Total Combined Rhinitis Score Research Articles

Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet (12 SQ-HDM) in children with allergic rhinitis/rhinoconjunctivitis with or without asthma (MT-12): a randomised, double-blind, placebo-controlled, phase III trial

Allergic rhinitis/rhinoconjunctivitis (AR/C) induced by house dust mites (HDM) often begins in childhood and negatively impacts a child's quality of life. The daily burden can be further compounded by comorbid asthma. Allergen immunotherapy is the only available treatment targeting the underlying cause of allergic disease. Efficacy and safety of the SQ HDM sublingual immunotherapy (SLIT)-tablet has been demonstrated in adults and adolescents with HDM AR/C with or without asthma, but data are lacking for younger children. Phase III, randomised, double-blind, placebo-controlled trial in younger children (5-11 years) with HDMAR/C with or without asthma. Eligible subjects were randomised 1:1 to SQ HDM SLIT-tablet or placebo for ∼1year and had free access to AR/C symptom-relieving medications. The primary outcome was the total combined rhinitis score (TCRS) during the final 8 weeks of the treatment period (∼1 year). Secondary outcomes included the rhinitis daily symptom score (DSS) and medication score (DMS), the rhinoconjunctivitis total combined score (TCS), and the Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) score. Efficacy analyses were conducted on the full analysis set (observed cases). Asthma-related outcomes were also explored. The trial was registered on ClinicalTrials.gov: NCT04145219 and EudraCT: 2019-000560-22. A total of 1460 subjects were randomised to SQ HDM SLIT-tablet (n=729) or placebo (n=731). The primary outcome, TCRS, was statistically significantly different for SQ HDM SLIT-tablet (n=693) versus placebo (n=706), with an absolute difference of 1.0 (95% CI: 0.5, 1.4; p<0.0001) corresponding to a relative reduction of 22.0% (95% CI: 12.0, 31.1). Key secondary outcomes (DSS, DMS, TCS, PRQLQ) showed statistically significant reductions in symptoms and medication use, and improved disease-related quality of life for SQ HDM SLIT-tablet versus placebo. Improvements in asthma symptoms and reduced asthma medication use indicated an additional effect of SQ HDM-SLIT tablet versus placebo. The SQ HDM SLIT-tablet showed a higher event rate for treatment-related adverse events (AEs) than placebo. Most events were of mild or moderate severity and few subjects discontinued due to AEs (2.5%). The trial confirmed the efficacy and safety of the SQ HDM SLIT-tablet for treating HDM AR/C in younger children (5-11 years) with or without asthma. The safety profile supports daily self-administration of the SQ HDM SLIT-tablet in children. ALK-Abellό, Hørsholm, Denmark.

Clinical benefits with 300 IR HDM SLIT tablet in Europeans with house dust mite allergic rhinitis: Post hoc analysis of a large phase 3 trial

BackgroundHouse dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. MethodsData from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). ResultsThere were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p < 0.0001): −0.32 (95%CI [-0.46; −0.17]) and −1.28 (95%CI [-1.63; −0.94]), respectively, with relative differences of −20.9% and −21.2%. All post hoc and the rhinoconjunctivitis quality of life endpoints were significantly improved with 300 IR versus placebo. The 300 IR HDM tablet was generally well tolerated. ConclusionThis RCT sub-analysis confirmed the 300 IR HDM SLIT tablet is an effective and safe treatment for European adults and adolescents with HDM-AR with clinically meaningful benefits from the patients' perspective. Trial registrationNCT02443805. Registered on April 29, 2015./EudraCT 2014-004223-46. Registered on September 16, 2015.

Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet in Japanese children.

The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (TO-203, Torii, Japan/ALK, Denmark) treatment has been effective against respiratory allergic diseases in patients aged ≥12years during European, Japanese, and North American trials. This trial was conducted to investigate the efficacy and safety of this treatment in Japanese children (5-17years) with moderate-to-severe HDM allergic rhinitis (AR). In this randomized, double-blind, placebo-controlled trial, 458 Japanese children were randomly assigned to a daily SQ HDM SLIT-tablet [10000 Japanese Allergy Unit (JAU), equivalent to 6 SQ-HDM in Europe and the US] or placebo (1:1) treatment for 1year. Inclusion required an AR symptom score of ≥7 on at least 7days during a 14-day run-in period while symptomatic treatment was withdrawn. The primary endpoint was the total combined rhinitis score (TCRS) comprising AR symptom and medication scores during the last 8weeks of the treatment period. The analysis of primary endpoint demonstrated statistically significant absolute reduction in TCRS of 1.22 with a relative difference of 23% (95% confidence interval, 14% to 31%) in the 10000 JAU compared with placebo. Predefined stratified analyses revealed the same degree of efficacy of 1.11 (P=0.002), 21% (8% to 32%) and 1.36 (P=0.001), 26% (11% to 38%), respectively, in pediatric (5-11years) and adolescent subjects (12-17years). The treatment was well tolerated by both pediatric and adolescent subjects. This trial, for the first time, demonstrated the efficacy and safety of the HDM SLIT-tablet in pediatric patients with moderate-to-severe HDM AR (JapicCTI-152953).

SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration

BackgroundAllergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups. ObjectiveTo evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. MethodsSubgroup (age, sex, race, asthma status, and allergen sensitization) efficacy was assessed using pooled data from 2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138). Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis daily symptom plus medication score) during the last 8 weeks of treatment. Safety in subgroups and local application site reaction onset, duration, and recurrence were evaluated using pooled data from 5 previously described trials of SQ HDM SLIT-tablet (n = 2,923). ResultsSignificant (based on 95% confidence intervals [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was generally similar within subgroups. Approximately 95% of local application site reactions were mild to moderate in severity. Median duration on day 1 of treatment for the most common local application site reactions (throat irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60 minutes; median first day of onset ranged from days 1 to 4 of treatment; median days that reactions recurred ranged from 3 to 12 days. ConclusionTreatment with 12 SQ-HDM consistently improved symptoms and was well tolerated in relevant subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ-HDM were typically mild to moderate and transient.

Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial

BackgroundAllergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo.MethodsFifty-eight AR elderly patients who were monosensitized to house dust mites were individually randomized in comparable numbers to one of two parallel groups with the following interventions: 2 years of perennial AIT using PURETHAL Mites or placebo. The symptoms and medication scores were presented as the AAdSS and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen-specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were monitored. The intent-to-treat population was analysed.ResultsAfter 24 months of AIT, AAdSS significantly decreased from 4.27 ± 1.58 to 1.82 ± 0.71 (p < 0.05). The TCRS was significantly decreased after 2 years of AIT. Serum-specific IgG4 against D. pteronyssinus, D. farinae, Der p1, and Der p2 increased during the AIT trial in the study group. The RQLQ score was significantly improved in patients who received AIT, from 1.86 (95% CI 1.51–1.78) to 1.26 (95% CI 1.09–1.55). Two mild systemic anaphylactic reactions (degree I) were reported after injections in the active group during the AIT therapy.ConclusionThe DBPC trial showed AIT for house dust mite allergens was effective and safe in elderly patients with allergic rhinitis.Trial registrationThis randomized, double-blinded placebo-controlled (DBPC) trial was conducted at one centre (ClinicalTrials.gov no. NCT03209245)

Pooled efficacy and safety data for house dust mite sublingual immunotherapy tablets in adolescents.

House dust mite (HDM) respiratory allergy is a common and burdensome disease in children and adolescents. There are few HDM allergy immunotherapy trials in children with perennial allergic rhinitis. This post hoc analysis used pooled data to evaluate efficacy and safety of the SQ HDM sublingual immunotherapy (SLIT) tablet in adolescents (12-17years). In two double-blind, placebo-controlled trials conducted in North America and Japan, respectively, subjects aged 12+ years with HDM allergic rhinitis were randomized to up to 1year of treatment. The primary end-point in both trials was the average total combined rhinitis score (TCRS) during the last 8weeks of treatment in the active group compared with placebo. Data from subjects aged 12-17years were pooled (N=395). In the pooled adolescent subpopulation, average TCRS improved 22% with 12 SQ HDM vs placebo (absolute treatment difference of 1.04; P<.01). Rhinitis daily symptom score (DSS), conjunctivitis DSS and rhinitis daily medication score (DMS) were also significantly improved vs placebo in the pooled adolescent subpopulation (all P<.05). There were no new safety signals for adolescents. The frequency of adverse events was similar in adolescents and adults with the majority being mild application site-related events. Treatment with 12 SQ HDM appears to be effective and well tolerated in adolescents with HDM allergic rhinitis.

