Macrophage activation syndrome (MAS) is a severe hyperinflammatory state that complicates pediatric rheumatic diseases, most commonly systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus. MAS features excessive T-cell activation and high interferon-γ (IFN-γ) production, driving hemophagocytic macrophage activation and multisystem organ dysfunction. Current treatment paradigms rely heavily on high-dose glucocorticoids, but prolonged use carries substantial adverse effects. Cytokine-directed biologics and etoposide-based HLH regimens have roles in selected settings, while ruxolitinib, a JAK1/2 inhibitor, can suppress IFN-γ and other proinflammatory signaling and has emerged as a potential treatment for MAS.
This study sought to evaluate the efficacy and safety of ruxolitinib in pediatric rheumatic disease–associated MAS (RD-MAS) in a real-world tertiary-care cohort.
Investigators performed a retrospective review of medical records at Shenzhen Children’s Hospital covering January 2021 through December 2025. Eligible patients met all of the following: a confirmed rheumatic disease diagnosis; MAS defined by the 2016 EULAR/ACR classification criteria for MAS in sJIA; complete clinical and laboratory documentation; detailed treatment records; and a minimum of one year of follow-up. Exclusion criteria included malignancy, monogenic autoinflammatory syndromes, and active infection.
Because randomized trials are difficult for MAS, patients treated with ruxolitinib plus conventional immunosuppression were compared with contemporaneous controls who received conventional immunosuppressive therapy alone. The decision to use ruxolitinib was at treating physicians’ discretion and influenced by disease persistence, inadequate prior response, recurrent activity during steroid tapering, drug accessibility, and patient financial capacity. Ethical approval and a waiver for re-obtaining consent were obtained from the hospital ethics committee.
Data collected included clinical manifestations, laboratory tests (WBC, neutrophils, platelets, hemoglobin, ESR, CRP, ferritin, fibrinogen, ALT, AST, LDH), and serum cytokines (IFN-γ, IL-6, IL-10, TNF-α, IL-4, IL-2). Treatment data encompassed glucocorticoids, immunosuppressants, biologics, and IVIG. Baseline was defined at RD-MAS diagnosis prior to the regimen under study; follow-up time points included weeks 2, 4, 8, 12, 24, and 48.
Primary outcome: time to complete remission (CR). Secondary outcomes: remission rates over follow-up, laboratory responses, the glucocorticoid-sparing effect, cumulative glucocorticoid exposure, and adverse events. Response categories were CR (clinical resolution and normalization of parameters), PR (improvement in at least two predefined clinical/laboratory parameters, including ≥50% ferritin reduction and neutrophil recovery), and NR (neither CR nor PR). Statistical methods used included descriptive statistics, group comparisons (Welch’s t-test, Mann–Whitney U, chi-square/Fisher exact), Kaplan–Meier analysis for time to CR, and a linear mixed-effects model for longitudinal glucocorticoid dose changes. Multivariable adjustment was not performed because of limited sample size.
Twenty-one pediatric patients met inclusion criteria: 10 received ruxolitinib (ruxo group) and 11 received conventional therapy alone (control group). In the ruxo group, median age at RD-MAS onset was 8.9 years; diagnoses were predominantly sJIA (7/10), with single cases of SLE and other connective tissue diseases. All ruxo patients presented with fever; bone marrow hemophagocytosis was seen in 20% and multilineage cytopenia in 30%.
Baseline laboratory patterns were consistent with MAS: markedly elevated ferritin (median 4112.9 ng/mL in ruxo group), elevated liver enzymes and LDH in many patients. Compared with controls, the ruxo group had significantly higher WBC and neutrophil counts and lower AST; other major MAS features were comparable between cohorts.
Ruxolitinib was administered in addition to conventional immunosuppressive and biologic agents as clinically indicated. Concomitant therapies in the ruxo group included canakinumab (n = 4), tocilizumab (n = 5), methotrexate (n = 3), cyclophosphamide (n = 3), and mycophenolate mofetil (n = 1). IVIG was used in three ruxo patients. The control group received glucocorticoids plus a mix of biologics and DMARDs, including tocilizumab, canakinumab, methotrexate, mycophenolate, and belimumab.
Among the 10 patients treated with ruxolitinib, 30% (3/10) achieved CR by week 4, and all patients achieved CR by week 48. Time-to-CR analysis did not show a statistically significant difference between ruxo and control groups according to the report. Remission rates and laboratory normalization were reported across follow-up visits; specific time-to-event curves and numerical p values were provided in the primary tables and figures of the source report.
The ruxolitinib group demonstrated a pronounced steroid-sparing pattern. Median prednisone-equivalent dose in ruxo patients fell from 4 mg/kg/day at baseline to 0.4 mg/kg/day by week 8. All ruxo patients successfully discontinued glucocorticoids by week 48 while maintaining remission. The ruxolitinib group had significantly lower cumulative glucocorticoid exposure over follow-up compared with the non-ruxolitinib group, as assessed in the study. A linear mixed-effects model was applied to longitudinal steroid dosing to evaluate interactions between group and time.
The study reports no significant difference in infection rates between the ruxolitinib and control groups. Beyond reporting comparable infection rates and stating favorable safety in the cohort, the source text does not provide granular adverse event tables or detailed safety-event descriptions in the extracted sections. No specific drug-related serious adverse events were described in the provided text.
In this retrospective pediatric RD-MAS cohort, ruxolitinib-based therapy was associated with sustained disease control and a substantial glucocorticoid-sparing effect, including complete steroid discontinuation in all ruxo patients by week 48. Time to complete remission and infection rates were not significantly different between groups, but cumulative glucocorticoid exposure was significantly lower with ruxolitinib.
Limitations inherent to the study include its retrospective design, small sample size (n = 21), inability to perform multivariable adjustment, selection bias due to physician discretion and access/financial factors influencing ruxolitinib use, heterogeneity of underlying rheumatic diagnoses and concomitant therapies, and incomplete reporting of detailed adverse-event data in the provided text. The authors conclude that ruxolitinib may be a promising steroid-sparing option for pediatric RD-MAS but emphasize that larger prospective studies are needed to confirm efficacy and safety.
(Details not reported in the source: dosing schedules beyond summary entries for individual patients, granular adverse-event listings, and formal statistical values for some comparisons were not provided in the extracted text.)