[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH CEDAR POLLEN IN A YEAR OF MASSIVE CEDAR POLLEN DISPERSAL AND ITS EFFECT ON JAPANESE CYPRESS POLLINOSIS].

BACKGROUND: We investigated the effect of sublingual immunotherapy (SLIT) on Japanese cedar and cypress pollinosis in a mass scattering year of cedar pollen (total counts: 12353 grains/cm2, approximately four times the average). METHODS: SLIT patients of 84 in the first year, 107 in the second year and 67 in the third year treated with Cedarcure® were included. During the 2023 cedar and cypress pollen dispersal season, nasal and eye symptoms and general symptoms were examined using a visual analog scale (VAS). RESULTS: The VAS during the cedar season significantly decreased to improve with the number of years of SLIT, but the VAS during the cypress period slightly increased. A questionnaire survey before SLIT revealed that only 0.9% to 3.6% of patients had strong cypress symptoms. However, sneezing (p＜0.01), rhinorrhea, itchy eyes and total symptoms (p＜0.05) in the third year of SLIT were significantly stronger during the cypress period than during the cedar period. The VAS of total symptoms during the Japanese cedar pollen season were not affected by the pollen count, and the cure rate was affected by SLIT in the third year. CONCLUSION: The clinical efficacy of cedar SLIT on cedar pollinosis was high even in a mass scattering year, and the effect increased with the number of years of treatment. On the other hand, it was shown that the clinical efficacy on cypress pollinosis was insufficient.

[CLINICAL EFFICASY OF HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY WITH MITICURE® TABLETS IN 115 PAITENTS FOR 3 YEARS].

We reported the results of three years of house dust mite sublingual immunotherapy with Miticure® tablets. METHODS: Subjects of 115 cases (63 males, median 12.9 years old, 74 children under 15 years old) were evaluated with Japanese Rhino-conjunctivitis Quality of Life Questionnaire No1 (JRQLQ No1) and visual analog scale (VAS) of 100mm length for rhino-ocular and general symptoms. Annual survey was conducted for three years. RESULTS: Symptoms in all items of 1 to 3 years later by JRQLQ No1 and VAS were significantly improved (p<0.01). There was no difference from 1 year to 3 years later. The VAS value for total symptoms decreased from 41 (18-70) mm before treatment to 10 (4-40) mm after 1 year and 10 (3-30) mm after 3 years (median (IQR)). Concomitant medications used in all patients at the start of treatment were not needed in 60.8% after 1 year and 65.2% after 3 years. After 3 years, 16.5% of the patients were completely cured with no concomitant medication and had a symptom score of 0, and 53.0% were in remission with a score of 1 or less. There was no difference in all items between children and adults, and symptoms improved equally. CONCLUSION: The efficacy of house dust mite sublingual immunotherapy from 1 to 3 years was demonstrated.

[ENHANCED CLINICAL EFFECTS OF CEDARCURE® TABLETS OF SUBLINGUAL IMMUNOTHERAPY OVER THE YEARS OF TREATMENT AND THE IMPACT OF OUTCOME BY COMBINED USE OF MITE SUBLINGUAL IMMUNOTHERAPY (DUAL SLIT) FOR JAPANESE CEDAR POLLINOSIS].

