Sublingual Immunotherapy May Be Safe, Effective for Allergic Rhinitis

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Sublingual

Immunotherapy May Be Safe, Effective for Allergic

Rhinitis CME/CE

News

Author: Laurie Barclay, MD

CME Author: Penny Murata, MD

Authors and Disclosures

CME/CE Released: 12/13/2010; Valid for

credit through 12/13/2011

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Target Audience

This article is intended

for primary care clinicians, allergists,

immunologists, and other specialists who

provide care to adults and children with

allergic rhinitis.

Goal

The goal of this activity

is to provide medical news to primary care

clinicians and other healthcare professionals

in order to enhance patient care.

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Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed

no relevant financial relationships.

Brande

CME Clinical Editor, Medscape, LLC

Disclosure: Brande has disclosed

no relevant financial relationships.

Penny Murata, MD

Clinical Professor, Pediatrics, University of

California, Irvine, California

Pediatric Clerkship Director, University of

California, Irvine, California

Disclosure: Penny Murata, MD, has disclosed no

relevant financial relationships.

Fleischman

CME Program Manager, Medscape, LLC

Disclosure: Fleischman has disclosed no

relevant financial relationships.

Laurie E. Scudder, DNP, NP

Nurse Planner, Continuing Professional

Education Department, Medscape, LLC; Clinical

Assistant Professor, School of Nursing and

Allied Health, Washington University,

Washington, DC

Disclosure: Laurie E. Scudder, DNP, NP, has

disclosed no relevant financial relationships.

Learning Objectives

Upon completion of this

activity, participants will be able to:

Describe the efficacy of sublingual

immunotherapy for allergic rhinitis in

adults and children.

Describe the safety of sublingual

immunotherapy for allergic rhinitis in

adults and children.

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December 13, 2010 — Sublingual

immunotherapy may be safe and effective for

allergic rhinitis, according to an updated review

reported online December 8 in the Cochrane

Database of Systematic Reviews. The previous

systematic review on this topic was first

published in The

Cochrane Database System Reviews.

"Allergic rhinitis is a common

condition which can significantly impair quality

of life," write Suzana Radulovic, from the LEAP

Study Team, Paediatric Allergy Research Department

in London, United Kingdom, and colleagues.

"Immunotherapy by injection can significantly

reduce symptoms and medication use but its use is

limited by the possibility of severe systemic

adverse reactions. Immunotherapy by the sublingual

route is therefore of considerable interest."

The goal of this systematic

review was to assess the effectiveness and safety

of sublingual immunotherapy for allergic rhinitis.

Through August 14, 2009, the reviewers searched

the Cochrane ENT Group Trials Register; CENTRAL

(2010, Issue 3); PubMed; EMBASE; CINAHL; Web of

Science; BIOSIS Previews; Cambridge Scientific

Abstracts; mRCT; and other sources for published

and unpublished randomized, double-blind,

placebo-controlled trials of sublingual

immunotherapy in adults and children. Other

criteria for studies to be included in the review

were use of symptom and medication scores in

adults or children, and reporting of adverse event

data.

Studies were selected by 2

independent authors, who also examined the risk

for bias. Data were extracted by 1 reviewer,

rechecked by 2 other reviewers, and combined with

use of a random-effects model to determine the

standardized mean difference (SMD).

Of 60 randomized controlled

trials identified and included in the review, 49

were of sufficient methodologic quality to pool

the data in meta-analyses and enrolled a total of

2333 participants given sublingual immunotherapy

and 2256 given placebo. A total of 11 studies used

sublingual tablets, 35 used sublingual drops, and

3 used both and were excluded from analysis.

Compared with participants

receiving placebo, those receiving sublingual

immunotherapy had significantly fewer symptoms

(SMD, −0.49; 95% confidence interval [CI], −0.64

to −0.34; P <

..00001) and lower medication requirements (SMD,

−0.32; 95% CI, −0.43 to −0.21; P <

..00001).

Within the subgroup of 15

trials looking exclusively at children, the

treatment effect appeared to be similar to that

seen in adults, especially when symptom scores

were considered.

Severe systemic reactions or

anaphylaxis were not reported in any of the 49

included trials. Although some systemic reactions

were reported, adrenaline was not needed for

treatment in any of these cases.

"This updated review

reinforces the conclusion of the original 2003

Cochrane Review that sublingual immunotherapy is

effective for allergic rhinitis and has been

proven to be a safe route of administration," the

review authors write.

Limitations of this study

include significant heterogeneity among the

included studies and inability to differentiate

the effects of various dosages.

"The optimum dose and duration

of therapy remains an unanswered question and it

is unlikely that meta-analysis will provide the

answers," the review authors conclude. "The

mechanism of action of both injection and

sublingual immunotherapy remain under

investigation, and injection immunotherapy has

been proven to lead to long-term changes in the

immunological response to allergen that may

persist for years following discontinuation."

One of the study authors

has disclosed a financial relationship with the

Immune Tolerance Network. The Department of

Upper Respiratory Medicine, National Heart &

Lung Institute, London, United Kingdom, headed

by Professor Durham, has received financial

support from ALK Abello, Horsholm, Denmark

(makers of allergen extracts).

Cochrane Database Syst Rev.

Published online December 8, 2010.

Additional Resources

The Cochrane Library provides 7 reviews in the

area of Allergic Rhinitis on their

website.

Clinical Context

Allergic rhinitis has been

reported in up to 40% of people worldwide.

