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Arthritis & Rheumatism
In thisIssue
Highlights from this issue of A&R | BY SUE PONDROM
Canakinumab Provides
Pain Relief for Patients
with Gouty Arthritis
Canakinumab, a fully human anti-interleukin–1β monoclonal antibody, provided
rapid and sustained pain relief in patients
with acute gouty arthritis and significantly
reduced the risk of recurrent flares compared with triamcinolone acetonide,
according to So et al (p. 3064).
Because patients
with gout with multiple comorbidities may
not tolerate or find effective relief with
nonsteroidal antiinflammatory drugs or
colchicine, the authors sought another
treatment option. In an 8-week, singleblind, double-dummy, dose-ranging study,
patients were randomized to receive a
single subcutaneous dose of canakinumab
or an intramuscular dose of triamcinolone. The canakinumab was generally
well tolerated with no organ toxicity
being observed and no specific doserelated effects. The 4 adverse events
reported were not considered to be
related to the study medication. The
patients assessed their pain using a
100-mm visual analog scale.
The authors reported that 72 hours
after treatment, a statistically significant
dose response was observed for
canakinumab and all canakinumab doses
were associated with less pain than triamcinolone acetonide. A 150 mg dose of
canakinumab demonstrated consistently
superior efficacy to 40 mg of triamcinolone acetonide across all assessments,
including a clinically meaningful difference
in pain reduction by 24 hours, time to
50% pain reduction, patient’s and physician’s global assessments, reductions in
markers of inflammation, rescue medication use, and risk of recurrent flares.
p. 3064
DMARDs, Glucocorticoids, and Biologic
Agents Have Similar Effects in RA
In a meta-analysis of 70 clinical trials involving
patients with rheumatoid arthritis (RA),
Graudal and Jürgens (p. 2852) have shown that
treatments with single and
combination disease-modifying antirheumatic drugs
(DMARDs), glucocorticoids, and biologic
agents were similar in significantly reducing
radiographic progression at 1 year, with a relative effect of 48–84%.
The authors’ meta-analysis looked at randomized trials that investigated the effects of
drug treatment on the percentage of the annual
radiographic progression rate (PARPR) in RA.
They noted that compared with placebo, the
PARPR was 0.65% smaller in the singleDMARD group and 0.54% smaller in the
glucocorticoid group. Compared with singleDMARD treatment, the PARPR was 0.62%
smaller in the combination-DMARD group
p. 2852
and 0.61% smaller in the biologic agent plus
methotrexate (MTX) group. The effect of a
combination of 2 DMARDs plus step-down
glucocorticoids did not differ from the effect
of a biologic agent plus MTX.
The authors said their findings remove
any previous doubt that may have existed
about the efficacy of single-DMARD treatment on radiographic progression in RA.
According to the team, their meta-analysis
“confirms that aggressive treatment with
combination DMARD does reduce structural
joint damage as compared with less-aggressive treatment with a single DMARD and
that combination-DMARD treatment, especially when combined with periodic glucocorticoids, may be as effective as a biologic
agent plus MTX.” They recommend that
treatment with a DMARD continue to be the
first choice for RA.
Adiponectin Involved in RA Pathophysiology
Frommer et al (p. 2886) have analyzed how
adipokine adiponectin, a C1q/tumor necrosis
factor α homolog, is increased in the synovial
fluid of rheumatoid arthritis (RA) patients compared with osteoarthritis (OA) patients.
By investigating the differential effects that
adiponectin might have within the RAjoint, the
authors found adiponectin present at sites of
cartilage invasion and in inflamed synovium,
lymphocyte infiltrates, and perivascular areas.
They determined that adiponectin induces gene
expression and protein synthesis in human RA synovial fibroblasts (RASFs),
lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin
p. 2886
Figure 1. Induction of Interleukin-6 (IL-6), RANTES, and MMP-3 mRNA expression in bovine chondrocytes
by adiponectin.
being involved in the pathophysiologic modulation of RA effector cells.
Using OASFs, which do not display an
activated phenotype, the team determined
that RASFs exhibited a stronger response to
adiponectin than did OASFs. “Therefore,
adiponectin probably plays a more significant
role in RA than in OA, especially with regard
to the chronic inflammation and the aggressive
phenotype of RASFs,” they said.
The authors observed that adiponectin stimulated the synthesis of chemokines in particular,
but also of cytokines, matrix metalloproteinases
(MMPs), genes involved in inflammation and
bone metabolism, and receptors and growth
factors in RASFs.
A21
Little Efficacy, Adverse Events Seen with Abatacept in Patients
with SLE
In a 12-month, multicenter, phase IIb, randomized, double-blind trial, defined according to the primary manifestation at study entry.
patients with non–life-threatening systemic lupus erythematosus
The study authors noted that although the findings suggest the
(SLE) and polyarthritis, discoid lesions, or pleuritis and/or peri- possibility of clinical activity of abatacept, there was an increased
carditis showed improvements in certain exploratory measures with incidence of serious adverse events, which requires further characabatacept. Merrill et al (p. 3077), however, reported that the study’s terization.
primary/secondary end points were not met.
In an e-mail to “In This Issue,” the authors said “a future study
During the trial, 118 patients were randomized might best examine flares which physicians consider to be clinically
to receive abatacept and 57 to receive placebo. significant, which is more likely to include British Isles Lupus AsPrednisone was given for 1 month and then ta- sessment Group (BILAG) A flares then BILAG B flares based on
pered. The primary end point was the proportion of patients with new data collected in this trial.”
flare (adjudicated) according to a score of
A/B on the British Isles Lupus Assessment
Group (BILAG) index after the start of the
steroid taper. The secondary end points
included the proportion of patients with a
new SLE flare within the initial 6 months,
time to new flare occurrence, the proportion of patients with no new flares while receiving steroids, and the Systemic Lupus
International Collaborating Clinics/American College of Rheumatology Damage
Index at 12 months compared to baseline.
Prespecified exploratory analyses evaluFigure 1. Health-related quality of life over 12 months in patients with SLE.
ated the primary end point in subgroups
p. 3077
Murine Model of Polymyositis Shows Cytotoxic CD8 T Cell Involvement
In the C protein–induced myositis (CIM)
murine model of polymyositis (PM), Sugihara
et al (p. 3088) have shown that perforinmediated cytotoxicity by CD8 cells is
responsible for muscle injury in the unique
mouse model.
The team immunized β2-microglobulin–
null and perforin–null mutant mice, as well
as wild-type (WT) C57BL/6 mice, with skeletal muscle C protein fragments to provoke
CIM. Regional lymph node CD8 or CD4 T
cells stimulated with C protein–pulsed
dendritic cells were transferred adoptively
to naive mice. Inflammation and damage of
the muscle tissues were evaluated
histologically.
The β2-microglobulin–null and
perforin–null mutant mice developed
myositis with lower incidence than WT mice and
less severe inflammation
and muscle injury. In addition, adoptive
transfer of lymph node T cells from mice
with CIM induced myositis in naive recipient
mice.The CD8 T cell–induced muscle injury
was significantly more severe than the
CD4 T cell–induced muscle injury.
According to the authors, the CIM
mouse model is the one most analogous
to human PM. They said their study
demonstrates that CD8 cytotoxic
T lymphocytes primarily damage the
muscle fibers in CIM.
p. 3088
Figure 1. Muscle fibers invaded by inflammatory mononuclear cells were found to be abundant in the WT mice
(A), but not in the β2-microglobulin–null mutant mice (B).
A22
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