Tumor Necrosis Factor Inhibitors Safely, Effectively Treat Patients With Juvenile Idiopathic Arthritis

A systematic literature review (SLR) revealed that tumor necrosis factor inhibitors (TNF) are both effective and well-tolerated in the treatment of juvenile idiopathic arthritis (JIA), according to research published in Pediatric Rheumatology.¹ However, investigators noted that additional, more long-term studies, particularly when patients transition from pediatric to adult care, are needed.

Gerd Horneff, MD, PhD

Image Credit: ResearchGate

“To date, no head-to-head trials have compared outcomes with different bDMARDs, especially TNFs, in JIA,” Gerd Horneff, MD, PhD, Department of General Paediatrics at the Asklepios Clinic Sankt Augustin, Germany, and a team of investigators, explained. “[However], several meta-analyses and systematic reviews of the efficacy and/or safety of these agents have been published.”

JIA can cause both short- and long-term disability, growth issues, gastrointestinal symptoms, depression, and fatigue. Roughly half of children who develop JIA continue to experience active disease into adulthood, affecting physical function as well as health-related quality of life.²

Eligible studies were identified through online searches of PubMed, MEDLINE, and Embase databases, with a cutoff date of March 16, 2021. Abstracts were also identified from recent meetings, including the American College of Rheumatology (ACR) Convergence, European League Against Rheumatism (EULAR), Childhood Arthritis and Rheumatology Research Alliance, and the Paediatric Rheumatology European Society.

Outcome data were extracted if the cohort of patients treated with TNF included 30 or more participants. Efficacy was determined using the JIA-ACR response criteria, while safety was evaluated by calculating the incidence of serious adverse events (SAEs) per 100 patient-years (100PY).

Of the 87 publications included in qualitative synthesis, 19 publications described 13 clinical trials. Most were from Europe (n = 48), multiregional areas (n = 17), and North America (n = 11). The duration of treatment ranged from 12 to 224 weeks, with open-label extensions up to 8 years. TNFs evaluated in these trials included etanercept, golimumab, adalimumab, and infliximab.

In the golimumab cohort, achievement of JIA-ACR30/50/70/90 at week 16 was observed in 89%, 79%, 66%, and 36% of patients, respectively. For those receiving etanercept, JIA-ACR30/50/70/90 was reported in 73 – 94%, 53 – 78%, 36 – 59%, and 28% of patients, respectively, at week 12. Patients in the adalimumab cohort (either monotherapy or concomitant methotrexate) achieving these response rates ranged from 71 – 94%, 68 – 90%, 55 – 61%, and 39 – 42%, respectively, at week 12. Patients treated with infliximab (3 mg/kg in combination with methotrexate) achieved JIA-ACR30/50/70 at rates of 64%, 50%, and 22%, respectively, at week 14. JIA-ACR90 was not reported for this medication.

Regarding safety data, the SAE incidence across all time points ranged from 0 – 13.7 SAE/100PY for patients receiving adalimumab, 10.4 – 24.3 SAE/100PY in the golimumab cohort, and 0 – 20.0 SAE/100PY for those treated with etanercept. The SAE incidence could not be estimated for infliximab.

In addition to the known limitations of an SLR, the heterogeneity of the studies prevented direct comparisons of evidence. Additonally, investigators were unable to compare baseline disease severity among patients. Lastly, while limiting study eligibility to 30 or more patients treated with a TNF was designed to increase the robustness of the analysis, it may have excluded potentially useful data.

“The published evidence suggests that adalimumab, etanercept, golimumab, and infliximab are effective and well-tolerated treatments for JIA,” investigators concluded. “This SLR could serve as the basis for a dedicated meta-analysis of the efficacy and safety of TNFs in JIA, as well as a future SLR dedicated to functional and quality of life outcomes that would provide more precise guidance for the optimal use of TNFs in JIA.”

References

1. ^{Horneff G, Minden K, Rolland C, Daly ACH, Borlenghi C, Ruperto N. Efficacy and safety of TNF inhibitors in the treatment of juvenile idiopathic arthritis: a systematic literature review. Pediatr Rheumatol Online J. 2023;21(1):20. Published 2023 Feb 24. doi:10.1186/s12969-023-00798-8}
2. ^{Hersh A, von Scheven E, Yelin E. Adult outcomes of childhood-onset rheumatic diseases. Nat Rev Rheumatol. 2011;7(5):290–5.}