Subcutaneous allergen immunotherapy in the treatment of allergic respiratory disease.

Subcutaneous immunotherapy is recognized as a cornerstone in the management of allergic respiratory disease in patients who are properly characterized with allergy and with allergic rhinoconjunctivis and/or well-controlled asthma, and who are willing to adhere to the rigorous treatment program. A key tenet is that it affords the opportunity to effect long-term clinical remission through its disease-modifying properties. Furthermore, it has the potential to prevent the progression of allergic rhinitis to asthma, prevent new allergen sensitivities, and improve a patient's quality of life.

A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-controlled, randomized phase III clinical trial.

BACKGROUND: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. OBJECTIVE: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate to severe HDM-induced allergic rhinitis. METHODS: In a phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period. RESULTS: A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P < .0001) than in the placebo group (4.35), with a relative least squares mean difference of -16.9% (95% CI, -24.0% to -9.2%). All prespecified secondary end points were consistently improved in the 300 IR group, relative to placebo. The 300 IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300 IR group and 14.9% in the placebo group. CONCLUSIONS: The 300 IR sublingual HDM tablet is an effective, safe treatment for HDM-induced allergic rhinitis.

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.

Mind the gaps: Clinical trial concepts to address unanswered questions in aeroallergen immunotherapy-An NIAID/AHRQ Workshop.

The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT; (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized; (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.

Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses.

BACKGROUND: Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. OBJECTIVE: We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 µg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. RESULTS: In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. CONCLUSIONS: Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional benefit of long-term efficacy.

Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis.

BACKGROUND: Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in North America. OBJECTIVE: To determine the efficacy and tolerability of standardized glycerinated short ragweed sublingual allergen immunotherapy liquid (RW-SAIL) extract in subjects with ragweed-related ARC. METHODS: This phase 3, randomized, placebo-controlled trial was conducted in North America. Subjects (age range, 18-55 years) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed. Subjects self-administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season. The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores (TCS). RESULTS: During the entire season, there was a 43% decrease in TCS in subjects treated with RW-SAIL compared with placebo. Similar decreases were observed in TCS between the 2 groups during peak season (42%) and in daily symptom scores during the entire (42%) and peak (41%) seasons. The occurrence of adverse events was similar between the treatment groups; most were mild in severity. Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited. No anaphylaxis occurred. CONCLUSIONS: This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual standardized ragweed allergen immunotherapy liquid extract for the treatment of ARC.

Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial.

BACKGROUND: In North America, few studies have evaluated sublingual immunotherapy for allergic rhinitis with or without conjunctivitis (AR/C); pediatric data are sparse. The authors report findings from the largest published immunotherapy trial yet conducted in adults and children. OBJECTIVE: To evaluate grass sublingual immunotherapy tablet (MK-7243) treatment in subjects with AR/C. METHODS: North American subjects (5-65 years old) with grass allergy were randomized 1:1 to once-daily MK-7243 (2,800 BAU Phleum pratense) or placebo. The first dose was given at the investigator's office; subsequent doses were self-administered at home. The primary end point was total combined score (TCS; rhinoconjunctivitis daily symptom score [DSS] plus daily medication score [DMS]) over the entire grass pollen season (GPS). Key secondary end points included entire-season DSS, DMS, peak-season TCS, and rhinoconjunctivitis quality-of-life questionnaire scores. Safety outcomes included adverse events (AEs). RESULTS: One thousand five hundred one subjects were randomized (85% polysensitized, 25% had asthma). MK-7243 yielded improvements vs placebo of 23% in entire-season TCS (median difference -0.98, P < .001), 29% in peak-season TCS (median difference -1.33, P < .001), 20% in entire-season DSS (median difference -0.64, P = .001), 35% in entire-season DMS (mean difference -0.48, P < .001), and 12% in peak-season rhinoconjunctivitis quality-of-life questionnaire (median difference -0.13, P = .027). Efficacy between children and adults was similar. Most AEs were transient local application-site reactions, with no serious treatment-related AEs or anaphylactic shock. Three subjects (1 placebo, 2 MK-7243) had moderate systemic allergic reactions. CONCLUSION: MK-7243 was effective in polysensitized grass-allergic North American children and adults with AR/C in this large trial, confirming previous research.