BACKGROUND: We examined the clinical effects of Cedarcure® tablets for sublingual immunotherapy (SLIT), and examined the enhancement of the effects over the years of treatment. METHODS: The subjects were 358 patients who treated with SLIT (126 of third year of treatment, 102 of second year, 130 of first year) in a single clinic. The clinical efficacy was evaluated with visual analog scale (VAS) of nose, eye and total symptoms during the peak season of moderate amount of pollen dispersal (2485 grains/cm2/season) in 2022. Concomitant medication scores were calculated by Japanese guidelines. Because many cases of combined use of mite SLIT (dual SLIT) were included in the subjects, we compared cedar SLIT alone and dual SLIT as a secondary analysis. RESULTS: Clinical efficacy improved with the years of treatment, and all assessments of VAS in the 3rd year were significantly better than in the 1st year of treatment (p<0.01). The third year was better with sneezing and nasal discharge than the 2nd year, and the 2nd year was better with itchy eyes than the 1st year (p<0.05). Drug scores were also lower in the 3rd and 2nd years than in the 1st year (p<0.05). Additional mite SLIT did not affect the results. CONCLUSION: Cedarcure® showed enhancement of the effects over the years of treatment by the analysis up to the third year. Both Cedar SLIT alone and Dual SLIT showed similar efficacy on cedar pollinosis.

[COMPARISON OF CLINICAL EFFICACY AND SAFETY BETWEEN CHILDREN AND ADULTS BEFORE AND 1 YEAR AFTER MITE SUBLINGUAL IMMUNOTHERAPY FOR PERENNIAL ALLERGIC RHINITIS].

BACKGROUND: We studied clinical efficacy and safety after 1 year of mite sublingual immunotherapy (SLIT) for perennial allergic rhinitis in children, compared with adults. METHODS: We compared 121 children under 15 yeas old (81 male, aged 5-14 years, a median of 12 years) and 77 adults (36 male, aged 15-65 years, a median of 26 years) treated with mite SLIT tablet (10000 Japanese Allergy Unit). The clinical efficacy before and 1 year after SLIT was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire (JRQLQ No1) and visual analog scale (VAS). Combined medication was also compared. Adverse events of SLIT were checked at every visit. RESULTS: All items of JRQLQ No1 scores and VAS after 1 year of mite SLIT, except eye symptoms in adults by JRQLQ No1, were significantly improved in both children and adults. Comparing children and adults, there were no differences in symptoms before and after 1 year. Combined medication score showed a similar result. Adverse events were observed in 57.9% of children and 58.4% of adults, but there were no serious adverse reactions. CONCLUSION: There was no difference between children and adults in efficacy and safety of mite SLIT, and both group showed significant improvement of symptoms.

[EFFICACY AND SAFETY OF PEDIATRIC SUBLINGUAL IMMMUNOTHERAPY WITH CEDARCURE® IN CLINICAL PRACTICE FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP SEASON].

BACKGROUND: We studied clinical efficacy and safety of pediatric sublingual immunotherapy of cedar pollinosis in the first follow-up year, compared with adult cases or untreated cases. METHODS: We compared 103 pediatrics under 15 yeas old (age, 10.8±2.6 years; male-to-female ratio, 68;35) and 89 adults (age, 38.9±12.5 years; male-to-female ratio, 34;55) treated with Cidarcure®, and untreated 299 patients (age, 31.3±16.0; male-to-female ratio, 144;155). The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS) during the peak season of moderate amount of pollen dispersal (3582 grains/cm2/season) in 2020. Adverse events of sublingual immunotherapy were also checked at every visits. RESULTS: All patients in both pediatric and adult group successfully maintained the highest dose of 5000JAU as planned. Pediatrics compared with adults showed slightly better effects in all the assessments, but they were not significant. Both pediatrics and adults of sublingual immunotherapy showed significant better effects in all the assessments compared with untreated group. Percentage of total cases of adverse events in pediatric group was low, but it was not significant. Percentage of pruritus of ear and throat was significantly low in pediatric group. CONCLUSION: Pediatric sublingual immunotherapy for cedar pollinosis was treated in safe, and reduced symptoms as well as the effects of adults.

[CLINICAL EFFICACY OF 69 PATIENTS WITH JAPANESE CEDAR POLLINOSIS TREATED BY SUBLINGUAL IMMUNOTHERAPY WITH CEDARCURE® IN THE FIRST FOLLOW-UP YEAR].

