Background/Purpose:
Macrophage activation syndrome (MAS),
a potentially fatal complication of systemic juvenile idiopathic arthritis
(SJIA), was reported as an adverse event in both canakinumab and placebo group
patients in Phase III trials.¹ This prompted the formation of an independent
expert MAS Adjudication Committee (MASAC), to develop a methodology to identify
and adjudicate potential MAS events. Here, we report frequency of MAS as
adjudicated by the MASAC, in canakinumab-naïve SJIA patients² from
the Phase III, trial program.  

Methods: Potential MAS events were identified by periodic
searches of the canakinumab SJIA clinical study safety and lab databases for
MASAC-specified screening AE terms and lab criteria. MAS events were then
adjudicated blinded to treatment by the MASAC as either probable, possible, or
unlikely MAS, or insufficient information loosely based on the diagnostic
criteria by Ravelli et al.³

Results: MASAC identified 72 potential cases for
adjudication. Twenty one events in 19 patients were adjudicated as Probable MAS
and 10 events in 9 patients as Possible MAS. Of the 21 Probable MAS events, 19
occurred in the canakinumab and 2 in the placebo group. The time period between
the first injection of canakinumab and the onset of MAS ranged between 3 to 1359
days (median, 531 days). The rate for MASAC adjudicated Probable MAS was 2.8/100
patient-years and 7.7/100 patient-years for the canakinumab and placebo groups
(Table), respectively with no statistically significant difference between
groups (diff=-4.9, 95% CI, -15.6, 5.9). Three patients (canakinumab, n=2;
placebo, n=1) died due to complications of MAS and full recovery was reported
in the remaining patients.

Table. Exposure adjusted incidence rate of events adjudicated as
Probable MAS

*Clinical program included studies: Phase II; Phase
III Trial 1; Phase III Trial 2; Phase III Trial 2

extension; MAS = macrophage activation syndrome; MASAC
= MAS Adjudication Committee

Conclusion: Canakinumab does not appear to have an effect on the
frequency of macrophage activation syndrome or modify its clinical features.

Reference:

1.    
Ruperto et al. N Engl J
Med. 2012;367:2396-406.

2.    
Ruperto et al. Ann Rheum
Dis. 2015;74(2):608.

3.    
Ravelli A, et al. J
Pediatr. 2005;146(5):598-604.