Safety and tolerability of a short ragweed sublingual immunotherapy tablet.

BACKGROUND: MK-3641 is a short ragweed sublingual tablet under investigation for immunotherapy of ragweed pollen-induced allergic rhinitis. OBJECTIVE: To characterize the safety and tolerability of a ragweed sublingual tablet (Merck/ALK-Abelló) in ragweed-allergic adults with or without conjunctivitis. METHODS: Data from 4 randomized, double-blinded, placebo-controlled trials of MK-3641 (2 28-day and 2 52-week trials) were evaluated. Pooled analyses examined short-term safety over 28 days from all 4 trials and long-term safety from the 52-week trials. RESULTS: Across all studies, 757, 198, 454, and 1,058 subjects were randomized to placebo or 1.5, 6, or 12 Amb a 1-U of MK-3641, respectively. Treatment-related adverse events were more frequent in the 6- and 12-Amb a 1-U MK-3641 groups than in the placebo group and were primarily local application-site reactions occurring in the first few days of treatment. There was no treatment-associated loss of asthma control or worsening of asthma associated with treatment. No swellings led to airway obstruction or respiratory compromise. No treatment-related anaphylactic shock, life-threatening, or serious treatment-related adverse events were reported for any MK-3641 dose. Of the 1,707 MK-3641-treated subjects, 1 systemic (anaphylactic) reaction was reported (0.06%). The 52-week long-term assessment was generally similar to the safety profile based on the 28-day assessment. CONCLUSION: MK-3641 doses up to and including 12 Amb a 1-U were well tolerated, with no unexpected safety findings. Sublingual immunotherapy risks such as worsening asthma or airway swellings that could cause airway obstruction were not observed. Systemic reactions and use of epinephrine were uncommon. In these studies, after the first dose was administered in a health care setting, self-administration was well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01469182, NCT00783198, NCT00770315, and NCT00978029.

Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults.

BACKGROUND: In North America and Europe, millions of patients experience symptoms of allergic rhinitis with or without conjunctivitis (AR/C) on exposure to ragweed pollen. The disease burden can be significant, with most patients relying on symptomatic medications without disease-modifying potential. However, novel sublingual immunomodulatory treatment options may potentially play an important role if efficacy and side effect profiles allow the convenience of self-administration. OBJECTIVES: This study evaluated an allergy immunotherapy tablet (AIT; SCH 39641/MK-3641) for treatment of ragweed-induced AR/C in the first large randomized, double-blind multinational trial of this therapeutic modality for ragweed allergy. METHODS: Adults (n = 784) with short ragweed-induced AR/C were randomly assigned to approximately 52 weeks of daily self-administered ragweed AIT of 1.5, 6, or 12 units of Ambrosia artemisiifolia major allergen 1 (Amb a 1-U) or placebo. Subjects could use as-needed allergy rescue medication. Symptoms and medications were recorded daily. The primary efficacy end point was total combined daily symptom/medication score (TCS) during peak ragweed season. Safety was monitored through adverse event diaries maintained through study duration. RESULTS: During peak ragweed season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 9% (-0.76; P = .22), 19% (-1.58; P = .01), and 24% (-2.04; P = .002) compared with placebo. During the entire season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 12% (-0.88; P = .09), 18% (-1.28; P = .01), and 27% (-1.92; P < .001) compared with placebo. Treatment was well tolerated; no systemic allergic reactions occurred. CONCLUSIONS: In this trial, ragweed AIT of 12 Amb a 1-U was effective and tolerable with a safety profile that permitted daily self-administration of ragweed allergen immunotherapy.

Allergen Immunotherapy: The Evidence Supporting the Efficacy and Safety of Subcutaneous Immunotherapy and Sublingual Forms of Immunotherapy for Allergic Rhinitis/Conjunctivitis and Asthma.

