Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis

Abstract

IMPORTANCE Randomized clinical trials (RCTs) and meta-analyses of sublingual immunotherapy (SLIT) for the treatment of seasonal allergic rhinoconjunctivitis (SARC) have shown a modest clinical benefit compared with placebo. Furthermore, indirect comparison by meta-analyses showed that subcutaneous immunotherapy is more effective than SLIT. Despite these data, SLIT has become the most prescribed treatment of SARC in Europe in recent years, and it was approved by the US Food and Drug Administration for the treatment of SARC to grass pollen in the United States on April 1, 2014. OBJECTIVE To assess the efficacy and safety of the grass pollen sublingual tablets licensed as drugs in the treatment of patients with SARC to grass pollen. DATA SOURCES Computerized bibliographic searches of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (from inception to April 30, 2014) were supplemented with a manual search of reference lists. STUDY SELECTION Randomized clinical trials were included if they compared the grass pollen SLIT tablets approved by regulatory authorities in the European Union and the United States for SARC with placebo. DATA EXTRACTION AND SYNTHESIS Data on populations, interventions, and outcomes were extracted from each RCT according to the intent-to-treat method by 2 independent observers and were combined using the method by DerSimonian and Laird. MAIN OUTCOMES AND MEASURES The primary end point was the difference in the symptom score and medication score between SLIT and placebo. We pooled data using random-effects meta-analysis, with standardized mean differences (SMDs) and 95% CIs reported. RESULTS Data were available in 13 RCTs for the symptom score (4659 patients) and in 12 RCTs for the medication score (4558 patients). We found a small treatment benefit in the symptom score (SMD, −0.28; 95% CI, −0.37 to −0.19; P < .001) and in the medication score (SMD, −0.24; 95% CI, −0.31 to −0.17; P < .001). Adverse events were reported in 1384 of 2259 patients (61.3%) receiving SLIT and in 477 of 2279 patients (20.9%) receiving placebo. Seven patients in the SLIT group reported treatment-related adverse events requiring epinephrine. CONCLUSIONS AND RELEVANCE Findings show a small benefit of the grass pollen sublingual tablets in reducing symptoms and in decreasing the use of symptomatic medication (antihistamines and corticosteroids) in patients with SARC. Considering the low magnitude of the benefit, the convenience and easy administration do not seem to be sufficient reasons for the choice of SLIT.

Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review

“…Furthermore, the benefit of AIT was mainly reported in studies with shorter follow-up, while studies with longer follow-up, which is critical for this specific outcome, did not show any difference. No study reported on the possible correlation between the onset of new sensitizations and the primary clinical benefit of AIT (very small for SLIT), (3,50,51) that is, the reduction in symptom or medication scores, rendering any inference impossible as to the primary efficacy and long-term benefit of AIT.…”

“…Allergen immunotherapy (AIT) has been proven effective, with variable clinical benefit, in reducing symptoms and the use of antisymptomatic medications in patients with allergic rhinoconjunctivitis and asthma (1)(2)(3). In contrast to antisymptomatic medications, AIT, administered by the subcutaneous (SCIT) or sublingual (SLIT) route in clinical practice, may have persisting effects after its discontinuation, as it acts through a modification of the immune response.…”

Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an umbrella review

“…Six reviews provided data comparing SLIT with placebo for an outcome of interest, 20,21,24,25,29,33 2 provided data for SCIT versus placebo, 25,29 and 2 provided data comparing SCIT and SLIT. 25,29 Total combined symptom-medication score: Total combined symptom-medication scores were assessed in 3 reviews of SLIT and 1 review of SCIT 20,24,29 ( Figure 2, Table 3).…”

“…Symptom score: Three reviews reported a significant improvement in symptom score among patients taking SLIT compared to placebo (SMD range -0.49 to -0.28; I 2 = 42%-81%), 21,29,33 and 2 reviews reported improvements with SCIT compared to placebo (SMD range -0.65 to -0.30; I 2 = 57%). 25,29 Two reviews compared the efficacy of SCIT versus SLIT via indirect treatment comparisons.…”

“…Medication score: Three reviews reported significant improvement in medication scores among patients taking SLIT compared to placebo (SMD range -0.32 to -0.24), with moderate heterogeneity (I 2 = 22%-50%) 21,29,33 (Table 3). One review reported a significant improvement in medication score associated with SCIT compared to placebo (SMD -0.55, 95% CI -0.75 to -0.34; I 2 = 57%).…”