A Gotte

D Blankenship

F Allantaz

M Punaro

M Stoll

V Pascual

Z Xu

Pediatric Rheumatology

PubMed

Springer - Publisher Connector

PReS-FINAL-2178: Clinical and microarray follow-up of SJIA patients treated with anakinra over the past 10 years in a single institution

ORAL PRESENTATION Open Access
PReS-FINAL-2178: Clinical and microarray follow-up
of SJIA patients treated with anakinra over the
past 10 years in a single institution
M Punaro1*, A Gotte1, M Stoll1, D Blankenship2, F Allantaz3, Z Xu3, V Pascual3
From 20th Pediatric Rheumatology European Society (PReS) Congress
Ljubljana, Slovenia. 25-29 September 2013
Introduction
The role of IL-1 in the pathogenesis of SJIA was first
reported by our group in 2005.
Objectives
To evaluate the response to IL-1 blockade over the past
10 years in sJIA patients treated with anakinra at the
clinical level including the durability of response, long
term complications, and steroid sparing effect as well as
to utilize blood gene expression profiling for insight into
potential mechanisms of pathogenesis.
Methods
Clinical/laboratory data of all children with sJIA at our
institution treated with anakinra with at least 6 months
of follow-up were reviewed. Whole blood gene expression
profiling (Illumina bead chip array) was obtained in most
patients before and after initiation of IL-1 blockade and
repeated over the course of follow-up.
Results
51 SOJIA patients (30 F/21 M) with median disease
duration of 1.0 years (range 0 days post dx-11.6 years)
and median of 4 active joints (range 0-40) at initiation
of anakinra were treated with a mean dose of 2.67 mg/kg
(range 1-10) with an average follow-up of almost 5 years
(range 0.49-9.75) on anakinra. All children had a sJIA
signature as previously described (1) by microarray
analysis.
After 1L-1 blockade, significant improvements were
seen in rash (p = 0.0008), fever (p < 0.0001), number
of active joints (p = 0.0002), WBC (p < 0.0001),
hemoglobin (p < 0.0001), platelets (p < 0.00001), and
ESR (p < 0.0001).
Twenty-two patients (17 new, 5 with flares) were treated
without any steroids on anakinra alone (18), or concomi-
tantly with methotrexate (4).
37/51 (72%) patients met Wallace criteria for inactive
disease, 30/51 (59%) for clinical remission on medica-
tions, and 13/51 (25%) met criteria for clinical remis-
sion. Eight children (16%) had a partial response with
important clinical improvements and were able to stop
or greatly wean steroids. Five children (10%) had no
sustained response.
Most side effects were minor although 1 patient had
sepsis immediately after IVMP. One patient had a drug
induced hepatitis necessitating discontinuation of
anakinra. One patient continued anakinra throughout
pregnancy and delivered a normal term baby. Four
patients with clinical MAS have resolved on anakinra.
Gene expression profiling showed a remarkably homo-
geneous pattern of IL-1 related gene dysregulation (1),
which normalized in most patients after anakinra. In
some patients there was a time lapse between clinical
response and correction of gene expression, suggesting
that immune alterations are not completely resolved
at time of first clinical response. Most upregulated
transcripts encoded innate immunity related proteins.
Down regulated transcripts encoded proteins involve in
cytoxic/NK cell function and protein synthesis. In a
small number of patients, interferon inducible genes
were upregulated, especially in patient who had never
received steroids and 5/7 of these showed normalization
post anakinra.
1Arthritis, Texas Scottish Rite Hospital for Children, Dallas, TX, USA
Full list of author information is available at the end of the article
Punaro et al. Pediatric Rheumatology 2013, 11(Suppl 2):O13
http://www.ped-rheum.com/content/11/S2/O13
© 2013 Punaro et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Conclusion
Anakinra is safe and effective in controlling clinical
disease and correcting gene expression alterations in
most children with sJIA in long term follow up. When
used early in the disease course, most patients can be
managed without corticosteroids, historically a major
cause of morbidity in these patients.
Disclosure of interest
None declared.
Authors’ details
1Arthritis, Texas Scottish Rite Hospital for Children, Dallas, TX, USA. 2Arthritis,
Baylor Institute of Immunology Research, Dallas, TX, USA. 3Research, Baylor
Institute of Immunology Research, Dallas, TX, USA.
Published: 5 December 2013
doi:10.1186/1546-0096-11-S2-O13
Cite this article as: Punaro et al.: PReS-FINAL-2178: Clinical and
microarray follow-up of SJIA patients treated with anakinra over the
past 10 years in a single institution. Pediatric Rheumatology 2013
11(Suppl 2):O13.
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Punaro et al. Pediatric Rheumatology 2013, 11(Suppl 2):O13
http://www.ped-rheum.com/content/11/S2/O13
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PReS-FINAL-2178: Clinical and microarray follow-up of SJIA patients treated with anakinra over the past 10 years in a single institution

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