Pollen Sublingual Immunotherapy Tablets Research Articles

Efficacy of Japanese cedar pollen sublingual immunotherapy tablets for Japanese cypress pollinosis.

We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial (trial no. 206-2-1) that covered 5 pollen dispersal seasons from 2015 to 2019. Our aim was to perform post hoc analysis of the 206-2-1 trial data to evaluate the efficacy of JC pollen SLIT tablets for patients with rhinitis induced by pollen from Japanese cypress (JCY), a related Cupressaceae species that has a pollen dispersal season overlapping with that of JC. Data were analyzed for 240 patients who received placebo during the first pollen dispersal season in 2015, were then rerandomized to receive JC SLIT tablets (the PA group) or placebo (the PP group) for 18 months (the 2016 and 2017 dispersal seasons), and were observed untreated for 2 years (the 2018 and 2019 dispersal seasons). The PA and PP groups were assigned to "high" and "low" subgroups if their rhinitis symptoms were exacerbated/did not change or decreased, respectively, during the peak JCY pollen dispersal period in 2015. The mean total nasal symptom and medication scores and other outcomes were compared for the high-PP, high-PA, low-PP, and low-PA groups during the 2016 to 2019 peak JCY pollen dispersal periods. The mean total nasal symptom and medication scores were significantly lower for the high-PA and low-PA groups than for the corresponding PP groups over the 4 years of treatment and observation. JCY pollen-specific IgE levels increased in both PA groups. JC pollen SLIT tablets effectively suppressed JCY pollinosis symptoms, supporting the clinical relevance of immunologic cross-reactivity between JC and JCY allergens.

Disease-Modifying Effect of Japanese Cedar Pollen Sublingual Immunotherapy Tablets

Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis. To assess the disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up. A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimalactive dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation. The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site. JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation.

Efficacy of sublingual immunotherapy tablets in dust mite and pollen allergy.

The latest evidence on the mechanisms, efficacy, and safety of sublingual immunotherapy (SLIT) was reviewed. Interleukin (IL) 35 and IL-35-producing regulatory T cells were assessed as new biomarkers for SLIT responsiveness. A detailed analysis of clinical studies, including timothy grass pollen, 5-grass pollen, ragweed, and house-dust mite SLIT tablets, was provided, including a comparative analysis of efficacy and safety of SLIT versus subcutaneous immunotherapy.

Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet

BackgroundThere have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. MethodsThis was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. ResultsThe percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. ConclusionsDual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.

Grass pollen sublingual immunotherapy tablets provide long-term relief of grass pollen-associated allergic rhinitis and reduce the risk of asthma: findings from a retrospective, real-world database subanalysis

ABSTRACTBackground: We assessed real-world, long-term effectiveness of two marketed sublingual immunotherapy (SLIT) tablets for allergic rhinitis (AR), and their impact on allergic asthma (AA) onset/progression.Methods: Retrospective, longitudinal German prescription database subanalysis of AR patients receiving 5- or 1-grass pollen SLIT tablets (n = 1,466/1,385), versus patients not using allergy immunotherapy (AIT) (n = 71,275).Primary endpoint: change over time in AR symptomatic medication prescriptions after treatment cessation; secondary endpoints: new asthma onset, and change over time in asthma medication prescriptions during treatment/follow-up periods.Results: Mean number of AR medication prescriptions was significantly decreased during follow-up (of up to 6 years) with both SLIT tablets versus the non-AIT group (p < 0.001).Over the full-analysis period, proportions of patients with new-onset asthma were 8.8% (odds ratio: 0.676, p = 0.011), 10.3% (odds ratio: 0.720, p = 0.060) and 11.6% in the 5- and 1-grass pollen SLIT tablet and non-AIT groups, respectively.For all treatment-analysis periods, both SLIT tablet groups were associated with fewer asthma medication prescriptions versus non-AIT controls.Conclusions: These findings confirm the real-world benefits of 5- and 1-grass-pollen SLIT tablets in slower AR progression, reduced risk of new asthma onset in the non-asthmatic population, and slower asthma progression in the asthmatic population.

Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

BackgroundAllergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long‐term efficacy. However, there are few real‐life data on the progression of AR and/or AA in patients receiving AIT.ObjectivesTo assess the real‐world, long‐term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.MethodsIn a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.ResultsAfter applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non‐AIT group (P<.001). Asthma onset was less frequent in SLIT tablet group than in non‐AIT group (odds ratio: 0.696, P=.002), and time to asthma was significantly longer (hazard ratio: 0.523; P=.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pretreatment period) in the SLIT tablet group vs the non‐AIT group (P=.004).ConclusionsReal‐world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression.

300IR 5-Grass pollen sublingual tablet offers relief from nasal symptoms in patients with allergic rhinitis.

300IR 5-grass pollen sublingual immunotherapy tablets have been approved for the treatment of allergic rhinitis (AR) with or without conjunctivitis in adults and children >5 years with grass pollen allergy. This study was designed to review data on nasal symptoms with 300IR 5-grass pollen sublingual tablets in adults and children. We reviewed data from four double-blind, placebo-controlled, randomized clinical trials. Two groups of patients who received a daily dose of either placebo or 300IR 5-grass pollen sublingual tablets starting 4 months before the expected start of the pollen season and continuing through the season were compared (analysis of covariance) for scores of sneezing, rhinorrhea, nasal pruritus, nasal congestion, total nasal symptom score (TNSS), and adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores. Data for 266 children (one pediatric trial) and 1036 adults (three trials) were analyzed. Compared with the placebo groups, mean TNSS in the 300IR groups was lower by 22% in children and 19-36% in adults. Among the four nasal symptoms, the lowest scores relative to placebo were for nasal congestion in children (31%) and adults (43%). Mean adult RQLQ scores were 21-31% lower in the 300IR group than in the placebo group. Allergen immunotherapy with 300IR 5-grass pollen sublingual tablets was consistently associated with AR symptom relief in adults and children and provided a clinically meaningful improvement in quality of life.

Re: The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

Summary Background In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. Objective To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. Methods To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSSd) is defined as the value of RTSSd or AdSSd−1, whichever is higher. The AdSS on the following day (AdSSd+1) is defined as the value of RTSSd+1 or AdSSd, whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). Results The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. Conclusion and Clinical Relevance The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials. Cite this as: J.-M. Grouin, E. Vicaut, S. Jean-Alphonse, P. Demoly, U. Wahn, A. Didier, O. de Beaumont, A. Montagut, M. Le Gall and P. Devillier, Clinical & Experimental Allergy, 2011 (41) 1282–1288.

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.

The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSS(d)) is defined as the value of RTSS(d) or AdSS(d-1), whichever is higher. The AdSS on the following day (AdSS(d+1)) is defined as the value of RTSS(d+1) or AdSS(d), whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials.

Efficacy and safety of 5‐grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis

SummaryBackgroundThe optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season.ObjectiveThe aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic to grass pollen.MethodsDifferent subgroups could be identified regarding comorbidities (with or without asthma during the grass-pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre-treatment assessment: Group 1=high specific IgE; Group 2=high symptom scores; Group 3=high skin sensitivity; Group 4=any of Group 1, 2 or 3.ResultsAsthma and sensitization status were not significant covariates as the average Rhinoconjunctivitis Total Symptom Score (RTSS) was identical for patients with and without grass-pollen asthma, as well as for mono- and polysensitized patients. Across the four subgroups, average RTSSs (± SD) for the optimal dosage (300 IR) were 3.91 ± 3.16, 3.83 ± 3.14, 2.55 ± 2.13 and 3.61 ± 2.97, for subgroups 1, 2, 3 and 4, respectively. ancova showed that in Group 1 average RTSS did not differ significantly with different doses of SLIT. In Groups 2, 3 and 4, doses of 300 IR and 500 IR were significantly more effective than 100 IR and placebo (P0.035). All doses of SLIT administered in this study can be considered safe in the patients investigated.ConclusionsThe risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma.