Rather than waiting for other drugs
or immunotherapies to fail, an immediate up-front but time-limited
course of an interleukin- 1 receptor
(IL-1R) antagonist induced rapid
and sustained remissions in most
children with systemic juvenile idiopathic arthritis (JIA), according to
5-year data presented at the Congress.
In the latest follow-up of a protocol first described in 2014, over
90% of patients still had inactive
disease, 75% of whom were completely off therapy, reported Dr.
Sebastiaan J. Vastert of the division
of pediatrics at University Medical
Centre, Utrecht (Netherlands).
The proportion of sustained re-
sponses with a limited course of
upfront anti–IL-1R is greater than
that reported for this or other bi-
ologics when used second line,
Citing a series of experimental
studies at his institution that sug-
gest immune mediators change as
systemic JIA evolves from an acute
to a chronic phase, Dr. Vastert be-
lieves that early use of an anti–IL-
1R therapy may alter the trajectory
of systemic JIA, compared with
when it goes untreated or is treat-
ed with conventional therapies.
In the original series reported
in 2014 (Arthritis Rheumatol. 2014
Apr;66:1034-43), data were presented on 20 patients. All fulfilled
the International League of Associations for Rheumatology criteria
for systemic JIA. They were treated
with anakinra after failing to respond to indomethacin but before
receiving any other therapy, including glucocorticoids, disease-modifying antirheumatic drugs, or other
In the protocol described in the
initial publication, a stop-therapy
strategy permitted treatment discontinuation after 3 months in
those who met American College
of Rheumatology criteria for 90%
improvement (ACR Pedi 90) in JIA.
By 1 year, 73% of the patients
had met criteria to stop therapy. Of
11 patients followed for 3 years, 10
met criteria for disease remission, 8
of whom were off medication. The
remaining two continued to receive
anti–IL-1R or another therapy.
The systemic JIA cohort at Dr.
Vastert’s institution has now grown
to 50 patients, of whom 42 patients
have received first-line anakinra.
Among the 25 patients who have
been followed for at least 5 years,
72% have inactive disease, as de-
fined by ACR Pedi 90 criteria off
therapy. Another 20% have inactive
disease on therapy, which is anak-
inra or another biologic in most
cases. The majority of patients have
avoided glucocorticoids completely.
Freedom from glucocorticoids
has been accompanied by high
rates of satisfaction and has al-
lowed patients to avoid adverse
events associated with glucocor-
ticoids. For example, only one
patient in this series has a growth
curve more than two standard de-
viations below normal for age and
gender, according to Dr. Vastert.
“This is just a single-centre co-
hort study, but we now have 3
more years of data to be convinced
of this concept,” Dr. Vastert said.
Another notable finding from
this cohort: 12 patients have been
enrolled who did not fulfill International League of Associations
for Rheumatology criteria for systemic JIA because of the absence
of joint involvement. Strongly
suspected of having systemic JIA
because of other clinical signs and
features, these patients have also
responded well to first-line anakinra therapy.
“Our data point to a classification [of systemic JIA] that does not
include arthritis as a prerequisite
for diagnosis,” said Dr. Vastert,
who provided data suggesting that
elevated levels of IL- 18 might be
among biomarkers that could be
employed in a revised classification system.
The study was not funded by in-
dustry. Dr. Vastert reported receiv-
ing consulting fees from Novartis. Dr. Sebastiaan J. Vastert
Limited anakinra course often enough for
systemic JIA, if used first
BY TED BOSWORTH