PURPOSE OF THE STUDY.
This was a systematic review of the clinical efficacy and safety of sublingual immunotherapy (SLIT) delivered via an aqueous solution. This publication was derived from a Comparative Effectiveness Review by the same authors, commissioned by the U.S. Agency for Healthcare Research and Quality.
Sixty-three randomized controlled trials (RCTs) involving 5131 participants met the inclusion criteria and were included in this systematic review. Ages ranged from 4 to 74 years. Most of the studies were trials of grass and dust mite SLIT. Also included were trials of tree, ragweed, cat, and Alternaria SLIT. All but one of the trials in this report used a single allergen extract for treatment. All of the included studies were required to enroll patients with confirmed allergic rhinoconjunctivitis or allergic asthma with skin or specific immunoglobulin E blood testing. Diagnosis of asthma was required to be by objective criteria (pulmonary function testing) or according to established guidelines.
Multiple databases were searched for the period 1950 to December 22, 2012, for English-language RCTs on the effects of SLIT for allergic rhinoconjunctivitis or allergic asthma. Only studies using allergen formulations available in the United States were included. No trials of sublingual tablets were included. The extreme variability of the published RCTs in dosing and treatment schedules confounded the ability to perform a meta-analysis. There was also great variability in the reporting of the maintenance or cumulative doses delivered and a variety of units were used to report dosing. The studies’ comparator groups were placebo (73% of the studies), another sublingual intervention without a placebo group (14%), or pharmacotherapy without placebo (13%). Primary outcomes of the studies included symptom scores, medication scores, quality of life, and safety. There was no uniform or consistent reporting of safety. Using the Grading of Recommendations Assessment, Development, and Evaluation Working Group guidelines, the evidence for each primary outcome was graded as high, moderate, low, or insufficient. The risk of bias was assessed as per the Cochrane Guidelines. Forty-six studies (73%) received industry support and were considered to have moderate or high bias.
Overall, the authors found moderate evidence across outcomes to support the use of SLIT for allergic rhinoconjunctivitis or asthma. For asthma, the strength of evidence in support of SLIT improving symptoms was graded as high. For allergic rhinoconjunctivitis, the evidence was graded as moderate strength. Evidence was similar in strength to support the use of SLIT in children (<18 years of age). Forty-seven (75%) of the trials mentioned safety. Because of the lack of a standard grading system, the authors concluded the evidence was insufficient to grade safety. Local reactions were more frequent in patients receiving SLIT (range, 0.2%–97.0%) than in the comparator groups (range, 3.0%–38.5%). Systemic reactions were rarely reported, but were more common in the groups receiving SLIT than in comparator groups. There were no reported episodes of anaphylaxis, life-threatening reactions, or death in any treated subjects.
According to published trials, there is moderate strength of evidence supporting the effectiveness of SLIT for allergic rhinoconjunctivitis and asthma. There were significant limitations in the reporting of safety data, but no life-threatening adverse events were noted in the published trials.
As per the accompanying editorial, several unanswered issues remain regarding the use of SLIT. Insufficient data were available to identify optimal dosing strategies. The optimal duration of therapy remains unclear, and the relative benefits of single versus multiple allergen therapy are unclear. These issues must be answered before the Food and Drug Administration is likely to approve SLIT in the United States.
- Copyright © 2013 by the American Academy of Pediatrics