Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: Report of forty-six patients from an international multicenter series

Peter A. Nigrovic, Melissa Mannion, Femke H M Prince, Andrew Zeft, C. Egla Rabinovich, Marion A J Van Rossum, Elisabetta Cortis, Manuela Pardeo, Paivi M. Miettunen, Ginger Janow, James Birmingham, Aaron Eggebeen, Erin Janssen, Andrew I. Shulman, Mary Beth Son, Sandy Hong, Karla Jones, Norman T. Ilowite, Randy Q. Cron, Gloria C. Higgins

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Abstract

Objective To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Methods Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Results Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Conclusion Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

Original languageEnglish
Pages (from-to)545-555
Number of pages11
JournalArthritis and Rheumatism
Volume63
Issue number2
DOIs
Publication statusPublished - Feb 2011

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Interleukin 1 Receptor Antagonist Protein
Juvenile Arthritis
Therapeutics
Antirheumatic Agents
Arthritis
Tachyphylaxis
Interleukin-1 Receptors
Ferritins
Exanthema
Interleukin-1
Age of Onset
Bacterial Infections
C-Reactive Protein
Hepatitis
Medical Records
Adrenal Cortex Hormones
Fever

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Nigrovic, P. A., Mannion, M., Prince, F. H. M., Zeft, A., Rabinovich, C. E., Van Rossum, M. A. J., ... Higgins, G. C. (2011). Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: Report of forty-six patients from an international multicenter series. Arthritis and Rheumatism, 63(2), 545-555. https://doi.org/10.1002/art.30128

Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis : Report of forty-six patients from an international multicenter series. / Nigrovic, Peter A.; Mannion, Melissa; Prince, Femke H M; Zeft, Andrew; Rabinovich, C. Egla; Van Rossum, Marion A J; Cortis, Elisabetta; Pardeo, Manuela; Miettunen, Paivi M.; Janow, Ginger; Birmingham, James; Eggebeen, Aaron; Janssen, Erin; Shulman, Andrew I.; Son, Mary Beth; Hong, Sandy; Jones, Karla; Ilowite, Norman T.; Cron, Randy Q.; Higgins, Gloria C.

In: Arthritis and Rheumatism, Vol. 63, No. 2, 02.2011, p. 545-555.

Research output: Contribution to journalArticle

Nigrovic, PA, Mannion, M, Prince, FHM, Zeft, A, Rabinovich, CE, Van Rossum, MAJ, Cortis, E, Pardeo, M, Miettunen, PM, Janow, G, Birmingham, J, Eggebeen, A, Janssen, E, Shulman, AI, Son, MB, Hong, S, Jones, K, Ilowite, NT, Cron, RQ & Higgins, GC 2011, 'Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: Report of forty-six patients from an international multicenter series', Arthritis and Rheumatism, vol. 63, no. 2, pp. 545-555. https://doi.org/10.1002/art.30128
Nigrovic, Peter A. ; Mannion, Melissa ; Prince, Femke H M ; Zeft, Andrew ; Rabinovich, C. Egla ; Van Rossum, Marion A J ; Cortis, Elisabetta ; Pardeo, Manuela ; Miettunen, Paivi M. ; Janow, Ginger ; Birmingham, James ; Eggebeen, Aaron ; Janssen, Erin ; Shulman, Andrew I. ; Son, Mary Beth ; Hong, Sandy ; Jones, Karla ; Ilowite, Norman T. ; Cron, Randy Q. ; Higgins, Gloria C. / Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis : Report of forty-six patients from an international multicenter series. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 2. pp. 545-555.
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abstract = "Objective To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Methods Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Results Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22{\%}), while 67{\%} received corticosteroids and 33{\%} received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95{\%} of patients, while C-reactive protein and ferritin normalized within this interval in >80{\%} of patients. Active arthritis persisted at 1 month in 39{\%} of patients, at 3 months in 27{\%}, and at >6 months of followup in 11{\%}. Approximately 60{\%} of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Conclusion Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90{\%} of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.",
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T1 - Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis

T2 - Report of forty-six patients from an international multicenter series

AU - Nigrovic, Peter A.

AU - Mannion, Melissa

AU - Prince, Femke H M

AU - Zeft, Andrew

AU - Rabinovich, C. Egla

AU - Van Rossum, Marion A J

AU - Cortis, Elisabetta

AU - Pardeo, Manuela

AU - Miettunen, Paivi M.

AU - Janow, Ginger

AU - Birmingham, James

AU - Eggebeen, Aaron

AU - Janssen, Erin

AU - Shulman, Andrew I.

AU - Son, Mary Beth

AU - Hong, Sandy

AU - Jones, Karla

AU - Ilowite, Norman T.

AU - Cron, Randy Q.

AU - Higgins, Gloria C.

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N2 - Objective To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Methods Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Results Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Conclusion Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

AB - Objective To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Methods Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Results Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Conclusion Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

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