Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis

Abstract

IMPORTANCE Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. OBJECTIVE To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. DESIGN, SETTING, AND PARTICIPANTSA randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.INTERVENTIONS Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 μg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 μg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). MAIN OUTCOMES AND MEASURESTotal nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. RESULTS Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [P = .75]).CONCLUSIONS AND RELEVANCE Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.

Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

“…Around 30 patients per treatment arm finished the study, and while SCIT‐treated patients had significantly reduced nasal symptoms scores in year 1 and year 2 of treatment, SLIT treatment only achieved this in year 2 of treatment. After treatment discontinuation, SLIT was not effective in reducing nasal symptoms scores, underscoring the need for prolonged treatment periods or optimized allergen vaccines for SLIT application . Interestingly, spIgG4 responses were stronger and showed faster kinetics in SCIT treatment compared to SLIT, while SLIT but not SCIT induced an increased spIgE titres, indicating that the ratio of spIgG over IgE was much higher in SCIT compared to SLIT, which was also reflected in the early allergic skin response upon allergen challenge.…”

Der p 1‐specific regulatory T‐cell response during house dust mite allergen immunotherapy

“…Allergen‐specific CD45RB low CD27 − CRTH2 + CD161 + CD49d + T cells (Th2A) are more frequent in allergic patients compared to nonallergic individuals and suggesting a role for the control of clinical allergic reactions by these cells that are induced by immunotherapy . Also in long‐term grass‐specific immunotherapy, a clinical improvement during 2 years of treatment has been associated with the decrease in numbers of the allergen‐specific CRTH2 + CCR4 + CD27 − CD4 + Th2 cells . Indeed, there are now many studies confirming the role of decreased Th2 responses in the control of allergic disease and Treg cells play an essential role in the suppression of Th2 cells.…”

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis

“…83 In a recent study, either SCIT or SLIT tablets were effective compared to placebo over 2 years, but 2 years were insufficient for long-term efficacy as measured 1 year off treatment. 65 In another adult study, participants randomized to 3 years of ragweed continued to benefit after 2 years post-SCIT. 178 Similarly, children randomized to 3 or 5 years HDM SCIT had similar outcomes at 5 years.…”