may edition file

years. The CTS also recommends anti-IL5 therapies in adults
with severe eosinophilic corticosteroid-dependent asthma
in an attempt to decrease or withdraw oral corticosteroids
(OCS).
Benefits ‘at best Incremental’
Omalizumab, mepolizumab, reslizumab, benralizumab,
and dupilumab are currently the five US FDA-approved
monoclonal antibodies that affect the pathways involved
in either allergic or type 2 inflammatory phenotypes of
asthma. Presently, there are no head to head randomized
or observational trials to study the comparative clinical
effectiveness of these mAbs. Estimates from Cochrane
meta-analyses showed that all five drugs reduced the
annual exacerbation rate by about 50% with overlapping
confidence intervals. The average improvement for four of
the drugs, compared with a placebo, is modest and none
of them reach the minimally important difference, although
all were statistically significant. Dupilumab had the largest
reduction in exacerbations and benralizumab the smallest,
according to a meta-analysis by the Institute for Clinical
and Economic Review (ICER), an independent nonprofit
research organisation. The risk for serious
adverse events was low for all five drugs. The only
consistent and common adverse event was
injection-site reactions. The dosing schedule
varies between the drugs. Dupilumab is
given every two weeks, omalizumab is given
every two to four weeks, mepolizumab and
reslizumab are given every four weeks, and after the first
three doses, benralizumab is given every eight weeks.
Notably, none of the drugs prevented most
exacerbations requiring systemic corticosteroids or improved
average daily quality of life to a degree considered clinically
significant. Thus, the overall health benefit for all five drugs
is at best incremental, notes ICER report.
“Unfortunately, the currently available biologics have
not been shown to have disease-modifying properties for
asthma,” comments Dr Nish, who is also the President of
Northeast Georgia Physicians Group (NGPG) — Allergy and
Asthma, GA. Studies have shown that asthma returns to
its previous state of inflammation and pathology over time
once the biologics are stopped, he adds.
The long-term safety and effectiveness of these
drugs, however, is yet to be established particularly in
older patients. For omalizumab and mepolizumab, longterm
extension trials and real-world experience provide
supportive but uncontrolled evidence. Response to therapy
is yet to be well-defined to help guide patients and
clinicians in deciding when to stop one therapy and consider
switching to another.
At what cost?
Biologics comes with high treatment costs. Analysis indicate
that biologic agents provide gains in quality-adjusted
survival over the standard of care alone. Exacerbation
reductions and chronic oral steroid reductions are
potentially the most influential benefit associated with
biologic therapy.
A survey by the Asthma and Allergy Foundation of
America involving 805 Americans living with asthma,
including 185 with severe, uncontrolled asthma, found that
an average of 82% chose effectiveness as a key criterion
while an average of 52% cited cost as a key criterion for
selecting a therapy.
Patients report that their asthma prevents them from
living the life that they want to live, besides impacting their
loved ones. They also fear the side effects of corticosteroids
and want to minimize the use of both systemic and inhaled
corticosteroids as much as possible.
26 / FUTURE MEDICINE / May 2019