Rheumatology News

10 / 16

First US clinical practice guidelines arise for
Sjögren’s syndrome management
BY M. ALEXANDER OTTO
Frontline Medical News
At the American College of Rheumatology
annual meeting, San Francisco
Rituximab is, for now, the first-line option
for Sjögren’s syndrome patients with
systemic symptoms severe enough to
require biologic therapy, according to new
systemic treatment guidelines from the
Sjögren’s Syndrome Foundation.
In general, tumour necrosis factor in-
hibitors are out because of the risk of lym-
phoma; Sjögren’s patients are already at risk
for the disease.
The foundation has also released guidelines
for the management of dry eyes and preven-
tion of cavities in Sjögren’s. Thirteen more
guidelines are in the works to tackle neuro-
logic complications, lung disease, lymphoma,
and other issues. The ocular guidelines have
been published; the systemic and cavity ones
will be soon.
“We are really excited about this. These
are the first US clinical practice guidelines
for Sjögren’s. It will be a game changer,” said
Katherine Hammitt, the Sjögren’s Syndrome
Foundation’s vice president of medical and
scientific affairs.
Topical fluoride should be used in all
patients with dry mouth to prevent cavi-
ties, along with measures or medications
to increase saliva. A comprehensive corneal
exam is the first step for dry eyes to deter-
mine if they’re due to a lack of tears or ab-
normal oil secretion by eyelid glands, which
causes tears to evaporate too soon. Treat-
ment proceeds according to the findings.
The recommendations are based on a
literature review and the consensus of
about 100 Sjögren’s experts. The guidelines
address what the experts considered to be
the most pressing problems.
The foundation launched the efforts after
fielding calls from patients reporting that
doctors didn’t understand the disease; didn’t
take it seriously; or said there was noth-
ing that could be done. On the flip side,
physicians were calling in about problem
patients.
“So about 5 years ago, we launched an ini-
tiative to address the issues.” With current
options, “to tell patients that they don’t need
treatment or that nothing can be done is, in
my view as a rheumatologist, malpractice,”
said presenting author Dr Frederick Vivino,
chief of rheumatology at Penn Presbyterian
Medical Centre, a University of Pennsyl-
vania teaching hospital in Philadelphia.
He is also director of the Penn Sjögren’s
Syndrome Centre.
Rituximab isn’t approved for Sjögren’s, but
“clinicians are using it quite frequently be-
cause it’s really the only [biologic] out there”
for the disease. “We’ve seen moderate im-
provement” of organ involvement, vasculitis,
neuropathy, and other extraglandular prob-
lems, but “it hasn’t knocked our socks off. We
need something better than rituximab” for
the sickest patients, Ms Hammitt said at the
annual meeting of the American College of
Rheumatology. The guidelines recommend
hydroxychloroquine as the first step for in-
flammatory musculoskeletal pain, followed,
as needed, by methotrexate, steroids, and
other options. Azathioprine is a good option
for recalcitrant musculoskeletal pain, as well
as organ involvement. Meanwhile, aerobic
exercise is important to help with fatigue.
A baseline corneal exam is “the most im-
portant recommendation” for eye patients,
Dr Vivino said.
A stepwise treatment algorithm based
on the nature and severity of the problem
comes next, and can included tear sup-
plementation and stabilisation; control of
inflammation of the lacrimal glands and
ocular surface; systemic therapy with secre-
tagogues; tear preservation measures; and
eyelid surgery. Salivary deficiency causes
cavities in Sjögren’s. “If the patient has
dry mouth, they need to be given topical
fluoride. Either encourage them to ask their
dentist, or, as I would do, just prescribe it,
and they should use it on a regular basis.
The group also felt that giving medications
to stimulate saliva flow,” like pilocarpine
or cevimeline, “would likely help prevent
caries, as well,” Dr Vivino said.
Sugar-free lozenges or chewing gum can
also help with saliva flow. The group gave
a weak recommendation for chlorhexidine
varnishes, gels, and rinses, and a moderate
one for nonfluoride remineralising agents.
The work was supported by the Sjögren’s Syn-
drome Foundation, with no pharmaceutical
industry funding. Some of the authors have
financial ties to numerous pharmaceutical
companies.
Actual-weight hydroxychloroquine dosing
works in SLE, up to a point
BY M. ALEXANDER OTTO
Frontline Medical News
At the American College of Rheumatology
annual meeting, San Francisco
Hydroxychloroquine dosing based on
actual body weight – instead of ideal
weight – is appropriate for patients
with systemic lupus erythematosus (SLE),
according to a review of 686 lupus patients
at Johns Hopkins University in Baltimore.
Most were dosed by actual weight, 6.5
mg/kg up to a maximum of 400 mg/day. Pa-
tients with renal insufficiency were dosed
at 200 mg daily, and those on haemodialysis
received 200 mg after their sessions.
In their analysis, Hopkins researchers
calculated that ideal and actual body weight
dosing yielded statistically equivalent hy-
droxychloroquine blood levels. “This was re-
assuring. The take-home message is dosing
based on actual weight” – up to 400 mg/day
– “is appropriate,” said lead investigator Dr
Laura Durcan, now a rheumatology fellow
at the University of Washington in Seattle.
Rheumatologists generally opt for weight-
based dosing, but ophthalmologists prefer to
use ideal body weight to prevent overdoses
in obese patients at an increased risk for
retinopathy. The Hopkins team seems to
have found a workable middle ground –
weight-based dosing up to a maximum of
400 mg/day, which is considered safe in a
lean person of about 136 pounds.
Three months after being prescribed hy-
droxychloroquine, however, just 56% of the
patients were at a therapeutic level of 500 ng/
mL or more. The rest were either subthera-
peutic at 15–500 ng/mL or had no detectable
hydroxychloroquine in their blood.
