open access: Nature Reviews: Key Advances in Medicine

RHEUMATOLOGY
JIA. 6 They represent the first official treatment
recommendations for JIA to be based
on objective, validated methods, and have
already been reviewed in this journal. 7 The
term ‘recommendations’ was used, instead of
‘guidelines’, to emphasize their nonprescriptive
nature; the intended aim of the publication
was to support, but not to dictate,
the individual physician’s decision. The
recommendations are based on a comprehensive
list of clinical scenarios, in which
hypothetical patients are categorized on the
basis of different combinations of key clinical
parameters rele vant to the decision-making
process, such as disease activity and potential
prognostic features.
The ACR recommendations are a very
useful tool, which can guide the treatment of
patients with JIA, but will soon require updating
given the rapid evolution of this field.
Indeed, tocilizumab—an antibody against
the IL-6 receptor that has now been approved
for the treatment of systemic JIA by both the
FDA and the EMA—is not considered in
the recommendations. More over, trials are
currently being performed in patients with
systemic JIA that aim to investigate the efficacy
of two IL-1 inhibitors, canakinumab (a
monoclonal anti-IL-1 antibody) and rilonacept
(the recombinant extracellular domain of
the human IL-1 receptor); the results of these
studies will soon be available, and will presumably
provide important new information
re garding treatment of this disease.
Although the introduction of biologic
therapies has represented a major advance
in the treatment of JIA, the fact remains
that the high costs associated with provision
of these agents can be afforded only by
the health care systems of a limited number
of countries. 8 Around the world, most children
with JIA have to rely on much less
expensive drugs, such as methotrexate.
Therefore, data regarding the efficacy of
combination therapies comprising methotrexate
and other synthetic DMARDs in
compari son with metho trexate alone would
be viewed with interest by rheuma tologists
worldwide. However, in contrast to rheumatoid
arthritis—a dis ease in which many trials
have supported the over all superiority of
combination DMARD therapy over methotrexate
monotherapy 9 —data on combi nation
DMARD therapy are lacking for JIA.
Important findings supporting the potential
efficacy of combination DMARD therapy
in JIA were presented last year by Tynjälä
et al. 10 The authors randomly assigned 59
patients with early poly articular JIA to
three treatment cohorts: infliximab plus
methotrexate; methotrexate alone; or methotrexate,
sulfa salazine and hydroxychloroquine
in combination. The results of this
trial showed that infliximab plus methotrexate
was su perior to combination therapy and
strikingly superior to methotrexate alone. An
interest ing aspect of this study was, therefore,
that synthetic DMARDs in combi nation
seemed to be superior to metho trexate
treatment alone, although the difference
in effi cacy was not statistically significant.
The study was, however, underpowered to
show a signifi cant difference and the trend
in favor of combination therapy was consistent
for all the endpoints tested. Thus, these
results strongly suggest that combination
therapies with inexpensive synthetic drugs
could prove superior to methotrexate alone
in future studies with appropriate sample
sizes. The funding of these potentially very
relevant investigator-initiated randomized
studies should represent a future priority for
in ternational public funding bodies.
2011 has witnessed important new advances
in the understanding and manage ment of JIA,
but much remains to be done. In the future,
more accurate classification of patients with
JIA will be possible and more effec tive treatments
will become avail able, owing to the
integration of clinical data with the results of
research into dis ease pathogenesis.
University of Genoa, Pediatria II e
Reumatologia, Istituto G. Gaslini, Largo G.
Gaslini 5, 16147 Genoa, Italy.
albertomartini@ospedale-gaslini.ge.it
Competing interests
The author declares no competing interests.
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or the presence of psoriasis still useful tools
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SLE IN 2011
Deciphering the role of NETs
and networks in SLE
Thomas Dörner
From neutrophil extracellular traps to genetic networks that underlie the
disease and new targeted therapies, important advances in 2011 improve
our understanding of the pathogenesis of systemic lupus erythematosus
and mark the beginning of our ability to treat it effectively.
Dörner, T. Nat. Rev. Rheumatol. 8, 68–70 (2012); published online 10 January 2012;
doi:10.1038/nrrheum.2011.200
2011 was a year of achievements in systemic
lupus erythematosus (SLE)—for advances
in basic and clinical research, and the translation
of these findings into daily clinical
practice. After a decade of failures of some
biologic therapies in SLE, the recog nition of
particular cellular and cytokine pathways as
involved in the pathogenesis has initiated a
promising period of progress in this complex
disease. Many excellent contributions were
published in 2011, but a few studies deserve
emphasis for providing new perspectives.
S68 | JANUARY 2012 www.nature.com/reviews