According to the 2008 guidelines on Allergic

Rhinitis and its Impact on Asthma (ARIA),

published in the April 2008 supplemental issue

of Allergy,

specific immunotherapy is recommended for

patients with severe allergic rhinitis who do

not respond to allergen avoidance and

pharmacotherapy.

The 2003 Cochrane Review of

sublingual immunotherapy for allergic rhinitis

by and colleagues, published in the 2003

issue of the Cochrane

Database of Systematic Reviews, included

22 randomized, placebo-controlled trials.

Sublingual immunotherapy was noted to be

effective and was not associated with systemic

reactions.

This update of the 2003

Cochrane Review evaluates the efficacy and

safety of sublingual immunotherapy for allergic

rhinitis in adults and children.

Study Highlights

A search of the literature included the

Cochrane ENT Disorders Group Trials Register,

the Cochrane Central Register of Controlled

Trials, PubMed, EMBASE, CINAHL, LILACS,

KoreaMed, IndMed, PakMediNet, CAB Abstracts, Web

of Science, BIOSIS Previews, China National

Knowledge Infrastructure, Current Controlled

Trials, International Clinical Trials Registry

Platform, Google, reference lists, and other

sources for published and unpublished data

through August 14, 2009.

Inclusion criteria were randomized,

double-blind, placebo-controlled clinical trials

that assessed the efficacy and safety of

sublingual immunotherapy in adults and children

with allergic rhinitis and a Jadad score greater

than 3 of 5.

60 studies were identified.

49 studies were included in the efficacy

meta-analysis.

11 studies lacked efficacy data but had

adverse event data.

Subjects had allergic rhinitis with or without

allergic conjunctivitis or allergic asthma.

Allergens were identified by skin prick tests

or high specific immunoglobulin E results.

34 studies had adult participants, and 15

studies had children as participants.

The primary outcome measures were symptom

scores and medication scores.

Symptom scores were assessed by diaries,

visual analog scales, number of well days, or

overall assessment.

Medication scores assessed the use of

antihistamine tablets, nasal sprays, and eye

drops.

Secondary outcome measures were serum

immunoglobulin E and immunoglobulin G levels;

allergen sensitivity of the eye, nose, or skin;

and reports of adverse events.

Subgroup analysis was conducted for seasonal

vs perennial allergens, children vs adults,

major allergen dose (< 5 μg vs 5 to 20 μg vs

> 20 μg), duration of immunotherapy (< 6

months vs 6 - 12 months vs 12 months),

individual allergens (house dust mite, grass

pollen, Parietaria,

ragweed, tree), sublingual spit vs swallow, and

sublingual drops vs tablets.

Symptom scores improved more in 2333 patients

receiving sublingual immunotherapy vs 2256

patients receiving placebo. The SMD was −0.49 (P <

..00001), based on 49 studies.

Medication scores improved more in 1737

patients receiving sublingual immunotherapy vs

1642 patients receiving placebo (SMD, −0.32; P <

..00001), based on 38 studies.

Serum-specific immunoglobulin E levels

increased in 675 patients receiving sublingual

immunotherapy vs 659 patients receiving placebo

(SMD, 0.27; P =

..05), based on 14 studies.

Total serum-specific immunoglobulin G levels

increased in 286 patients receiving sublingual

immunotherapy vs 304 patients receiving placebo

(SMD, 0.95; P <

..00001), based on 3 studies.

Serum-specific immunoglobulin G4 levels

increased in 588 patients receiving sublingual

immunotherapy vs 599 patients receiving placebo

(SMD, 0.46; P <

..00001).

Allergen sensitivity, measured by skin prick

test results and nasal reactivity, did not

significantly differ between the sublingual

immunotherapy group and the placebo group.

25 studies could not be included in adverse

event analysis.

Local adverse events, including labial edema,

buccal pruritus, buccal or lingual edema, and

throat irritation, were more common in the

sublingual immunotherapy group vs the placebo

group.

Adverse events leading to treatment

discontinuation occurred in 41 of 824 patients

in the sublingual immunotherapy group and 12 of

861 patients in the placebo group, with local

reactions occurring more than systemic

reactions.

No adverse events required adrenaline use.

No fatalities occurred.

Systemic adverse events were mild or moderate.

No severe systemic adverse events or

anaphylaxis events occurred.

Subgroup analysis of symptom scores showed

more improvement in the sublingual immunotherapy

group vs the placebo group for all subgroups

except for a major allergen content of less than

5 μg.

Subgroup analysis of medication scores showed

more improvement in the sublingual immunotherapy

group vs the placebo group for all subgroups

except for perennial allergens, children, house

dust mite allergen, and sublingual drops.

Clinical Implications

In adults and children with allergic rhinitis,

sublingual immunotherapy is effective in

reducing symptoms and the need for medication.

In adults and children who receive sublingual

immunotherapy for allergic rhinitis, reported

adverse events include local and systemic mild

and moderate events, but no severe systemic

reactions, anaphylaxis, or the need for

adrenaline.

CME Test

According

to this review of patients with allergic

rhinitis, sublingual immunotherapy was

associated with which of the following

outcomes?

Reduction

in symptoms, but not the need for medication

Reduction

in the need for medication, but not symptoms

No

reduction in symptoms or the need for

medication

Reduction

in both symptoms and the need for medication

A

30-year-old patient with allergic rhinitis

unresponsive to medications will begin

sublingual immunotherapy. Compared with

placebo use, sublingual immunotherapy is most likely

to be linked with which of the following

adverse events?

Buccal

pruritus

Need for

adrenaline

Anaphylaxis

Severe

systemic reaction

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