BACKGROUND: Cedarcure® for sublingual immunotherapy of cedar pollinosis was purchased in 2018. We studied clinical efficacy of Cedarcure® in the first year. METHODS: We compared 69 patients treated with Cedarcure® (age, 18.0±13.5 years; male-to-female ratio, 40;29) and a control group of 97 patients treated with Cedartolen® (age, 29.8±16.2 years; male-to-female ratio, 44;53) during the peak season of large amount of pollen dispersal (10933 grains/cm2/season) in 2019. The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS). RESULTS: All the assessments except nasal congestion were slightly better in Cedarcure® group, but they were not significant. There was no difference of concomitant medication in both groups. Because insurance coverage of Cedartolen® is for patients over 12 years old in Japan, the efficacy in Cedarcure® group enhanced better in all assessments if comparing the patients of over 12 years old. Percentage of adverse events was even in both over and under 12 years old. CONCLUSION: Cedarcure® was treated in safe, and reduced symptoms as well as Cedartolen®.

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN A LARGE AMOUNT OF POLLEN DISPARSAL AND IT'S IMPACT OF TREATMENT YEAR].

BACKGROUND: It past 4 years in 2018 after the first treatment of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. The purpose of this study is to clear the clinical efficacy of SLIT in a large amount of pollen dispersal in 2018 (total 5041 grain). METHODS: The subjects were 270 SLIT (83 forth year of treatment, 72 third year, 48 second year, 67 first year), 320 primary pharmacotherapy that started therapies before pollen dispersal, and 424 untreated. The clinical efficacy was evaluated with symptom scores of Japanese rhinoconjuctivitis quality of life questionnaire No1, medication scores and combined total nasal symptom-medication scores, and visual analog scale of nose, eye and total symptoms. RESULTS: Each SLIT was significantly better than untreated in all assessments, and better than primary pharmacotherapy in assessments of total symptom. SLITs of third and forth year of treatment were also better than primary pharmacotherapy in nasal symptoms. SLIT patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 41.0%, 31.9%, 18.8%, 20.9% in the order from the fourth year to the first year. Of them, patients with score 0 occupied 12.0%, 12.5%, 4.2%, 4.5%, in order. There was no patient who needs treatments for adverse events. CONCLUSION: SLIT was significantly effective compared with primary pharmacotherapy or untreated group in a large amount of pollen dispersal. It was better to treat at least for 4 years.

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN THE THIRD TREATED YEAR WITH JAPANESE CEDAR POLLINOSIS IN 2017].

It past 3 years in 2017 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). We reported the clinical efficacy of SLIT in the first and the second treated year. PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the third treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We compared the clinical efficacy in 2017, of 112 SLIT in the third treated year with 38 SCIT, 364 primary pharmacotherapy that started therapies before pollen dispersal, 254 pharmacotherapy that started therapies after pollen disposal, or 333 non-treatment. The clinical efficacy was evaluated with symptom scores, total nasal symptom scores and combined total nasal symptom-medication scores (TNSMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 9 and 24% of total SLIT, respectively. CONCLUSION: SLIT in the third treated year showed good clinical efficacy in reducing symptoms and TNSMS of JCP, and in improving QOL. SLIT was significantly effective compared with other pharmacotherapies.

Enhanced Clinical Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis in the Second Year of Treatment.

