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Secukinumab cut ankylosing spondylitis symptoms in
MEASURE trials
BY NICOLA GARRETT
Frontline Medical News
From the New England
Journal of Medicine
S
ecukinumab, an interleukin
17-A inhibitor approved for the
treatment of moderate to severe
psoriasis, significantly reduced the
signs and symptoms of ankylosing
spondylitis in two phase III trials,
researchers reported Dec. 23 in the
New England Journal of Medicine
.
The results of the double-blind
MEASURE 1 and MEASURE 2
trials extend the positive results
of the phase II study, according
to Dr Dominique Baeten of the
Academic Medical Centre at the
University of Amsterdam and his
colleagues (
N Engl J Med
2015 Dec
23. doi: 10.1056/NEJMoa1505066).
“Although head-to-head trials
would be required to fully assess
the efficacy and safety of secuki-
numab versus TNF-inhibitors, the
[20% improvement in Assessment
of Spondyloarthritis International
Society (ASAS20) response crite-
ria] response rates achieved with
secukinumab at week 16 in our
studies were similar to those re-
ported in phase III studies of anti-
TNF agents in which most of the
patients had not received previous
anti-TNF therapy (response rates of
58% to 64% at weeks 12 to 24), even
though 30% to 40% of the patients in
our studies had had no response to
previous anti-TNF treatment,” the
authors wrote.
“Thus, secukinumab not only is
effective in patients who have not
received TNF agents previously but
also may be effective in patients in
whom previous anti-TNF treatment
failed,” they added.
In MEASURE 1, 371 patients
received intravenous secukinumab
(10 mg/kg of body weight) or
matched placebo at weeks 0, 2,
and 4, followed by subcutaneous
secukinumab (150 mg or 75 mg)
or matched placebo every 4 weeks
starting at week 8.
The study’s primary endpoint of
ASAS20 response rates at week 16
were 61%, 60%, and 29% for sub-
cutaneous secukinumab at doses of
150 mg and 75 mg and for placebo,
respectively, (P < 0.001 for both
comparisons with placebo).
In MEASURE 2, 219 patients re-
ceived subcutaneous secukinumab
(150 mg or 75 mg) or matched
placebo at baseline; at weeks 1, 2,
and 3; and every 4 weeks starting
at week 4.
At week 16, patients in the place-
bo group were randomly reassigned
to subcutaneous secukinumab at a
dose of 150 mg or 75 mg.
In this trial, ASAS20 rates were
61%, 41%, and 28% for subcutaneous
secukinumab at doses of 150 mg and
75 mg and for placebo, respectively
(P < 0.001 for the 150-mg dose and
P = 0.10 for the 75-mg dose).
The researchers noted that the
ineffectiveness of the 75-mg dose
in MEASURE 2 suggests that the
efficacy of secukinumab at the 75-
mg dose in MEASURE 1 may have
been due to the greater exposure at
week 16 as a result of the intravenous
loading regimen, not to the 75-mg
subcutaneous maintenance dose.
The safety profile of secukinumab
in the present studies was consistent
with previous studies of secukinum-
ab for ankylosing spondylitis and
moderate-to-severe plaque psoriasis,
Dr Baeten and his associates said.
During the entire treatment period,
pooled exposure-adjusted incidence
rates of grade 3 or 4 neutropenia,
candida infections, and Crohn’s
disease were 0.7, 0.9, and 0.7 cases
per 100 patient-years, respectively, in
secukinumab-treated patients.
Overall, the results suggest that
interleukin-17A plays a role in the
pathogenesis of ankylosing spondy-
litis, and they validate inhibition of
this cytokine as a potential thera-
peutic approach, the study authors
concluded.
The study was sponsored by Novartis
Pharma. Dr Baeten has received a
grant fromNovartis to study the impact
of IL-17A blockade in experimental
models of spondyloarthritis. He also
has been a consultant for Novartis
for the design and conduct of the
secukinumab program in ankylosing
spondylitis and psoriatic arthritis.
Wearable device offers home-
based knee OA pain relief
BY PATRICE WENDLING
Frontline Medical News
From Rheumatology
A
wearable pulsed electromagnetic
fields device reduced pain inten-
sity and improved physical func-
tioning in patients with painful knee
osteoarthritis (OA) in a double-blind,
randomised trial.
The commercially available device
(ActiPatch, Bioelectronics Corp.) did
not improve patients’ mental health,
but significantly reduced patients’
intake of NSAIDs and analgesics,
compared with placebo.
“Although NSAIDs remain the
gold standard for the treatment of
pain in OA, there is increasing need
to find conservative and alternative ap-
proaches, in order to avoid the toxicity
associated with the chronic use of the
analgesics, mostly in the elderly popu-
lation,” wrote Dr Gian Luca Bagnato
of the University of Messina (Italy)
and his colleagues.
Pulsed electromagnetic fields
(PEMF) therapy has been shown to
reduce chondrocyte apoptosis and
MMP-13 expression of knee cartilage
and favourably affect cartilage ho-
meostasis in animal models, but data
regarding osteoarthritis (OA) pain and
function in humans are mixed.