The problemwas adherence. “We were hor-
rified” at “how poorly compliant patients were
in a cohort that is very well educated about
the benefits of medication, and surprised by
how few of themwere taking their pills as pre-
scribed,” Dr Durcan said at the annual meet-
ing of theAmericanCollege of Rheumatology.
Even so, it’s well known that drug adher-
ence is a problem with chronic disease, so
“I think our numbers would be similar in
any lupus cohort,” she said.
The researchers fixed the problem by
insisting patients activate their Hopkins
electronic health record portal, so they could
check their blood work. If their numbers were
low, they saw a reminder on their results page
to take their pills every day, and the record
system added a note to their chart to bring up
adherence during the next office visit.
That’s all it took for most patients. By
about their third office visit, 80% of patients
were in the therapeutic range. “If you have a
measurable outcome, you can significantly
impact patient adherence,” Dr Durcan said.
There was a trend towards higher disease
activity with lower drug levels. The 13% of
patients with undetectable levels at their
first hydroxychloroquine checkup had a
mean Systemic Lupus Erythematosus Dis-
ease Activity Index (SLEDAI) score of 2.92,
and the 31% who were subtherapeutic had a
mean SLEDAI of 2.36. The 56% of patients
in the therapeutic range had a mean SLE-
DAI of 2.20 (P = 0.04 for trend).
Those differences probably didn’t mean
much clinically, but “it’s important to note
that the impacts of therapy go beyond the
immediate impact on disease activity,”
Dr Durcan said.
Over 90% of the subjects were women,
and most were over 30 years old. The few
men in the study were a bit more likely to
have therapeutic levels of hydroxychloro-
quine 3 months after it was prescribed.
Hopkins uses in-house mass spectrometry
to measure hydroxychloroquine concentra-
tions in whole blood, believing it is more
accurate and meaningful than the serum
levels used elsewhere.
The investigators have no relevant disclosures.
The work was funded by the US National
Institutes of Health.
The guidelines recommend
hydroxychloroquine as the first step
for inflammatory musculoskeletal
pain, followed, as needed, by
methotrexate, steroids, and other
options. Azathioprine is a good option
for recalcitrant musculoskeletal pain,
as well as organ involvement.
VEBs predict
sudden cardiac
death in systemic
sclerosis
BY M. ALEXANDER OTTO
Frontline Medical News
At the American College of Rheumatology
annual meeting, San Francisco
In systemic sclerosis, more than 1190 ventricular
ectopic beats per 24 hours of Holter monitoring was
100% sensitive and 83% specific for sudden cardiac
death or defibrillator implantation within a year in a
prospective cohort study from the Catholic University
of the Sacred Heart in Rome.
Twenty-four hour Holter monitoring needs to be
“part of the routine evaluation in SSc [systemic scle-
rosis] with suspicious cardiac involvement” so that
patients get implantable cardioverter defibrillators
(ICDs) in time, said investigator Dr Giacomo De
Luca, a rheumatologist at the university.
Arrhythmias secondary to myocardial fibrosis are
killers in SSc and sometimes strike patients with
mild heart symptoms such as dyspnoea that are eas-
ily mistaken for lung involvement, and patients who
fall outside of traditional ICD indications such as
ejection fractions below 35%. Because of that, “bet-
ter risk stratification is desperately needed” to catch
patients early “and prevent sudden cardiac death
[SCD],” Dr De Luca said at the annual meeting of
the American College of Rheumatology.
Holter monitoring isn’t a part of routine SSc workup,
but Dr De Luca and his team think it might solve the
arrhythmia problem. Ventricular ectopic beats (VEBs)
over 1,190 per 24 hours have an “excellent positive
predictive value. [They are a] warning biomarker of
major arrhythmias,” he said.
The conclusions come from 100 SSc patients with
new-onset cardiac symptoms, generally palpitations
and mild dyspnoea, but also some with chest pain or
heart failure signs. The subjects wore Holter monitors
for 24 hours and then were followed for a mean of 2
years.
At baseline, 56 patients had Holter abnormalities.
VEBs were the most common, present in 24 patients at
a “strikingly high” mean of 2046/24 hours. The number
of VEBs correlated with cardiac troponin T (cTnT)
levels and inversely correlated with left ventricular
ejection fractions.
The team also found 19 patients with supraventricu-
lar ectopic beats, 14 with episodes of supraventricular
paroxysmal tachycardia, and 11 with runs of nonsus-
tained ventricular tachycardia, but those problems
didn’t prove to be predictors of SCD.
During follow-up, seven patients met the study’s
combined primary endpoint of SCD or ICD implan-
tation. Five died and two had implants at a mean of
8.5 months. The age range was 32–77 years, and me-
dian baseline ejection fraction was 40%, but ejection
fractions ranged widely and were normal in some,
indicating that they don’t reliably predict SCD in SSc
patients. None of the seven subjects had pulmonary
arterial hypertension; it was ruled out by right heart
catheterisation.
Compared with the overall cohort, the seven pa-
tients who met the primary endpoint had lower ejec-
tion fractions and higher numbers of VEBs – all were
above 1,000/24 hours at baseline – plus higher levels
of cTnT and NT-proBNP [N-terminal prohormone
brain natriuretic peptide].
The 1,190 VEBs/day cutoff emerged on a receiver op-
erating characteristic (ROC) analysis that proved robust
(AUROC = 0.94, P < 0.0001); cTnT above 0.014 ng/
mL and right bundle branch block were independent
predictors of VEBs above the cutoff, but prolonged
baseline QT intervals had no prognostic value.
The investigators had no disclosures.
Rheumatology News • Vol. 4 • No. 1 • 2016 10
LUPUS/CONNECTIVE TISSUE DISEASES