Guidelines Issued for Sublingual Immunotherapy

From Medscape Medical News
Laurie Barclay, MD

December 21, 2009 — Evidence-based guidelines for use of sublingual Immunotherapy (SLIT) are issued in the World Allergy Organization Position Paper 2009, reported in the November issue of the World Allergy Organization Journal. This article is co-published as a supplement to the December 2009 issue of Allergy.

"...SLIT has gained wide acceptance in many European countries and has raised the level of interest in immunotherapy among practicing allergists and primary care physicians," write World Allergy Organization (WAO) chair G. Walter Canonica, MD, from the University of Genoa in Genoa, Italy, and colleagues.

"Large pivotal double-blind, placebo-controlled, randomized clinical trials have confirmed the efficacy and safety of SLIT, although some negative trials have also been published. In 2008, the...[WAO] Board Of Directors decided that it was important and timely to advise our global constituents on the current State of the Art on SLIT, to offer consensus on its use based on currently available evidence and expert opinion, and to develop practice parameters."

On January 22-23, 2009, WAO convened a global consensus meeting on SLIT in Paris, France. Regional, national, and affiliate WAO member societies were represented, as were nongovernmental organizations working in the field of allergy, as well as Allergic Rhinitis and its Impact on Asthma, the European Federation of Allergy and Airway Diseases Patients Association, the International Primary Care Respiratory Group, the International Association of Asthmology, the Global Allergy and Asthma European Network, and others. The meeting and position statement were totally independent from funding or other influence of the pharmaceutical or the allergen extract/vaccine industries.

Topics in the Position Statement

In addition to offering guidelines for clinical practice using SLIT, the meeting aimed to identify unmet needs by analyzing recent and ongoing SLIT clinical trials and by recommending additional studies needed and appropriate methodology.

Topics included in the SLIT position statement are the following:

• Introduction and historical background regarding SLIT.
• Allergen-specific immunotherapy.
• Mechanisms of SLIT.
• Clinical efficacy of SLIT.
• Safety of SLIT.
• Effect of SLIT on the natural history of respiratory allergy.
• Use of SLIT in children.
• Guidelines and recommendations concerning SLIT.
• Definition of patient selection for SLIT.
• The future of immunotherapy in the community care setting.
• Methodology of clinical trials evaluating SLIT.

In determining their recommendations for SLIT, the WAO noted that there have been several adequately powered, well-designed, randomized clinical trials. Findings from these studies suggest that high-dose, sublingual, specific immunotherapy is effective in carefully selected patients.

Appropriate indications for use of SLIT include rhinitis, conjunctivitis, and/or asthma caused by pollen and/or house dust mite (HDM) allergy. Although the safety of SLIT has been confirmed in randomized clinical trials, many patients report local adverse effects. Systemic reactions have been reported only rarely.

In appropriate patients, SLIT may be considered as initial treatment; failure of pharmacologic treatment is not required before starting therapy. Special SLIT indications exist in patients whose allergies are uncontrolled with optimal pharmacotherapy, patients in whom pharmacotherapy induces undesirable adverse effects, patients refusing injections, and patients who do not want to be receiving constant or long-term pharmacotherapy.

Immunotherapy Recommendations

To reduce risk and improve efficacy of SLIT, the WAO recommends the following considerations for starting immunotherapy:

• There should be the presence of a demonstrated immunoglobulin E (IgE)–mediated disease, with positive skin test results and serum-specific IgE to an allergen concordant with clinical symptoms.
• There should be documentation that the symptoms can be explained by specific sensitivity, based on appearance of symptoms related to exposure to the allergen(s) identified by allergy testing. Optional confirmation may include allergen challenge with the relevant allergen(s).
• Severity and duration of symptoms should warrant use of SLIT, with confirmation from objective parameters such as missing time from work or school. For rhinoconjunctivitis, patients should have subjective symptoms of sufficient severity and duration. For asthma, the control questionnaire should not show uncontrolled asthma, and pulmonary function testing is required to exclude patients with severe asthma. Pulmonary function should be monitored during therapy.
• SLIT therapy should only be started in settings where standardized or high-quality vaccines are available. Only specialists should prescribe specific immunotherapy. Subcutaneous immunotherapy should be administered only by physicians trained to manage systemic reactions if anaphylaxis occurs.
• Although SLIT is administered at home, patients should be educated regarding possible risks and how to control adverse effects that may develop.
• Patients with a single allergen sensitivity are more likely to benefit from specific immunotherapy vs patients sensitive to multiple allergens, but more data are needed in this area.
• Specific immunotherapy will not benefit patients with nonallergic triggers.
• For safety reasons, asthmatic patients must be asymptomatic when receiving SLIT injections. Asthmatic patients with severe airways obstruction are more likely to have lethal adverse reactions.
• To maximize the efficacy and safety of SLIT in asthmatic patients, forced expiratory volume in 1 second with pharmacologic treatment should reach at least 70% of predicted values.

World Allergy Organization J. 2009;2:233-281.
Allergy. December 2009, supplement.

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