Sublingual immunotherapy (SLIT) is thought to have enhanced efficacy in the second year of treatment. We studied treatment efficacy in both the first and the second years of treatment (2015 and 2016, respectively) in patients who began SLIT in 2014. Methods: We compared 132 patients who underwent SLIT (age, 41.8 ± 17.5 years; male-to-female ratio, 75: 57) and a control group of 56 patients who underwent primary pharmacotherapy (age, 44.9 ± 13.5 years; male-to-female ratio, 25: 31). The study was performed during the peak pollen seasons of 2015 and 2016. Pollen dispersal was similar in 2015 and 2016 (2,509 grains/cm2 and 3,505 grains/cm2, respectively). The clinical efficacy of SLIT was evaluated by assessing nasal and eye symptoms and total symptoms with symptom scores and combined symptom-medication scores, visual analog scale scores, and quality of life (QOL) scores according to the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No. 1). QOL was also evaluated with JRQLQ No. 1. The first endpoint was enhanced efficacy of SLIT in the second year compared with that in the first year. Results: With respect to nasal and eye symptoms, the assessments in the primary pharmacotherapy group were unchanged in the second year; however, most of these assessments in the SLIT group demonstrated significantly enhanced efficacy of SLIT in the second year. In QOL of SLIT, only 2 of 17 showed significantly enhanced efficacy of SLIT in the second year. Conclusion: SLIT shows enhanced efficacy in the second year.

CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN THE SECOND TREATED YEAR FOR 133 PATIENTS WITH JAPANESE CEDAR POLLINOSIS IN 2016.

It past 2 years in 2016 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the second treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We started SLIT at our clinic in October-December, 2014. We compared the clinical efficacy in 2016, of 133 SLIT with 46 SCIT, 351 primary pharmacotherapy that started therapies before pollen dispersal, 221 pharmacotherapy that started therapies after pollen disposal, or 337 non-treatment. The clinical efficacy was evaluated with symptom scores and combined symptom-medication scores (SMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Fourteen cases by unknown reasons and 3 cases by inevitable reasons were dropped out for 2 years. Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 or 1 point without any rescue drugs, accounted for 26.3% of total SLIT. CONCLUSION: SLIT in the second treated year showed good clinical efficacy in reducing symptoms and SMS of JCP, and in improving QOL. SLIT was significantly effective compaired with other pharmacotherapies.

Adherence and Clinical Outcome of Sublingual Immunotherapy for Japanese Cedar Pollinosis.

Sublingual immunotherapy (SLIT) for Japanese cedar pollinosis is known to be effective. However, better SLIT adherence is needed to improve its safety and efficacy. 　Purpose: The purpose of this study was to evaluate SLIT adherence and its influence on clinical outcome. 　Methods: We conducted a detailed survey of 132 patients who have been receiving SLIT for 2 years on adherence at each visit using both questionnaires and direct calculation from prescription. Questionnaires on total symptoms using the visual analog scale (VAS), face scale, and total nasal symptom medication score (TNSMS) were obtained at the peak season for Japanese cedar pollinosis. 　Results: Good adherence by prescription for 2 years was observed in 83.1% ± 11.7% of patients. The adherence in the second year (80.8% ± 13.6%) was lower than that in the first year (88.5% ± 9.8%). However, adherence by questionnaire was 13.5% higher than that by prescription. VAS of total symptoms and adherence did not correlate; however, evaluations by VAS, face scale, and TNSMS were significantly improved if the adherence cut-off value was set to 70% or 75%. 　Conclusion: Our results suggest that SLIT adherence for Japanese cedar pollinosis is high and adequate adherence is required for better efficacy.

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP YEAR].

UNLABELLED: The first drug of sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP) was purchased in 2014.   PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy.   METHODS: We started SLIT at our clinic in October-December, 2014. We compared the clinical efficacy of 191 SLIT with 48 SCIT, 191 primary pharmacotherapy that started therapies before pollen dispersal, 141 pharmacotherapy that started therapies after pollen disposal, or 169 non-treatment in the first follow-up year. The clinical efficacy was evaluated with quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1), symptoms of nose and eye by visual analog scale (VAS), symptom scores and combined symptom-medication scores (SMS).   RESULTS: Mild adverse events (AEs) were observed in many cases, but no patient was discontinued by AEs in SLIT patients. Five cases by unknown reasons and 3 cases by inevitable reasons were dropped out before pollen. Adherence of SLIT was 89±12%. SCIT was better than SLIT in most assessments, but not significant. Both SCIT and SLIT were significantly better than other pharmacotherapy. Patients, whose symptom scores of nose and eye were 0 or 1 point without any rescue drugs, accounted for 16.8% of total SLIT in the first follow-up year.   CONCLUSION: SCIT was slightly better than SLIT in reducing symptoms and SMS of JCP, and in improving QOL. However, the differences were not significant. SLIT was significantly effective than other pharmacotherapies.

