A recent study comparing the safety profiles of Janus kinase inhibitors (JAKi) in adolescent and adult patients has revealed notable differences in the types of adverse events (AEs) reported across age groups. The research, led by Sahithi Talasila from Sidney Kimmel Medical College at Thomas Jefferson University, analyzed data from the FDA's Adverse Event Reporting System (AERS) and CVAROD databases to evaluate the safety of five JAK inhibitors approved for pediatric use: upadacitinib, baricitinib, ruxolitinib, abrocitinib, and tofacitinib. The findings indicate that pediatric patients report higher numbers of lymphatic and blood disorders, while adults report more issues with the nervous and musculoskeletal systems.
The study, which examined AE reports from November 2011 to February 2023, included data from 133,216 adult patients and 955 pediatric patients. The research team extracted AE reports related to the five JAK inhibitors and classified them based on the Medical Dictionary for Regulatory Activities (MedDRA) system organ class. They then calculated combined proportions of AEs for each age group to identify trends.
Key Findings in Adult Patients
Among adult patients, the most common AE categories were infections (16.8%), general administration issues and symptoms (13.5%), musculoskeletal and connective tissue problems (7.04%), gastrointestinal system issues (5.8%), and nervous system disorders (5.0%). Infections were the most frequently reported concern in this age group.
Key Findings in Pediatric Patients
In the pediatric cohort, the major AE categories were blood and lymphatic system disorders (24.0%), infections (17.2%), pyrexia, fatigue, and other general symptoms (15.7%), gastrointestinal-related disorders (13.6%), and respiratory problems (5.3%). Notably, ruxolitinib-related AEs in children mainly involved blood and lymphatic system issues (35.2%), a higher incidence than in adults (8.9%). Baricitinib use in children was associated with a greater proportion of gastrointestinal and respiratory events compared to adults, where infections were more frequent. Upadacitinib and abrocitinib use in children also showed a high percentage of infections, particularly with abrocitinib, where blood and lymphatic system disorders were more prevalent.
Implications for Clinical Practice
Despite the variations in AE profiles, the researchers concluded that overall AE patterns for both age cohorts had substantial overlap. "JAKi are increasingly recognized as largely safe and effective treatments for cutaneous and extracutaneous disease," the team wrote. "In this study, we describe AEs associated with commercially available JAKi and detected some variation in those reported for children compared to adults."
The study highlights the importance of considering age-related differences in safety profiles when prescribing JAK inhibitors. While the drugs are generally considered safe and effective, clinicians should be aware of the potential for different types of AEs in pediatric versus adult patients. Further research is needed to fully understand the underlying mechanisms driving these differences and to optimize treatment strategies for both populations.
