Tocilizumab May Modify Clinical, Laboratory Features of Macrophage Activation Syndrome in Systemic JIA

pediatrician talking to patient
pediatrician talking to patient
Researchers determined the effect of tocilizumab on the clinical and laboratory features of macrophage activation syndrome in patients with complicating systemic juvenile idiopathic arthritis.

Tocilizumab may modify clinical and laboratory features of macrophage activation syndrome (MAS) in pediatric patients with systemic juvenile idiopathic arthritis (JIA), according to study results published in Pediatric Rheumatology.

Investigators conducted a case-control study of patients with systemic JIA diagnosed with MAS between 2006 and 2017 at 1 of 14 institutes of pediatric rheumatology in Japan. They extracted laboratory data, including platelet count, serum aspartic aminotransferase levels, serum ferritin levels, serum triglyceride levels, and serum fibrinogen levels, from patient records. A panel of 15 rheumatology experts was presented with the data and asked to classify patient profiles with and without MAS based on clinical and laboratory features at the time of disease onset. The minimum required agreement between experts was set at 80%. Researchers assessed MAS according to 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. They defined possible MAS as having characteristic laboratory features but no clinical features, and defined full-blown MAS as having both laboratory and clinical features.

Investigators analyzed data from 16 patients who received tocilizumab and 18 patients who did not. Of the 16 patients who received tocilizumab, 12 were diagnosed with MAS. Among the 12, researchers diagnosed 2 with full-blown MAS and the remaining 10 with possible MAS. Among the 18 tocilizumab-naive patients with MAS, 10 were diagnosed with full-blown MAS and 8 with possible MAS.

Researchers observed no significant differences between the groups with respect to age and sex; however, at the time of MAS onset, compared with the tocilizumab-untreated group, the tocilizumab-treated group was significantly less likely to develop a fever (possible MAS, P <.05 and full-blown MAS, P <.01). Among patients with MAS, the tocilizumab-treated vs the tocilizumab-untreated group had significantly lower serum ferritin levels (664 ng/mL vs 9235 ng/mL; P <.001), serum triglyceride levels (113 mg/dL vs 214 mg/dL; P <.05), and C-reactive protein levels (0.03 mg/dL vs 7.6 mg/dL; P <.0001).

Overall, compared with patients in the tocilizumab-untreated group, patients in the tocilizumab-treated group were less likely to be classified with MAS according to the ACR/EULAR MAS classification criteria (83.3% vs 25.0%; P <.01). Investigators attributed the significant difference in classification rates to the absence of fever and insufficiently elevated ferritin levels among patients treated with tocilizumab.

According to the researchers, these data suggest that tocilizumab may modify certain clinical features of MAS, including fever and serum biomarker levels; typical MAS classification criteria may be insufficient for diagnosing MAS in patients receiving tocilizumab.

Limitations included the small sample size and retrospective design of the study, and the fact that the study was insufficiently powered to conduct statistical comparisons of tocilizumab-treated and -untreated patients with full-blown MAS. Further study in a larger cohort may be necessary to expand on these findings.

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“When evaluating patients [with systemic JIA] while receiving [tocilizumab], it is not applicable to use 2016 [systemic JIA]-associated MAS criteria for these group of patients. Care must be taken to not underdiagnose MAS based on the MAS classification criteria,” the investigators concluded.

Disclosure: The institution at which this study was conducted received research grants from the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Shimizu M, Mizuta M, Okamoto N, et al. Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2020;18(1):2.