[Adverse Events of Sublingual Immunotherapy in 207 Patients with Japanese Cedar Pollinosis].

UNLABELLED: Sublingual immunotherapy (SLIT) for Japanese cedar pollinosis is effective, however, caution must be exercised against allergen-specific adverse events (AEs) during SLIT. PURPOSE: The purpose of this study was to clarify the AEs of SLIT in a large cohort of patients with Japanese cedar pollinosis. METHODS: We conducted a detailed survey, by both questionnaires and direct interviews, of 207 patients receiving SLIT at our clinic. RESULTS: Eighty-four of the 207 patients (40.5%) developed AEs, with AEs involving the oral cavity and throat being the most common (56 patients; 27.1%). Sixteen patients (7.9%) had local mucosal swelling, but the swelling resolved in all the cases. Other allergen-induced symptoms such as nasal symptoms (29 events, 14.0%), eye symptoms (14 events, 6.8%) and ear symptoms (20 events, 9.7%) were also recognized. All the AEs were minor, and discontinuation of SLIT was not necessitated in any of the patients because of AEs. There were 52 AEs (25.0%) in the up-dose phase and 61 AEs (29.3%) in the maintenance phase. However, only 4 of the 161 patients (2.5%) developed AEs during the pollen season. Most AEs developing during the maintenance phase occurred in the first few weeks. In 60% of the cases, the AEs disappeared within 2 weeks, and in 6.0% (5 events), they persisted for longer than 2 months. There were no age-or sex-related differences in the prevalence of cedar pollen-specific IgE, or in the adherence to the treatment. CONCLUSION: AEs in SLIT were shown in many patients, however, the severity of AEs was mild and no events interfered SLIT.

IL-33-activated dendritic cells induce an atypical TH2-type response.

BACKGROUND: IL-33, a recently discovered IL-1 family cytokine, is implicated in the development of T(H)2-type responses in vivo. However, the cellular targets for IL-33 are poorly understood. OBJECTIVE: We tested the hypotheses that dendritic cells (DCs) respond to IL-33 and that IL-33-activated DCs prime naive CD4(+) T cells to produce T(H)2-type cytokines. METHODS: Dendritic cells were derived from mouse bone marrow, and their expression of the IL-33 receptor, ST2, was examined by fluorescence-activated cell sorting and real-time RT-PCR. The DCs' responses to IL-33 were examined by fluorescence-activated cell sorting (MHC-II and CD86 expression) and by ELISA (IL-6 and IL-12 production). The ability of IL-33-activated DCs to prime naive T cells was assessed by coculture with isolated CD4(+) T cells and by measuring cytokines in the supernatants. RESULTS: ST2 mRNA was detectable in highly purified DCs. ST2 protein was abundant within DCs, but was barely detectable on their cell surfaces. Incubation of DCs with IL-33 increased their expression of MHC-II and CD86 and production of IL-6, but IL-12 was not produced. Anti-ST2 antibody inhibited IL-6 production from IL-33-activated DCs by approximately 60%; anti-ST2 did not affect IL-6 production from LPS-activated DCs. When incubated with naive CD4(+) T cells alone, IL-33 failed to stimulate cytokine production. In contrast, naive CD4(+) T cells incubated with IL-33-activated DCs showed robust production of IL-5 and IL-13, but IL-4 and IFN-gamma were undetectable. CONCLUSION: Dendritic cells respond directly to IL-33 through ST2. The IL-33 and DC interaction may represent a new pathway to initiate T(H)2-type immune responses.