A recent systematic review found
no effect in all 14 trials analysed, but
when only high-quality randomised
clinical trials were included, PEMF
provided significantly better pain relief
at 4 and 8 weeks and better function at
8 weeks than did placebo (
Rheumatol-
ogy
2013;52:815–24).
Not only has the quality of trials var-
ied, so has the PEMF pulse frequency
and duration used in trials, “further
limiting the possibility of comparing
efficacy and safety,” Dr Bagnato and
associates observed.
The current study evenly ran-
domised 60 patients with radiologic
evidence of knee OA and persistent
pain to wear the PEMF or a placebo
device for a minimum of 12 hours,
mainly at night, with the device kept
in place with a wrap. The active device
emits a form of non-ionising electro-
magnetic radiation at a frequency of
27.12 MHz, a pulse rate of 1,000 Hz,
and a burst width of 100 microsec.
Persistent pain was defined as a
minimal mean score of 40 mm for
global pain on the VAS (visual analog
scale) and daily pain during the month
prior to enrollment despite maximal
tolerated doses of conventional medi-
cal therapy, including acetaminophen
and/or an NSAID. The patients’ mean
age was 67.7 years and mean OA dura-
tion 12 years.
The primary efficacy endpoint was
reduction in pain intensity at 1 month
on the VAS and WOMAC (Western
Ontario and McMaster Universities
Arthritis Index). The mean WOMAC
total score at baseline was 132.9.
At 1 month, VAS pain scores were
reduced 25.5% with the PEMF device
and 3.6% with the placebo device.
The standardised treatment effect
size induced by PEMF therapy was
–0.73 (95% confidence interval, –1.24
to –0.19), the investigators reported.
WOMAC pain subscale and total
scores fell 23.4% and 18.4% with the
PEMF device versus a 2.3% reduc-
tion for both scores with the placebo
device. The standardised effect size
was –0.61 for WOMAC pain (95%
CI, –1.12 to –0.09) and –0.34 for
WOMAC total score (95% CI, –0.85
to 0.17).
At 1month, the mean Short Form-36
physical health score was significantly
better in the PEMF group than in the
placebo group (55.8 vs 53.1; P = 0.024),
while SF-36 mental health scores were
nearly identical (43.8 vs 43.6; P = 0.6).
Patients were allowed per protocol
to take prescribed analgesic therapy
as needed, but eight patients from the
PEMF group stopped these medica-
tions, while one patient from the pla-
cebo group stopped medication and
three started a new therapy for chronic
pain. No adverse events were reported
during the study.
“Given that our data are limited to
a low number of participants and the
long-term efficacy of the wearable de-
vice is unknown, the generalisability of
the results needs to be confirmed in a
larger clinical trial with a longer dura-
tion of treatment,” Dr Bagnato and
his coauthors concluded. “However,
the use of a wearable PEMF therapy
in knee OA can be considered as an
alternative safe and effective therapy
in knee OA, providing the possibility
for home-based management of pain,
compared with previous studies.”
US FDA
announces
new plan
to combat
opioid abuse
BY ALICIA GALLEGOS
Frontline Medical News
US
Food and Drug Administra-
tion officials are calling for a
sweeping overhaul of the agency’s
approach to opioid medications, in-
cluding renewed efforts to improve
how opioids are approved, labelled,
and prescribed.
The initiative focuses on new
policies to help reverse the opioid
abuse epidemic, while still provid-
ing patients in pain with access to
effective relief, Dr Robert M. Califf,
FDA deputy commissioner for medi-
cal products and tobacco, said in a
Feb. 4 announcement.
“Things are getting worse, not
better, with the epidemic of opioid
misuse, abuse and dependence,”
said Dr Califf, who has been nomi-
nated but not confirmed as FDA
commissioner. “It’s time we all took
a step back to look at what is work-
ing and what we need to change to
impact this crisis.”
Under the new plan, the FDA will
convene an advisory committee be-
fore approving new drug applications
for opioids that do not have abuse-
deterrent properties and develop
changes to immediate-release opioid
labeling. The agency also plans to
expand access to abuse-deterrent
formulations of opioid products and
improve the availability of naloxone
and medication-assisted treatment
options for patients with opioid use
disorders.
In a Feb. 4 editorial published
in the
New England Journal of
Medicine
, Dr Califf noted that
the number of annual deaths from
opioid overdoses now exceeds the
number of annual deaths from mo-
tor vehicle accidents (doi:10.1056/
NEJMsr1601307).
“Regardless of whether we view
these issues from the perspective
of patients, physicians, or regula-
tors, the status quo is clearly not
acceptable,” Dr Califf wrote in
the editorial. “As the public health
agency responsible for oversight of
pharmaceutical safety and effective-
ness, we recognise that this crisis
demands solutions. We are commit-
ted to action, and we urge others to
join us.”
Regardless of whether we
view these issues from the
perspective of patients,
physicians, or regulators,
the status quo is clearly not
acceptable.
Secukinumab not only is effective in patients who have not
received TNF agents previously but also may be effective in
patients in whom previous anti-TNF treatment failed.
Courtesy BioElectronics Corporation
R
heumatology
N
ews
• Vol. 4 • No. 1 • 2016
NEWS
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