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

BACKGROUND: Allergic 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. OBJECTIVE: To evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. METHODS: Subgroup (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). RESULTS: Significant (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. CONCLUSION: Treatment 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.

A practical guide to the sublingual immunotherapy tablet adverse event profile: implications for clinical practice.

OBJECTIVES: Treatment with allergy immunotherapy improves allergic rhinoconjunctivitis, but can also improve comorbidities associated with allergic rhinitis such as asthma. Sublingual immunotherapy (SLIT)-tablets are a convenient and efficacious method of allergy immunotherapy. They are self-administered after the first tablet has been provided under medical supervision. Therapy may elicit local reactions or, rarely, systemic allergic reactions. The objective of this report is to inform healthcare practitioners about the safety and tolerability profile of SLIT-tablets and use this information to provide practical guidance that may inform patients regarding potential adverse reactions and how to manage them. METHODS: Pooled analyses of safety data from completed randomized, multicenter, double-blind, placebo-controlled phase 2 and phase 3 US and EU trials of timothy grass, short ragweed, and SQ house dust mite SLIT-tablets were conducted to characterize safety and tolerability. RESULTS: SLIT-tablets are generally well tolerated. No life-threatening events, serious systemic allergic reactions, or events that compromised the airway have been reported. The most common treatment-related adverse events (AEs) are oral site reactions, most of which begin on day 1 of treatment, recur for less than 2 weeks, and resolve after approximately 30-60 minutes. Systemic allergic reactions have been managed with conventional pharmacotherapy. Reactions treated with epinephrine are uncommon, but have been reported. Treatment of AEs, treatment discontinuation considerations, and patient FAQs regarding SLIT-tablet safety/tolerability are discussed. CONCLUSIONS: This report gives healthcare providers valuable information to educate patients regarding what to expect in terms of SLIT-tablet safety and tolerability. Practical guidance is also provided to ensure proper treatment of any adverse reactions.

Immunogenicity and safety of omalizumab in pre-filled syringes in patients with allergic (IgE-mediated) asthma.

BACKGROUND: Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled moderate-to-severe or severe persistent allergic asthma, was developed as a lyophilised powder for reconstitution. A liquid formulation in pre-filled syringes has now been developed. The purpose of this study was to assess the immunogenicity and safety of this liquid formulation. METHODS: In this multinational, open-label, single-arm study, patients (≥12 years) with moderate-to-severe allergic asthma were treated for 24 weeks with the liquid formulation of omalizumab (75 or 150 mg in a pre-filled syringe) at 2 or 4 week intervals. Immunogenicity was assessed by measurement of human anti-therapeutic antibody (ATA) levels. Safety was assessed by monitoring adverse events (AEs), haematology, blood chemistry, urine analysis and vital signs. RESULTS: A total of 155 patients were enrolled in the study. No patient had a confirmed positive ATA test result. Most frequent individual AEs were asthma (17.4%), sinusitis (17.4%) and upper respiratory tract infection (11.6%). Fourteen patients (9.0%) had serious AEs and there was one death (not treatment related). There were no cases of anaphylaxis according to Sampson criteria. Most patients remained within normal ranges for haematology and biochemistry laboratory variables. CONCLUSIONS: Omalizumab in pre-filled syringes was not associated with immunogenicity. This novel formulation, which does not require reconstitution, had a safety profile consistent with the lyophilised formulation. A limitation of this study is that efficacy of omalizumab in the treatment of asthma was not specifically addressed herein. Clinicaltrials.gov identifier: NCT00500539.

A 26-week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the effect of omalizumab on asthma control in patients with persistent allergic asthma.

