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IS SLIT MORE EFFECTIVE THAN ALLERGY
MEDICATIONS?
No direct head-to-head studies comparing the efficacy of SLIT
with medications in the treatment of seasonal or perennial allergic
rhinitis have been published because all SLIT trials have allowed
for rescue medication use. Therefore only indirect comparisons
are possible. An indirect comparison was conducted through a
meta-analysis of large (>100 patients), double-blind, placebo-
controlled trials evaluating the efficacy of SLIT 5-grass pollen/
timothy grass tablet or allergy medications for seasonal allergic
rhinitis.
27
Twenty-eight publications on symptomatic medication
trials and 10 publications on SLIT trials met the inclusion criteria
and were evaluated (total n
5
21,223). The authors stated the
following: ‘‘The SLIT tablets had a greater mean relative clinical
impact than second-generation antihistamine and montelukast
and much the same mean relative clinical impact as nasal
corticosteroids.’’
27
This indirect comparison suggests that SLIT
can be as good or better than as-needed medications.
In addition to providing a similar magnitude of improvement,
SLIT can provide sustained benefits for 2 years after discontin-
uation after 3 years of continuous treatment.
28
Whereas the
medications for allergic rhinitis only alleviate symptoms and do
not provide sustained benefits after discontinuation,
29
SLIT is a
disease-modifying approach that has the potential to affect the
course of the condition over time.
WHAT ARE EFFECTIVE DOSE REGIMENS FOR SLIT?
WHAT HAPPENS IF A DOSE IS MISSED?
The 3 US-licensed products showed comparable efficacy
within the investigated dose ranges. Therefore we recommend
following the instructions in the product PIs, keeping the
following points in mind:
d
Doses are expressed in allergy units that are different for
each product and not comparable. See
Table IV
30-36
for
various optimal maintenance doses in micrograms based
on dose-ranging studies.
d
The 5-grass product is available in 2 strengths (100 and 300
IR). For children and adolescents aged 10 to 17 years, the
dose is increased over the first 3 days (‘‘updosing’’): on day
1, a 100-IR tablet is given; on day 2, two 100-IR tablets are
given; and on day 3 and after, the 300-IR tablet (same as for
adults) is given. For the ragweed and timothy grass
products, children and adults take the same dose (ie, a
single tablet daily over the prescribed time period) with
no updosing.
d
Treatment with the ragweed and timothy products is initi-
ated at least 12 weeks before the expected onset of the sea-
son and continued throughout the season, and treatment
with the 5-grass product is initiated at 16 weeks before
the expected onset of the season and continued throughout
the season (ie, the ‘‘precoseasonal’’ regimen). Some studies
suggest that benefits might be seen if treatment is started at
8 weeks before or at onset of season.
37-39
The timothy
product has an option of continuous year-round treatment.
According to the PI, ‘‘for sustained effectiveness for one
grass pollen season after cessation of treatment, [the
product] may be taken daily for three consecutive years.’’
Regarding missed doses, the PIs for the short ragweed and
timothy grass products state that ‘‘data regarding the safety of
restarting treatment after missing a dose of [the product] are
limited. In the clinical trials, treatment interruptions for up to
seven days were allowed.’’ No data on missed doses are available
for the 5-grass product. The medication guide for patients for all 3
products states the following: ‘‘If you forget to take [the product],
do not take a double dose. Take the next dose at your normal
TABLE II.
Systematic reviews comparing sublingual and subcutaneous immunotherapy
Key findings
Indirect
Head to head
Di Bona et al, 2012
7
Dretzke et al, 2013
8
Chelladurai et al, 2013
9
Kim et al, 2013
10
No. of RCTs
17 SCIT vs placebo
22 SLIT vs placebo
17 SCIT vs placebo
11 SLIT vs placebo
8 SCIT vs SLIT
3 SCIT vs SLIT,
pediatric only
Symptom score
SMD
5
SCIT vs placebo,
2
0.92 (95% CI,
2
1.26 to
2
0.58)
SMD
5
SLIT-D vs placebo,
2
0.25 (95% CI,
2
0.45 to
2
0.05)
SMD
5
SLIT-T vs placebo,
2
0.40 (95% CI,
2
0.54 to
2
0.27)
SSD
5
SCIT vs SLIT,
0.35 (95% Crl, 0.13 to 0.59)
Favoring SCIT
Moderate-grade evidence
Favoring SCIT
Low-grade evidence
Favoring SCIT
Medication score SMD
5
SCIT vs placebo,
2
0.58 (95% CI,
2
0.86 to
2
0.30)
SMD
5
SLIT-D vs placebo,
2
0.37 (95% CI,
2
0.7 to 0.0)
SMD
5
SLIT-T vs placebo,
2
0.30 (95% CI,
2
0.44 to
2
0.16)
SSD
5
SCIT vs SLIT,
0.27 (95% Crl, 0.03 to 0.5)
Favoring SCIT
Low-grade evidence,
no difference in
treatment effectiveness
between SCIT and SLIT
Low-grade evidence
Favoring SCIT
Safety
SCIT: 0.86 AEs/patient
SLIT: 2.13 AEs/patients
Anaphylactic episodes
SCIT/SLIT: 12/1
NR
Local reactions (frequency)
SCIT: 20%
SLIT: 7% to 56%
Anaphylactic episodes
SCIT: 1 SLIT: 0
Local reactions (patients)
SCIT: 3 SLIT: 3
Systemic reactions (patients)
SCIT: 4 SLIT: 0
Anaphylactic episodes
SCIT: 1 SLIT: 0
Adapted from Chelladurai and Lin.
11
AE
, Adverse event;
Crl
, credible interval;
NR
, not reported;
RCTs
, randomized controlled trials;
SLIT-D
, sublingual immunotherapy drops;
SLIT-T
, sublingual immunotherapy
tablets;
SMD
, standardized mean difference;
SSD
, standardized score difference.
J ALLERGY CLIN IMMUNOL
VOLUME
nnn
, NUMBER
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LI ET AL
196