Pediatric Clinical Year in Review: 2023

Updates in pediatric rheumatology presented at ACR Convergence 2023

Stacy Ardoin, MD

SAN DIEGO—Too many excellent pediatric rheumatology studies to squeeze into one talk? What a good problem to have. This year at ACR Convergence 2023, Stacy Ardoin, MD, MSc, professor, Division of Rheumatology and Immunology, Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, presented an excellent overview of clinical updates in pediatric rheumatology from November 2022–November 2023.

In selecting studies to present, she sought to strike a balance between those that could affect patient outcomes, those that included practical information for the clinician and those that shared novel information.

Clinical Trials

Dr. Ardoin first highlighted some key clinical trials. She touched on baricitinib in juvenile idiopathic arthritis (JIA), which, in a phase 3 trial, decreased the time to disease flare compared with placebo (HR 0.241 [95% confidence interval 0.128–0.453]). As expected, treatment-emergent infections were significantly higher in the baricitinib group, but only two were classified as serious. One patient in the baricitinib group (n=82) developed a pulmonary embolism that was attributed to the drug.¹

Next, she discussed emapalumab in the treatment of patients with systemic JIA or adult-onset Still’s disease who develop macrophage activation syndrome (MAS). Emapalumab is an anti-interferon-gamma monoclonal antibody that is approved by the U.S. Food & Drug Administration (FDA) for the treatment of primary hemophagocytic lymphohistiocytosis (HLH). In this prospective study, emapalumab led to MAS remission in 13 of 14 patients at a median time of 25 days in patients whose high-dose glucocorticoids (GC) had failed to help.²

Last, she mentioned a small study that showed that abatacept led to improvement in disease activity in nine of 10 patients with refractory juvenile dermatomyositis. “This study was important to include [because] we have so few clinical trials in juvenile dermatomyositis,” Dr. Ardoin said.³

Practice Guidance: Vaccines

This year also saw some key updates to vaccine recommendations for pediatric patients with autoimmune and inflammatory rheumatic diseases from both the European Alliance of Associations for Rheumatology/Paediatric Rheumatology European Society (EULAR/PRES) and the ACR.^4,5 “EULAR/PRES really focused on expanded allowing for the use of the measles mumps rubella (MMR) booster and varicella zoster vaccine, both of which we know are live virus vaccines,” Dr. Ardoin explained. “Recent studies have shown that these vaccines can be used safely in patients taking methotrexate. Use can also be considered in those taking tumor necrosis factor-alpha inhibitors, interleukin-1 or interleukin-6 inhibitors, and low-dose glucocorticoids.”

The ACR guidelines gave no specific recommendations on the use of these live vaccines but did recommended holding methotrexate for two weeks after flu vaccine to increase immunogenicity if possible.

Although she didn’t have time to cover them in detail, Dr. Ardoin also encouraged the audience to take a look at new practice guidelines pertaining to HLH/MAS, uveitis and quality measures in patients with JIA.^6–8

Systemic JIA & Lung Disease

Dr. Ardoin turned next to systemic JIA and interstitial lung disease (ILD), noting, “Several publications this year added to our understanding of this very concerning complication.” Perhaps most useful was the development of a screening algorithm for lung disease in systemic JIA by investigators at Boston Children’s Hospital.⁹ If any of nine red flag features (e.g., eosinophilia or clubbing) are present, consider referral to pulmonary clinic and complete pulmonary function tests (spirometry, lung volumes, diffusing capacity and six-minute walk testing). Red flag features increase the risk of developing ILD.

Mental Health

Dr. Ardoin took care to mention two studies demonstrating the increased risk of mental health disorders in patients with JIA.^10,11 “As you all know, we’ve had robust literature that has told us about the impact of mental health on people with lupus, but not as much in JIA,” she said. “I think these studies really demonstrate that we need more studies to make sure JIA patients are adequately cared for, too.”

Natural History

On a more upbeat note, comparison of two JIA inception cohorts (2005 to 2010, and 2017 to 2021) showed that we’re on the right track when it comes to treatment.¹² “These data show that over 16 years, we have had significant improvements in the outcomes of our patients with the use of conventional and biologic disease modifying anti-rheumatic drugs.” The usage of these drugs increased, as did the amount of patients with minimally active or inactive JIA.

Musculoskeletal Ultrasound

Although she lacked time to go into detail, Dr. Ardoin gave a shoutout to colleagues focused on musculoskeletal ultrasound research. “They are really working diligently to develop protocols, a scoring system and an evidence base that will allow us to use this tool in the future to better characterize our patients,” she said. “There is also the potential to use musculoskeletal ultrasound findings as outcome measures in clinical trials.”^13–15

Workforce Shortage & Access to Care

Dr. Ardoin closed with a study that confirms something that any rheumatologist, be it pediatric or adult, knows: not all rheumatology referrals are created equal. At a large pediatric referral center, only 23% of 2,638 new patient referrals were diagnosed with rheumatic disease, and of the positive anti-nuclear antibody (ANA) referrals, only 7% had rheumatic disease.¹⁶ “This information probably doesn’t come as a surprise,” Dr. Ardoin said. “In a time when we are facing a significant workforce shortage, data like these suggest that efforts to reduce unnecessary referrals by educating referring providers may help us increase access.”

Samantha C. Shapiro, MD, is the executive editor of Harrison’s Principles of Internal Medicine. As a clinician educator, she practices telerheumatology and writes for both medical and lay audiences.

References

1. Ramanan AV, Quartier P, Okamoto N, et al. Baricitinib in juvenile idiopathic arthritis: An international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial. Lancet. 2023 Aug 12;402(10401):555–570.
2. De Benedetti F, Grom AA, Brogan PA, et al. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann Rheum Dis. 2023 Jun;82(6):857–865.
3. Curiel R V., Nguyen W, Mamyrova G, et al. Improvement in disease activity in refractory juvenile dermatomyositis following abatacept therapy. Arthritis Rheumatol. 2023 Jul;75(7):1229–1237.
4. Bass AR, Chakravarty E, Akl EA, et al. 2022 American College of Rheumatology guideline for vaccinations in patients with rheumatic and musculoskeletal diseases. Arthritis Care Res (Hoboken). 2023 Mar;75(3):449–464.
5. Jansen MHA, Rondaan C, Legger GE, et al. EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: Update 2021. Ann Rheum Dis. 2023 Jan;82(1):35–47.
6. Bingham CA, Harris JG, Qiu T, et al. Pediatric Rheumatology Care and Outcomes Improvement Network’s quality measure set to improve care of children with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2023 Dec;75(12):2442–2452.
7. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023 Oct;82(10):1271–1285.
8. Foeldvari I, Maccora I, Petrushkin H, et al. New and updated recommendations for the treatment of juvenile idiopathic arthritis–associated uveitis and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken). 2023 May;75(5):975–982.
9. Wobma H, Bachrach R, Farrell J, et al. Development of a screening algorithm for lung disease in systemic juvenile idiopathic arthritis. ACR Open Rheumatol. 2023 Oct;5(10):556–562.
10. Delcoigne B, Horne AC, Reutfors J, Askling J. Risk of psychiatric disorders in juvenile idiopathic arthritis: Population- and sibling-controlled cohort and cross-sectional analyses. ACR Open Rheumatol. 2023 May;5(5):277–284.
11. Li L, Merchant M, Gordon S, et al. High rates of symptoms of major depressive disorder and panic disorder in a Canadian sample of adolescents with juvenile idiopathic arthritis. J Rheumatol. 2023 Jun;50(6):804–808.
12. Nguyen K, Barsalou J, Basodan D, et al. A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: Results from ReACCh-Out and the CAPRI registry. Rheumatology (Oxford). 2023 Oct 18:kead560.
13. Collado P, Martire MV, Lanni S, et al. OMERACT international consensus for ultrasound definitions of tenosynovitis in juvenile idiopathic arthritis: Systematic literature review and delphi process. Arthritis Care Res (Hoboken). 2023 Nov;75(11):2277–2284.
14. Vega-Fernandez P, Oberle EJ, Henrickson M, et al. Musculoskeletal ultrasound and the assessment of disease activity in juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2023 Aug;75(8):1815–1820.
15. Vega-Fernandez P, Esteban Y, Oberle E, et al. Reliability of the pediatric specific musculoskeletal ultrasound scoring systems for the elbow, wrist, and finger joints. Journal of Rheumatology. 2023 Feb;50(2):236–239.
16. Reiff DD, Bridges JM, Rife EC, et al. Majority of new patient referrals to a large pediatric rheumatology center result in non-rheumatic diagnosis. Pediatr Rheumatol Online J. 2023 Oct 13;21(1):120.