Allergen immunotherapy (AIT) is a recognized key therapeutic modality for the treatment of allergic respiratory disease. Definitive studies have provided evidence-based data to demonstrate its effectiveness in allergic rhinitis and asthma due to the inhalation of proteinaceous allergic substances from specific seasonal pollens, dust mites, animal allergens, and certain mold spores. Over the ensuing decades, laboratory investigations have provided objective evidence to demonstrate immunologic changes, including production of protective IgG antibody, suppression of IgE antibody, upregulation of regulatory T cells, and induction of a state of immune tolerance to the offending allergen(s). Tangential to this work were carefully designed clinical studies that defined allergen dose and duration of treatment, established the importance of preparing extracts with standardized allergens (or well-defined extracts) based on major protein moieties, and used allergen provocation models to demonstrate efficacy superior to placebo. In the United States, the use of subcutaneous immunotherapy extracts for AIT was grandfathered in by the Food and Drug Administration based on expert literature review. In contrast, sublingual tablet immunotherapy underwent formal clinical development programs (phase I-III clinical trials) that provided the necessary clinical evidence for safety and efficacy that led to regulatory agency approvals for the treatment of allergic rhinitis in properly characterized patients with allergy. The allergy specialist's treatment options currently include traditional subcutaneous AIT and specific sublingual tablets approved for grass, ragweed, house dust mites, trees belonging to the birch-homologous group, and Japanese cedar. Tangential to this are sublingual drops that are increasingly being used off-label (albeit not approved by the Food and Drug Administration) in the United States. This article will review the evidence-based literature supporting the use of these forms of AIT, as well as focus on several current controversies and gaps in our knowledge base that have relevance for the appropriate selection of patients for treatment with specific AIT.

Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE.

BACKGROUND: Previous trials have demonstrated the efficacy, safety, and optimal dosage of the 5-grass pollen sublingual tablet for adults and children with grass pollen-induced allergic rhinoconjunctivitis. OBJECTIVES: We sought to evaluate the efficacy and safety of 300 index of reactivity (IR) 5-grass pollen sublingual tablet in US adults. METHODS: Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater (scale, 0-18) during the previous grass pollen season were randomized in a double-blind, placebo-controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season. The primary efficacy end point was the daily Combined Score (CS; scale, 0-3), which integrates symptoms and rescue medication use. RESULTS: Four hundred seventy-three participants were randomized. The mean daily CS over the pollen period was significantly lower in the active treatment group versus the placebo group (least-squares mean difference: -0.13; 95% CI, -0.19 to -0.06; P = .0003; relative reduction: 28.2%; 95% CI, 13.0% to 43.4%). In placebo-treated participants, the daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass-specific serum IgE of less than 0.1 kU/L (n = 23) and 0.46 in those with baseline timothy grass-specific serum IgE of 0.1 kU/L or greater (n = 204). The most frequent reported adverse events were oral pruritus, throat irritation, and nasopharyngitis. There were no reports of anaphylaxis, and no actively treated participant received epinephrine. CONCLUSION: In US adults with grass pollen-induced allergic rhinoconjunctivitis, preseasonal and coseasonal treatment with 300IR 5-grass pollen sublingual tablet demonstrated clinically meaningful efficacy, especially in study subjects with measurable timothy grass-specific serum IgE. Use of 300IR 5-grass pollen sublingual tablet was safe and well tolerated. A requirement for a measurable level of allergen-specific serum IgE should be considered in future studies in this field.

Dose Adjustment After Gaps in Administration of Subcutaneous Immunotherapy From a Past Survey: Work Group Report of the AAAAI Allergen Standardization and Allergy Diagnostics Committee.

The allergen immunotherapy practice parameters third update recommendations on dose adjustment after a gap in administration during the build-up are based solely on expert opinion, and no recommendations for gaps during maintenance are given. In a previous survey among American Academy of Allergy, Asthma & Immunology (AAAAI) members on subcutaneous allergen immunotherapy, this was addressed, but details were never published. Members of the Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee of the AAAAI convened a workgroup to address this issue and reanalyze results on the particular survey section. Build-up: many practitioners start dose-adjusting if a patient comes in 14.1/14 days (mean/median) after the last dose and restart immunotherapy after an interruption of 85/90 days. Dosing frequency during maintenance is generally every 3 (12%) to 4 weeks (73%). Maintenance: allergists start dose-adjusting if a patient comes in 5.1/5 weeks (mean/median) after the last dose and completely restart after an interruption of 16/12 weeks (some replied in days [90.4/90 days] or months [4.43/4 months]). Subgroups: physicians with ≥11 years in practice in nonacademic centers or rural/suburban settings tolerate longer gaps before restarting subcutaneous immunotherapy (SCIT). There is no uniform dose-adjustment protocol after gaps in SCIT administration. Prospective studies shall have to help find the best trade-off between safety (dose reduction) without giving in on efficacy (too much dose reduction).

Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults.

BACKGROUND: Immunotherapy for allergic rhinoconjunctivitis (ARC) in North America is generally administered subcutaneously, but alternative formulations might be safer and more convenient. Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data. OBJECTIVE: We sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet (AIT) treatment in North American subjects with ARC. METHODS: Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were randomized to once-daily 2,800 bioequivalent allergen units of standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 standardized quality tablet, containing approximately 15 µg of Phl p 5) or placebo approximately 16 weeks before the 2009 grass pollen season (GPS). The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS. Rhinoconjunctivitis Quality of Life Questionnaire with standardized activities (RQLQ[S]) scores, Phl p 5-specific IgG4 levels, and IgE-blocking factor levels were additional end points. Adverse events (AEs) were monitored for safety. RESULTS: Relative to placebo, grass AIT treatment improved total combined scores by 20% (P = .005), daily symptom scores by 18% (P = .02), and RQLQ(S) scores by 17% (P = .02). Daily medication scores were improved by 26% and trended toward significance (P = .08). Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS (P < .001). Grass AIT treatment was safe and well tolerated. The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise. In the grass AIT group, 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction (local site reactions, chest discomfort, and rash). CONCLUSIONS: Timothy grass AIT treatment (cross-reactive with related Pooideae grasses) was demonstrated to be effective, generally safe, and well tolerated in North American adults with grass pollen-induced ARC.

New insights in mite immunotherapy - sublingual tablets.

PURPOSE OF REVIEW: Sublingual tablet immunotherapy has been demonstrated to be effective for allergies induced by exposure to grass, ragweed, specific trees (Japanese Cedar; birch homologous tree mix), and house dust mites (HDM). This review provides both an overview of the evidence-based clinical studies that address the use of the HDM SLIT-tablet for the treatment of HDM-induced allergic rhinitis/conjunctivitis and its appropriate use in carefully selected asthmatic patients and provides the clinician with practical management considerations. RECENT FINDINGS: Solid evidence-based clinical studies have shown that the HDM SLIT-tablet is both well tolerated in patients with mild-to-moderate asthma and has demonstrated a meaningful improvement in exacerbations, need for rescue medication, quality of life, and asthma control. SUMMARY: The HDM SLIT-tablet provides the allergy specialist with a well-tolerated treatment that has established superior safety to subcutaneous injection therapy, which can be administered easily as a sublingual dissolvable tablet, and which provides the opportunity to address one of the more difficult aspects in the management of an inducer of perennial allergic disease - that of persistent airway inflammation and allergic asthma.

One Hundred Ten Years of Allergen Immunotherapy: A Broad Look Into the Future.

Allergen immunotherapy (AIT) is the only disease-modifying treatment option for patients with type 1-mediated allergic diseases such as allergic rhinitis/rhinoconjunctivitis with/without allergic asthma. Although many innovations have been developed since the first clinical report of Noon et al in 1911, the improvement of clinical efficacy and tolerability of this treatment is still an important unmet need. Hence, much progress has been made in the characterization of the cell types, cytokines, and intracellular signaling events involved in the development, maintenance, and regulation of allergic reactions, and also in the understanding of the mechanisms of tolerance induction in AIT. This comprehensive review aims to summarize the current innovative approaches in AIT, but also gives an outlook on promising candidates of the future. On the basis of an extensive literature review, integrating a clinical point of view, this article focuses on recent and future innovations regarding biologicals, allergen-derived peptides, recombinant allergens, "Toll"-like receptor agonists and other adjuvants, and novel application routes being developed for future AIT.

Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.

BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons. RESULTS: There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody. A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19). CONCLUSIONS: In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).

Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.