Background The “comparison of STep-up and step-down therapeutic strategies in childhood ARthritiS” (STARS) trial aims to investigate whether an early aggressive therapeutic intervention, based on the initial start of synthetic and biologic DMARDs (Step-down strategy), is superior to an approach based on treatment escalation conducted following the treat-to-target principle (Step-up strategy), in children with Juvenile idiopathic arthritis (JIA). Objectives This randomised clinical trial aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs. The aim of this study is to compare: • the demographic data of patients enrolled in the STARS trial; • the frequency of inactive disease and the JADAS-based disease status between the two arms at 6 months; • the AE incidence rate by drug. Methods Patients with recent-onset oligoarthritis or rheumatoid factor negative polyarthritis JIA who were ≤17 years old at diagnosis and drug-naïve could be enrolled in the STARS trial. Enrollment occurred between May 2019 and October 2024. Follow-up was completed in November 2025. Disease activity assessments, medication start and stop dates, and severe adverse events/events of special interest reporting were collected for STARS trial participants at 3, 6, 9, and 12 months. After the screening visit, patients were randomised into two treatment arms: “Step-up” and “Step-down”. Patients in the Step-up arm were treated according to a conventional strategy based on treatment escalation and driven by the treat-to-target strategy. Patients in the Step-down arm were treated with an early, combined, aggressive therapy for 6 months; in both arms, the treatment was based on the severity of the disease. Children with oligoarthritis without features of poor prognosis (according to the 2011 American College of Rheumatology) were considered as “less severe patients”, children with RF-negative arthritis and children with oligoarthritis and features of poor prognosis will be considered as “more severe patients”. The level and state of disease activity was measured in all patients at each step of the study by means of the JADAS10. After completing data collection of all visits of study children from baseline to the primary endpoint assessment, a preliminary analysis of endpoints at six months will be performed. The frequency of inactive disease and the JADAS-based disease status will be compared at six months between the two arms in the whole cohort and after stratifying by disease severity group. We chose to use the 6-month endpoint as preliminary data in order to include data from all enrolled patients. Complete 12-month data for all patients are not yet available, and this would have resulted in missing data. Results A total of 240 JIA patients were enrolled. Nine patients did not receive allocated interventions and they were excluded from the analysis. Of the 231 analyzable participants, 116 (50.2%) and 115 (49.8%) were started on the step-up and step-down arm respectively. Eight patients (3.4%) were lost to follow-up before the 6-month visit. That left 223 patients who continued with follow-up at the registry site for at least 6 months (112 Step-up, 111 Step-down). The demographic and disease features of subjects two arms were homogeneous, particularly in terms of disease severity. There were no clinically relevant differences in baseline disease characteristics, including JIA category, clinical JADAS-10 score, number of joints with active disease, erythrocyte sedimentation rate and physician global assessment of disease activity. JADAS-10 and clinical JADAS-10 scores improved over time in all participants and the majority (66.8%) achieving inactive disease at 6 months (median 0.5). ID according to the JADAS-10 was achieved at 6 months by an estimated 55.4% of participants on the Step-up arm, and 78.4% of participants on the Step-down arm Seventy-seven and six participants experienced 137 adverse events (AEs) and 6 serious AE (SAEs), respectively. No deaths were reported. Conclusions The STARS trial is the first Italian multicenter randomized study to evaluate two different treatment strategies (Step-down vs. Step-up) in patients with JIA in a treat-to-target setting. For the purposes of this study, we chose to adopt a shorter primary endpoint by comparing the frequency of patients achieving inactive disease at 6 months after the first therapeutic intervention between the two arms. Subsequently we will evaluate the more robust primary endpoint by comparing the frequency of clinical remission at the end of the study, defined as maintaining inactive disease status for at least 6 consecutive months. If confirmed in the primary endpoint analysis, our results, suggest that a strategy combining early initiation of bDMARDs with a treat-to-target approach may be even more effective and could provide important evidence supporting the concept of the so-called “window of opportunity”. The STARS dataset represents a unique and rich resource of highly curated data on a large cohort of patients with newly diagnosed JIA, which will answer additional questions through further data analysis and long-term follow-up.
The “Comparison of STep-up and step-down therapeutic strategies in childhood ARthritiS” (STARS) trial: patients’ outcome at six months
BURRONE, MARCO
2026-05-27
Abstract
Background The “comparison of STep-up and step-down therapeutic strategies in childhood ARthritiS” (STARS) trial aims to investigate whether an early aggressive therapeutic intervention, based on the initial start of synthetic and biologic DMARDs (Step-down strategy), is superior to an approach based on treatment escalation conducted following the treat-to-target principle (Step-up strategy), in children with Juvenile idiopathic arthritis (JIA). Objectives This randomised clinical trial aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs. The aim of this study is to compare: • the demographic data of patients enrolled in the STARS trial; • the frequency of inactive disease and the JADAS-based disease status between the two arms at 6 months; • the AE incidence rate by drug. Methods Patients with recent-onset oligoarthritis or rheumatoid factor negative polyarthritis JIA who were ≤17 years old at diagnosis and drug-naïve could be enrolled in the STARS trial. Enrollment occurred between May 2019 and October 2024. Follow-up was completed in November 2025. Disease activity assessments, medication start and stop dates, and severe adverse events/events of special interest reporting were collected for STARS trial participants at 3, 6, 9, and 12 months. After the screening visit, patients were randomised into two treatment arms: “Step-up” and “Step-down”. Patients in the Step-up arm were treated according to a conventional strategy based on treatment escalation and driven by the treat-to-target strategy. Patients in the Step-down arm were treated with an early, combined, aggressive therapy for 6 months; in both arms, the treatment was based on the severity of the disease. Children with oligoarthritis without features of poor prognosis (according to the 2011 American College of Rheumatology) were considered as “less severe patients”, children with RF-negative arthritis and children with oligoarthritis and features of poor prognosis will be considered as “more severe patients”. The level and state of disease activity was measured in all patients at each step of the study by means of the JADAS10. After completing data collection of all visits of study children from baseline to the primary endpoint assessment, a preliminary analysis of endpoints at six months will be performed. The frequency of inactive disease and the JADAS-based disease status will be compared at six months between the two arms in the whole cohort and after stratifying by disease severity group. We chose to use the 6-month endpoint as preliminary data in order to include data from all enrolled patients. Complete 12-month data for all patients are not yet available, and this would have resulted in missing data. Results A total of 240 JIA patients were enrolled. Nine patients did not receive allocated interventions and they were excluded from the analysis. Of the 231 analyzable participants, 116 (50.2%) and 115 (49.8%) were started on the step-up and step-down arm respectively. Eight patients (3.4%) were lost to follow-up before the 6-month visit. That left 223 patients who continued with follow-up at the registry site for at least 6 months (112 Step-up, 111 Step-down). The demographic and disease features of subjects two arms were homogeneous, particularly in terms of disease severity. There were no clinically relevant differences in baseline disease characteristics, including JIA category, clinical JADAS-10 score, number of joints with active disease, erythrocyte sedimentation rate and physician global assessment of disease activity. JADAS-10 and clinical JADAS-10 scores improved over time in all participants and the majority (66.8%) achieving inactive disease at 6 months (median 0.5). ID according to the JADAS-10 was achieved at 6 months by an estimated 55.4% of participants on the Step-up arm, and 78.4% of participants on the Step-down arm Seventy-seven and six participants experienced 137 adverse events (AEs) and 6 serious AE (SAEs), respectively. No deaths were reported. Conclusions The STARS trial is the first Italian multicenter randomized study to evaluate two different treatment strategies (Step-down vs. Step-up) in patients with JIA in a treat-to-target setting. For the purposes of this study, we chose to adopt a shorter primary endpoint by comparing the frequency of patients achieving inactive disease at 6 months after the first therapeutic intervention between the two arms. Subsequently we will evaluate the more robust primary endpoint by comparing the frequency of clinical remission at the end of the study, defined as maintaining inactive disease status for at least 6 consecutive months. If confirmed in the primary endpoint analysis, our results, suggest that a strategy combining early initiation of bDMARDs with a treat-to-target approach may be even more effective and could provide important evidence supporting the concept of the so-called “window of opportunity”. The STARS dataset represents a unique and rich resource of highly curated data on a large cohort of patients with newly diagnosed JIA, which will answer additional questions through further data analysis and long-term follow-up.
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