Efficacy and safety of the SQ house dust mite sublingual immunotherapy tablet in Japanese adults and adolescents with house dust mite–induced allergic rhinitis

The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet has been approved in 11 European countries and Japan for patients with HDM-induced respiratory allergic disease. This trial was conducted to confirm the efficacy and safety of the SQ HDM SLIT tablet in Japanese patients with moderate-to-severe HDM-induced allergic rhinitis (AR). The trial was a randomized, double-blind, placebo-controlled trial including 946 Japanese adults and adolescents (12-64years). Subjects were randomly assigned to daily treatment with the SQ HDM SLIT tablet at a dose of 10,000 Japanese allergy units (JAU) or 20,000 JAU or to placebo (1:1:1). The primary end point was the total combined rhinitis score (TCRS), which is composed of AR symptom and medication scores during the efficacy evaluation period. Symptom and medication scores of AR and conjunctivitis, rhinitis quality of life, and symptom-free and symptom-severe days were evaluated as secondary end points. Analysis of the primary end point demonstrated statistically significant reductions in TCRSs of 1.15 (22%, P<.001) in the 10,000-JAU group and 0.99 (19%, P<.001) in the 20,000-JAU group compared with the placebo group. The statistically significant treatment effect was evident from 12weeks of treatment onward. All secondary end points, except AR medication score, were statistically significant in favor of active treatment compared with placebo. Post hoc analysis of TCRSs in adolescents showed the same efficacy as in adults (P<.05). The treatment was well tolerated by both adults and adolescents. The trial confirmed the efficacy and safety profile of the SQ HDM SLIT tablet in Japanese adult and adolescent patients with moderate-to-severe HDM-induced AR. These data support the robust efficacy and safety profile of previously reported European data.

Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial

The house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (MK-8237; Merck & Co, Kenilworth, NJ/ALK-Abelló, Hørsholm, Denmark) has demonstrated beneficial effects on allergic rhinoconjunctivitis and asthma outcomes in European trials. This is the first trial to assess the efficacy/safety of HDM SLIT-tablets in North American subjects with HDM-induced allergic rhinitis with or without conjunctivitis (AR/C). In this double-blind, multicenter trial (NCT01700192) 1482 subjects (aged ≥12years) with HDM-induced AR/C with or without asthma were randomized to a daily SQ HDM SLIT-tablet (12 SQ-HDM dose) or placebo for up to approximately 52weeks. Arhinitis daily symptom score (DSS; 4 nasal symptoms, maximum score=12) of 6 or greater, or 5 or greater with 1 symptom being severe, on 5 of 7 consecutive days before randomization was required. The primary end point was the average total combined rhinitis score, which was defined as the rhinitis DSS plus rhinitis daily medication score (DMS), during the last 8 treatment weeks. Treatment with 12 SQ-HDM improved the total combined rhinitis score by 17% (95% CI, 10% to 25%) versus placebo. Improvements versus placebo in the secondary end points of average rhinitis DSS, rhinitis DMS, total combined rhinoconjunctivitis score, and visual analog scale-assessed AR/Csymptoms were 16%, 18%, 17%, and 16%, respectively. All nominal P values were less than .001 versus placebo, except rhinitis DMS (P=0.15). No treatment-related adverse events meeting the International Council on Harmonizationdefinition of a serious adverse event were reported; 1 nonserious treatment-related systemic allergic reaction occurred (assessed as moderate intensity) at first administration under medical supervision and was treated with epinephrine. In the first North American trial of use of a SLIT-tablet for HDM allergy, 12 SQ-HDM was well tolerated and improved HDM-induced rhinitis symptoms in adults and adolescents.

Effective treatment of house dust mite–induced allergic rhinitis with 2 doses of the SQ HDM SLIT-tablet: Results from a randomized, double-blind, placebo-controlled phase III trial

The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease. This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR). The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score. Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 (P=.002) and 1.22 (P=.001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated. The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14weeks of treatment onward.

SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms

BackgroundHouse dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. ObjectiveTo investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease and report the AR results. MethodsSix hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). ResultsIn the subgroup, the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was −0.78 (95% confidence interval −1.47 to −0.07, relative difference 28.8%, P = .0357). Furthermore, a significant difference was found for the total score of the Rhinitis Quality of Life Questionnaire with Standardized Activities RQLQ(S) and for the individual domains: activities, sleep, non-nose and non-eye symptoms, and nasal symptoms. For the TCRS and Rhinitis Quality of Life Questionnaire score, a dose response was seen, with numerically lower, nonsignificant differences for 1 and 3 SQ-HDM. The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups. No safety concerns were observed. ConclusionEfficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Questionnaire score in subjects with AR present at baseline. The treatment was well tolerated. Trial RegistrationEudraCT, no 2006-001795-20; ClinicalTrials.gov, identifier NCT00389363.