A56: Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab
Bibliographic record
Abstract
Background/Purpose: Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA). Changes in therapies, including biologics, may trigger MAS. Interleukin‐6 (IL‐6) plays a major pathogenic role in sJIA; data in animals suggest that high IL‐6 levels contribute to the triggering of MAS. Treatment with the IL‐6 receptor inhibitor tocilizumab (TCZ) is very effective in patients with sJIA. In this study, we investigated the rates and features of MAS occurring during TCZ treatment in patients with sJIA. Methods: Data were collected from patients with sJIA treated with TCZ in the international phase 3 trial (TENDER), 4 clinical trials in Japan, and the Japanese postmarketing surveillance (JPMS) program. Reported MAS events or disease flares associated with alanine aminotransferase/aspartate aminotransferase (ALT/AST) elevations were collected. Worksheets with event information were assessed by an independent panel (2 pediatric rheumatologists, 1 pediatric hematologist with MAS expertise) overseen by the TENDER lead investigator. Cases were adjudicated as definite MAS, potential MAS, not MAS, or insufficient data. Results: The data set included 112 patients from TENDER (403.0 patient‐years' [PY] exposure to TCZ), 149 patients from the Japanese trials (326 PY), and 366 patients from the JPMS program (523.9 PY). Of 31 cases reviewed, 22 events were adjudicated as definite or potential MAS: 5 from TENDER (3 definite, 2 potential), 6 from the Japanese trials (3 definite, 3 potential), and 11 from the JPMS program (5 definite, 6 potential). The rates/100 PY of definite/potential MAS were 1.24 (95% CI, 0.4–2.90) in TENDER, 1.84 (95% CI, 0.68–4.00) in the Japanese trials, and 2.10 (95% CI, 1.05–3.76) in the JPMS program. Features contributing to the adjudication of definite MAS are listed in the . All 11 events adjudicated as definite MAS met the preliminary MAS diagnostic guidelines. All definite and potential MAS resolved with the exception of MAS in a patient from the Japanese phase 3 study who died after respiratory/cardiac arrest. Criteria for Adjudication of Cases as Definite MAS (n = 11) Features of MAS Patients for Whom These Features Led to Adjudication of Definite MAS n (%)mg Clinical signs Fever 6 (55) Rash 3 (27) Hemorrhage with purpura, hematuria 2 (18) Hepatomegaly 0 (0) Laboratory features Elevated ALT/AST 11 (100) Thrombocytopenia 9 (82) Elevated ferritin 8 (73) Leukopenia 7 (64) Neutropenia 6 (55) Elevated lactate dehydrogenase 4 (36) Low fibrinogen 4 (36) Increased triglycerides 4 (36) Elevated D‐dimers 3 (27) Low hemoglobin 4 (36) Elevated C‐reactive protein 2 (18) Low erythrocyte sedimentation rate 2 (18) a Thresholds for abnormal values were determined according to age and local guidelines. Conclusion: The use of TCZ does not appear to be associated with increased risk for MAS in sJIA. There were no unusual clinical or laboratory features in these MAS cases.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".