OBJECTIVE: The 2007 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines shifted the focus of care from asthma severity to ongoing assessment of asthma control using the components of impairment and risk. We evaluated the effect of omalizumab on asthma control in patients with persistent allergic asthma inadequately controlled with NHLBI Step 4 or above asthma therapy. METHODS: In this double-blind, placebo-controlled study, patients ≥12 years (n = 271) received omalizumab (n = 136) or placebo (n = 135) every 2 or 4 weeks for 24 weeks. The primary efficacy variable, change from baseline in Asthma Control Test (ACT) total score, and Investigator's Global Evaluation of Treatment Effectiveness (IGETE, secondary efficacy variable) were evaluated at week 24. RESULTS: ACT score improved more with omalizumab compared with placebo (least squares means [LSMs]: 5.01, 4.36); however, the difference was not significant (p = .1779). Similarly, IGETE was not significantly different (p = .1177), but more patients treated with omalizumab (26/127, 20%) compared with placebo (19/131, 15%) had IGETE rated as "Excellent." Significant benefits were observed for omalizumab compared with placebo for change in ACT score (LSMs: 6.66, 5.27; p = .0334) and IGETE (p = .0321) at week 24 in a subgroup of patients with very poorly controlled asthma (ACT ≤ 15) at baseline. There were no significant differences for the subgroup of patients with forced expiratory volume in 1 second ≤ 80% predicted at baseline. Adverse events (AEs) were similar between groups with no drug-related serious AEs or deaths. CONCLUSIONS: For allergic asthma patients with NHLBI Step 4 or above asthma therapy, omalizumab consistently improved asthma control; however, compared with placebo, differences were not significant. Placebo-treated patients had substantial improvement in their ACT score, which may have limited the ability to detect differences between treatment groups. Subgroup analyses showed significant improvements with omalizumab versus placebo in patients with very poorly controlled asthma.

A preference evaluation study comparing the sensory attributes of mometasone furoate and fluticasone propionate nasal sprays by patients with allergic rhinitis.

OBJECTIVE: Data on intranasal corticosteroids suggest that individual product attributes may influence patient preference for therapy in allergic rhinitis. The study objective was to compare product sensory attributes and their impact upon patient preference for scent-free mometasone furoate nasal spray (MFNS) versus fluticasone propionate nasal spray (FPNS) in patients with symptomatic allergic rhinitis. METHODS: In a double-blind, crossover study, 100 patients were randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients rated the study drugs by completing an individual product sensory attributes questionnaire at the end of each period of drug administration. An overall sensory preference questionnaire was completed following crossover. RESULTS: A significantly greater number of patients preferred MFNS to FPNS (p < 0.05). MFNS was superior for a number of individual sensory attributes based on mean patient ratings: significantly fewer patients perceived scent/odor (immediately and 2 minutes after drug administration; p < 0.001), taste (immediately after drug administration; p = 0.002), and after-taste (2 minutes after drug administration; p = 0.007) with MFNS compared with FPNS. Similarly, product sensory attribute preference data demonstrated that twice the number of patients preferred MFNS to FPNS for scent/odor (p = 0.0005), immediate taste (p = 0.005), and after-taste (p = 0.005). Fifty-four percent of patients said they would choose a prescription for MFNS compared with 33% for FPNS (p = 0.03). In addition, 47% of patients would be more likely to comply (use daily as directed) with MFNS compared with 25% with FPNS (p = 0.03). CONCLUSION: Several individual sensory attributes of MFNS were rated significantly superior to FPNS. Overall, based on the tested sensory attributes, patients preferred MFNS to FPNS therapy for the treatment of allergic rhinitis.

Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is an effective therapy for symptoms of seasonal allergic rhinitis, a disease governed by patients' individual sensitivity and exposure to relevant allergens. OBJECTIVE: To evaluate the relationship of montelukast treatment effect vs pollen exposure in studies conducted during 3 consecutive fall allergy seasons. METHOD: A combined analysis of these multicenter, randomized, double-blind, parallel-group studies was performed; 1 of the 3 studies is presented for the first time in this article. After a placebo run-in period, 1,862 symptomatic patients were randomly assigned to receive either a 10-mg montelukast tablet (n = 929) or placebo (n = 933) once daily for 2 weeks. Pollen exposure was summarized by mean daily weed pollen count. The interaction between treatment effect and pollen exposure was evaluated on the primary efficacy endpoint and daytime nasal symptom score, as rated by patients; also evaluated was the influence of the timing of the 2-week treatment period relative to the peak of the weed pollen season. RESULTS: Montelukast significantly improved daytime nasal symptoms score and individual scores of congestion, rhinorrhea, itching, and sneezing compared with placebo. There was a significant interaction (P < .043) between treatment effect and weed pollen exposure; a larger treatment effect was noted in patients exposed to higher pollen counts. An interaction between treatment effect and timing of treatment in relation to peak pollen season was suggested. CONCLUSIONS: Montelukast significantly improved daytime nasal symptoms score in patients with seasonal allergic rhinitis, and the effect was greater in patients exposed to higher pollen levels.