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because of side effects was significantly more frequent in the
solifenacin group (27.3% vs 7.9%) and discontinuation
because of lack of efficacy was significantly more frequent
in the mirabegron group (36.8% vs 5.6%).
What are the take home messages? Mirabegron, except
in one report, does appear to have a higher persistence rate
at 1 yr than any of the antimuscarinics, although all the
rates are still very suboptimal. Why is there a difference and
why does this become apparent early in treatment (by 90–
100 d), after which the relative rates of discontinuation
remain constant? Aside from the fact that the OAB drugs
treat a symptom-syndrome whose components affect
health-related quality of life as opposed to systemic
diseases, which may be relatively asymptomatic but
associated with shorter longevity, the list rapidly distills
to efficacy, tolerability, or both. Clever trial designs and
statistical manipulations aside, the efficacy of mirabegron
is, in my opinion, similar to the antimuscarinics at best. To
level the playing field, look at data from the Food and Drug
Administration–approved package inserts for solifenacin,
fesoterodine, and mirabegron. The efficacy of mirabegron
compared to placebo in terms of incontinence episodes and
daily micturition frequency (only the 50-mg dose was used
in the trials submitted) is numerically small, and the same
applies to solifenacin and fesoterodine relative to the
individual baselines for those parameters. Converting these
differences to percentages makes the differences look
greater, of course, until one looks at the actual figures from
which these percentages are derived. For volume voided,
the differences relative to placebo are significantly greater
for solifenacin and fesoterodine than for mirabegron.
Whether this difference in volume voided would be
perceptible, considering the lack of significant difference
in incontinence episode reduction and micturition frequen-
cy, is debatable. In sharp contrast, the rates for dry mouth,
constipation, and blurred vision compared with placebo are
much greater for the antimuscarinics than for mirabegron.
Mirabegron is indistinguishable from placebo except for
nasopharyngitis and ‘‘hypertension’’, both of which are
different, but only minimally so, from placebo. Considering
the minimal differences in efficacy parameters except for
volume voided, and the marked difference in adverse
events, it seems tome that the only logical conclusion is that
the initial (at 90–100 d) spread in discontinuation figures
between the antimuscarinics and mirabegron is due to the
greater incidence of adverse events, which appear relatively
quickly with the antimuscarinics, with a stable descent for
all drugs out to 1 yr because of similar factors affecting both
types of drug. I would suggest that irrespective of other
factors, patients did not perceive a difference between the
drugs with respect to efficacy. In a previous article, Chapple
et al suggested that we need better standardization
measures in all outcome evaluations to increase compara-
bility and to standardize the assessment between different
treatments. Such an evaluation should encompass satisfac-
tion, symptoms, health-related quality of life, and adverse
events as a minimum. OAB clinical trials have characteris-
tically reported individual symptoms in isolation and
compared these as primary outcomes, the most frequent
being urgency urinary incontinence episodes and some
aspect of urgency. However, as Chapple et al point out,
this approach may not portray true therapeutic outcomes or
reflect what matters most to patients. Such a system of
evaluation carried out not only at the usual 12-wk limit of
drug trials but also at 6 and 12 mo, and even beyond, would
be most helpful in this regard.
The quality of results for drug therapy ultimately depends
on taking the drug. The reasons for lack of persistence and
adherence to prescribed therapy need to be further explored.
Evidence-based programs to address the underlying causes
of lack of persistence and adherence in OAB and other more
serious medical priority areas must be developed. The
reason why a drug is prescribed (to treat or prevent a
consequence of a medical condition, even if the patient is
relatively asymptomatic, or to treat symptoms, as in the case
of OAB) must be thoroughly explained to the patient, along
with realistic expectations for efficacy and adverse events. In
the case of OAB, I suspect that a relative lack of efficacy for
correcting what the patient feels is important, combined, in
the case of antimuscarinics, with anticholinergic side effects,
which will become apparent relatively early in a susceptible
individual, are the major reasons for discontinuation. The
data cited here tell us, in effect, that our pharmacologic
therapy for OAB is moderate at best.
Conflicts of interest: The author is a consultant for Allergan, Aquinox,
Axonics, Medtronics, Serenity, and Velicept.
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