Anakinra for systemic juvenile arthritis: the Rocky Mountain experience.
BACKGROUND
Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements.


OBJECTIVE
To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients.


METHODS
We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment.


RESULTS
Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site.


CONCLUSIONS
Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.
Division of Immunology and Rheumatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah 84158, USA. andrew.zeft@hsc.utah.edu
Andrew
A
Zeft
Roger
R
Hollister
Bonnie
B
LaFleur
Prahalad
P
Sampath
Jennifer
J
Soep
Bernadette
B
McNally
Gary
G
Kunkel
Margaret
M
Schlesinger
John
J
Bohnsack
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy*; D001799:Blood Sedimentation; D002648:Child; D002675:Child, Preschool; D003120:Colorado; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009009:Montana; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D016896:Treatment Outcome; D014589:Utah
D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1