title: Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review.
abstract: OBJECTIVE
  Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization.
  
  
  OBJECTIVE
  To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma.
  
  
  METHODS
  The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence.
  
  
  RESULTS
  Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported.
  
  
  CONCLUSIONS
  The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. slin30@jhmi.edu
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Lin
authors.forename: Nkiruka
authors.initials: N
authors.lastname: Erekosima
authors.forename: Julia M
authors.initials: JM
authors.lastname: Kim
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Catalina
authors.initials: C
authors.lastname: Suarez-Cuervo
authors.forename: Yohalakshmi
authors.initials: Y
authors.lastname: Chelladurai
authors.forename: Darcy
authors.initials: D
authors.lastname: Ward
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Segal
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D006801:Humans; D056687:Off-Label Use; D016032:Randomized Controlled Trials as Topic; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000485:Allergens