Journal reading: Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma

Journal of the American Academy of Dermatology
Volume 78, Issue 2, Pages 363-369 (February 2018)
Presenter: Chu-Feng WU
2018/1/26 Derm, VGHKS

Copyright © 2017 American Academy of Dermatology, Inc. Terms and Conditions
Journal of the American Academy of Dermatology 2018 78, 363-369DOI: (10.1016/j.jaad.2017.09.053) presented by Chu-Feng WU
Preface
•
Common
but
difficult
to
treat
•
Exacerbating
factors
Exposure
to
sunlight,
oral
contraceptives,
and
pregnancy,

affecting
more
in
Latino
females
•
Few
controlled
studies
exist
•
In
Asian,
tranexamic
acid
has
been
reported
effective
•
Psychologically
debilitating
in
QoL

•
An
antifibrinolytic
agent
•
Originally
for
menorrhagia
and
bleeding
diathesis
Tranexamic acid (TA)

Objective
• Primary objective
to evaluate whether TA plus sunscreen improved
melasma in comparison with placebo group on the
basis of the mMASI score.
• Secondary end points
1. Improvement in melanin index and QoL
2. Adverse effects were also documented.
Expectation: 3 or more points lower than that in the placebo group at
12 weeks and 2 or more points lower than that in the placebo group at
24 weeks. PASS 12 software was used to perform the sample size
estimates.

Methods
Inclusion creteria:
• Female
• Age 18 or older
• Moderate or severe melasma
Moderate melasma:
mMASI score of 5.8 to 7.9
Severe melasma:
mMASI score of 8 or higher

From: Interpretability of the Modified Melasma Area and Severity Index (mMASI)
JAMA Dermatol. 2016;152(9):1051-1052. doi:10.1001/jamadermatol.2016.1006
Determination of the Modified MASI (mMASI) Score

Listed by the
US Food and
Drug
Administration
as
contraindication

• Filled out a quality of life (QoL) survey in English or Spanish.
• Photographed, screened for side effects, a pill count and mMASI score
• Follow up at 1st, 2nd, 3rd, 6th months

Journal of the American Academy of Dermatology 2018 78, 363-369DOI: (10.1016/j.jaad.2017.09.053) presented by Chu-Feng WUJournal of the American Academy of Dermatology 2018 78, 363-369DOI: (10.1016/j.jaad.2017.09.053)
At
first
3
months,

250
mg
of
TA
or

placebo
were
given

BID,
based
on
a

review
of
published

studies
Fig
1.
Consolidated
Standards
of
Reporting

Trials
(CONSORT)
flow
diagram.

For
the
second
3

months,
sunscreen

alone.
44

Results
Fig
2.
Improvement
in
modified
melasma
area
and

severity
index
(mMASI)
scores
in
patients
with
moderate
and
severe

melasma
treated
with
tranexamic
acid
(TA)
versus
placebo.

TA
group Placebo
3
months 49%(4.2) 18%(1.4)
6
months 26%(2.2) 19%(1.6)
TA
group Placebo
Moderate 45%(2.9) 16%(1.0)
Severe 51%(5.9) 19%(1.9)
The
interactions
of
time
by
treatment
(TA
vs
placebo
[P
=
.0003])

Time
by
melasma
(moderate
vs
severe
[P
=
.0312])

Fig
3.Baseline
of
moderate group

Journal of the American Academy of Dermatology 2018 78, 363-369DOI: (10.1016/j.jaad.2017.09.053)
Fig
4.after
3
months
of
tranexamic
acid

Fig
5.Baseline
of
severe group

Journal of the American Academy of Dermatology 2018 78, 363-369DOI: (10.1016/j.jaad.2017.09.053)
Fig
6.after
3
months
of
tranexamic
acid

Discussions
•
No
evidence
to
support
an
increased
risk
for

thromboembolic
events
at
these
doses.
headaches
nausea
back
pain
•
Even
women
taking
high
doses
of
TA
for
menorrhagia,

usually
3.9
to
4
g/d
for
5
days
per
month,
have
few

adverse
effects.
Common
side
effects
menstrual
irregularity

2.Hx
of
spontaneous
miscarriage
561
patients

40
pts

(7.1%)

1
case
of

DVT
1.Familial
protein
S
deficiency
3.Family
hx
of
thromboembolic

phenomenon
in
2
siblings.

HQ
4%
cream
only
250
mg
of
oral
TA,
TID

+

hydroquinone
(HQ)
4%
cream
nightly

• No
significantly
different
in
relapse
rate
(30%
vs
26%)
and
side
effects
• Treatment
satisfaction
was
higher
in
the
intervention
group
.

51%
reduction

33%
reduction

mMASI
score

the intervention group 3
months
later

• Features
of
our
enrolled
patients:

• Satisfied
results
at
first
3
months
in
patients

taking
TA
Capsules：
-‐ Often
seek
helps
for
recalcitrant
disease
-‐ Concomitant
reduction
in
melanin
index
as
well.
-‐ Overall
decrease
with
moderate
and
severe
melasma

-‐ Moderate-‐to-‐severe
melasma
• Interpreting
at
3
months
after
no
TA
therapy:
-‐ Benefits
of
this
medication
were
sustained
in
moderate
group
-‐ Improvement
in
severe
groups
was
lost
with
sunscreen
alone.

-‐ No
significant
difference
in
QoL
between
two
groups.
-‐ Addition
of
HQ
or
triple-‐combination
cream
could

improve
results.
-‐
A
longer
course
of
therapy
may
be
needed
in

patients
with
severe
melasma.
• Further
investigations:

Limitations
•
Lack
of
male
subjects
•
Predominantly
Hispanic
patients
• The
follow-‐up
period
after
treatment

was
only
3
months.

Conclusions
• Oral
TA
250
mg
BID
for
3
months
significantly

improved
moderate-‐to
severe
melasma.
• Severe
melasma
responded
better
than
moderate
ones
• Those
with
severe
melasma
did
not
sustain
their

improvement
after
TA
was
discontinued.
• Sunscreen
alone
improved
melasma
with
modest
effects.
• Longer
treatment
durations
and
follow-‐up
periods

and
combination
of
TA
with
depigmenting
creams

should
be
performed.
• Side
effects
were
mild;
screening
patients
for
risk
of

thromboembolism
before
treatment
is
marked.

Take Home Messeges
•
Tranexamic
acid
should
be
considered

when
patients
with
moderate
to
severe

melasma
who
do
not
respond
to
standard

therapy.
•
Melasma
is
often
recalcitrant
to
therapy.
•
Watch
out
for
contraindications
to
TA.

References
Sheth VM, Pandya AG. Melasma: a comprehensive update:
part I. J Am Acad Dermatol. 2011;65(4):689-697.
Werlinger KD, Guevara IL, Gonzalez CM, et al. Prevalence of
self-diagnosed melasma among premenopausal Latino women
in Dallas and Fort Worth, Tex. Arch Dermatol. 2007;143(3):423-431.
Kim EH, Kim YC, Lee ES, et al. The vascular characteristics of
melasma. J Dermatol Sci. 2007;46(2):111-116.
Resnik S. Melasma induced by oral contraceptive drugs. JAMA.
1967;199(9):601-605.
Pathak MA, Riley FC, Fitzpatrick TB. Melanogenesis in human
skin following exposure to long-wave ultraviolet and visible
light. J Invest Dermatol. 1962;39(5):435-443.
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Journal reading: Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma

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Journal reading: Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma