Disease

A recent clinical trial has revealed that the JAK inhibitor upadacitinib demonstrates effectiveness in treating systemic sclerosis-associated interstitial lung disease (SSc-ILD). The study, presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 annual Meeting, indicates that upadacitinib reduces the rate of decline in forced vital capacity (FVC) in patients with SSc-ILD, compared to the current standard treatment, mycophenolate mofetil.

Upadacitinib Outperforms Standard Treatment in Lung Function preservation

The research, led by Dr. Manal Hassanien from Assiut University, Egypt, showed that after one year, the difference in the annual rate of decline in FVC between the upadacitinib and mycophenolate groups was 20.9 mL/year, favoring upadacitinib (P = .05).This suggests a meaningful benefit in preserving lung function for patients treated with upadacitinib.

Did You Know? Forced vital capacity (FVC) is the maximum amount of air a person can exhale after a maximum inhalation. It’s a key indicator of lung function.

The double-blinded, randomized study involved 57 patients with SSc, with disease onset of more than 3 years. All participants had an FVC less than 75% of the predicted normal value and evidence of lung fibrosis. Patients were administered either 15 mg of upadacitinib daily or 2000 mg of mycophenolate daily.

Detailed Study Results: FVC and DLCO Improvements

After 52 weeks, a decline of ≥ 5% in FVC from baseline was observed in 20.6% of the upadacitinib group, compared to 37.5% in the mycophenolate group. Furthermore,a 10% drop in FVC from baseline at 1 year was more common in patients taking mycophenolate (17.9%) than in those taking upadacitinib (6.8%).

Changes in diffusing capacity of the lungs for carbon monoxide (DLCO) at 52 weeks were also more favorable in the upadacitinib group (-62.7 mL) compared to the mycophenolate group (-93.3 mL). DLCO measures how well the lungs transfer gas from inhaled air to the bloodstream, providing another critical measure of lung health according to the american Thoracic Society.

Pro tip: Monitoring FVC and DLCO regularly can definitely help track the progression of SSc-ILD and assess the effectiveness of treatments.

Expert Commentary and Future Considerations

Dr. Iulia Szabo, a rheumatologist at “Iuliu Haţieganu” University of Medicine and Pharmacy, Romania, commented on the study, calling the results “really promising.” she noted that previous studies have shown encouraging evidence using other JAK inhibitors in SSc-ILD treatment, although the data were mostly experimental.

Szabo also cautioned that the younger age of participants in the study may mean that older patients could experience a higher risk of adverse events associated with JAK inhibitors.”The problem we might have will be with older patients as we certainly know all the adverse effects that JAK inhibitors have, and probably we should be a bit more cautious,” she said.

Current Treatment Landscape and Upadacitinib’s Potential Role

Currently, upadacitinib is FDA-approved for various conditions, including rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease. However,for SSc-ILD,nintedanib and tocilizumab remain the only FDA-approved treatments. The findings from this study suggest that upadacitinib could potentially become another valuable option for managing this challenging condition.

Key metrics: Upadacitinib vs. Mycophenolate in SSc-ILD Treatment
Metric	Upadacitinib	Mycophenolate
Annual FVC decline Difference	Favored Upadacitinib (20.9 mL/year)	–
≥ 5% FVC Decline at 52 Weeks	20.6%	37.5%
10% FVC Drop at 1 Year	6.8%	17.9%
DLCO Change at 52 Weeks	-62.7 mL	-93.3 mL

What are your thoughts on the potential of upadacitinib for treating SSc-ILD?

How might these findings impact treatment strategies for patients with systemic sclerosis?

Evergreen Insights on Systemic Sclerosis-Associated Interstitial Lung Disease

Systemic sclerosis (SSc), also known as scleroderma, is a chronic autoimmune disease characterized by hardening and tightening of the skin and connective tissues. Interstitial lung disease (ILD) is a common and serious complication of SSc, affecting a significant proportion of patients. SSc-ILD can lead to progressive scarring of the lungs, resulting in shortness of breath, reduced exercise capacity, and ultimately, respiratory failure.

The management of SSc-ILD typically involves immunosuppressive medications aimed at reducing inflammation and slowing the progression of lung damage.however, current treatments have limitations, and new therapeutic options are needed to improve outcomes for patients with this debilitating condition. The emergence of JAK inhibitors like upadacitinib offers a promising avenue for future treatment strategies.

Frequently Asked Questions About Upadacitinib and SSc-ILD

Is upadacitinib a cure for systemic sclerosis-associated interstitial lung disease?: No, upadacitinib is not a cure for SSc-ILD. However, it may help to slow the progression of the disease and improve lung function.
How long does it take to see results with upadacitinib for SSc-ILD?: The clinical trial showed improvements in lung function within 52 weeks of treatment. Individual results may vary.
Are there any side effects associated with upadacitinib?: Yes,like all medications,upadacitinib can cause side effects. Common side effects may include infections, nausea, and headache. It is indeed critically important to discuss potential side effects with your healthcare provider.
Can upadacitinib be used in combination with other treatments for SSc-ILD?: The safety and efficacy of upadacitinib in combination with other treatments for SSc-ILD have not been fully established. Your healthcare provider can determine the best treatment approach for your individual situation.
Where can I find more information about systemic sclerosis-associated interstitial lung disease?: You can find more information about SSc-ILD from reputable sources such as the Scleroderma Foundation and the American Lung Association.

Disclaimer: This article provides information for general knowledge and awareness only. It does not constitute medical advice and should not be substituted for professional consultation with a qualified healthcare provider.

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juvenile rheumatoid arthritis; juvenile RA; juvenile idiopathic arthritis; juvenile rheumatoid arthritis (JRA); juvenile idiopathic arthritis (JIA); JIA; JRA

Delayed Psoriasiform Dermatitis in Children Treated with TNF Inhibitors