A 2-year course of sublingual immunotherapy (SLIT) for grass pollen allergy failed to beat placebo at improving nasal symptoms at 3-year follow-up, according to results from the GRASS Randomized Clinical Trial. Results were published in JAMA.1 Prior studies showed that a 3-year course of sublingual immunotherapy or subcutaneous immunotherapy decreases the seasonal symptoms of allergic rhinitis and leads to reduced use of allergy medicines for 2 years or more after treatment cessation.
Led by Guy Scadding, PhD, from Imperial College London, the GRASS investigators randomly assigned 106 adults with moderate to-severe seasonal allergic rhinitis to receive sublingual immunotherapy (SLIT), consisting of daily tablets containing 15 μg major allergen Phleum p 5 and monthly placebo injections (36 patients); subcutaneous immunotherapy (SCIT), consisting of monthly injections containing 20 μg Phleum p 5 and daily placebo tablets (36 patients); or matched placebo (34 patients). Nasal response to allergen challenge with timothy grass extract, selected as a surrogate for seasonal outcomes, was assessed using the Total Nasal Symptom Score (TNSS) at baseline and at 1-, 2-, and 3-year follow-up (1 year after withdrawal of treatment). TNSS is a 12-point scale that ranges from 0 (best) to 12 (worst).
Results showed that the SLIT group had a mean TNSS score of 6.36 (95% CI, 5.76-6.96) at baseline and improved to 4.73 (95% CI, 3.97-5.48) at 3 years, whereas the placebo group had a mean TNSS score of 6.06 (95% CI, 5.23-6.88) at baseline and improved to 4.81 (95% CI, 3.97-5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; P =.75) The SCIT group, which served as a positive control, had a mean TNSS score of 6.10 (95% CI, 5.32-6.89) at baseline and improved to 3.96 (95% CI, 3.21-4.71) at 3 years, a difference from placebo of −0.90 (95% CI, −1.96 to 0.16). These results indicated a similar lack of efficacy for 2 years of SCIT at 1 year posttreatment.2 The study was not powered to measure differences between SCIT and SLIT.
“If a 2-year regimen had demonstrated long-term benefits in addition to efficacy, this could have represented cost savings in terms of clinical resources and improved convenience for the patient. Because this was not observed, clinicians should be advised to follow established guidelines that recommend at least 3 years treatment,” wrote the investigators.
Christina Schwindt, MD, an allergist who practices at Allergy & Asthma Associates of Southern California in Mission Viejo, told Pulmonology Advisor that the GRASS trial has important clinical implications despite missing its primary endpoint. “While this study does not change recommendations to SLIT duration, it does emphasize importance of duration and consequence of early termination of treatment,” she noted. Dr Schwindt was not involved in the study.
- Scadding GW, Calderon MA, Shamji MH, et al; Immune Tolerance Network GRASS Study Team. 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: the GRASS randomized clinical trial. JAMA. 2017;317:615-625. doi: 10.1001/jama.2016.21040
- Cox LS. Sublingual immunotherapy for allergic rhinitis: is 2-Year treatment sufficient for long-term benefit? JAMA. 2017;317:1-3. doi: 10.1001/jama.2017.0128