Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Canakinumab

Alexei A. Grom, Norman Todd Ilowite, Virginia Pascual, Hermine I. Brunner, Alberto Martini, Daniel Lovell, Nicolino Ruperto, Karolynn Leon, Karine Lheritier, Ken Abrams

Research output: Contribution to journalArticle

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Abstract

Objective In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS," "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years. Results Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.

Original languageEnglish (US)
Pages (from-to)218-228
Number of pages11
JournalArthritis and Rheumatology
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2016

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Macrophage Activation Syndrome
Juvenile Arthritis
canakinumab
Placebos
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology

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Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Canakinumab. / Grom, Alexei A.; Ilowite, Norman Todd; Pascual, Virginia; Brunner, Hermine I.; Martini, Alberto; Lovell, Daniel; Ruperto, Nicolino; Leon, Karolynn; Lheritier, Karine; Abrams, Ken.

In: Arthritis and Rheumatology, Vol. 68, No. 1, 01.01.2016, p. 218-228.

Research output: Contribution to journalArticle

Grom, AA, Ilowite, NT, Pascual, V, Brunner, HI, Martini, A, Lovell, D, Ruperto, N, Leon, K, Lheritier, K & Abrams, K 2016, 'Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Canakinumab', Arthritis and Rheumatology, vol. 68, no. 1, pp. 218-228. https://doi.org/10.1002/art.39407
Grom, Alexei A. ; Ilowite, Norman Todd ; Pascual, Virginia ; Brunner, Hermine I. ; Martini, Alberto ; Lovell, Daniel ; Ruperto, Nicolino ; Leon, Karolynn ; Lheritier, Karine ; Abrams, Ken. / Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Canakinumab. In: Arthritis and Rheumatology. 2016 ; Vol. 68, No. 1. pp. 218-228.
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abstract = "Objective In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as {"}probable MAS,{"} {"}possible MAS,{"} or {"}MAS unlikely,{"} using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years. Results Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95{\%} confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.",
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T1 - Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Canakinumab

AU - Grom, Alexei A.

AU - Ilowite, Norman Todd

AU - Pascual, Virginia

AU - Brunner, Hermine I.

AU - Martini, Alberto

AU - Lovell, Daniel

AU - Ruperto, Nicolino

AU - Leon, Karolynn

AU - Lheritier, Karine

AU - Abrams, Ken

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objective In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS," "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years. Results Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.

AB - Objective In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS," "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years. Results Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.

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