Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps.

BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Hydroxychloroquine improves airflow and lowers circulating IgE levels in subjects with moderate symptomatic asthma.

BACKGROUND: Although antiinflammatory therapy is accepted as the cornerstone of asthma treatment, available systemic immunosuppressive agents are not widely used because of justified concerns over potential toxicity. Hydroxychloroquine (HCQ) is a well-tolerated, safe immunomodulating drug, with proven efficacy in rheumatic diseases and known actions that suggest potential utility in the treatment of asthma. OBJECTIVE: We sought to assess the effectiveness of HCQ in subjects with moderate symptomatic asthma. METHODS: Symptomatic asthmatic subjects receiving stable doses of at least 6 puffs of inhaled corticosteroid per day with daily need for beta2-adrenergic agonists were studied. After baseline run-in, these subjects were randomized to 30 weeks of HCQ (n = 8) or placebo (n = 9). Objective measures included change from baseline mean FEV1, morning and evening peak flows, beta2-agonist use, IgE level, and need for rescue corticosteroids. Subjective symptom scores from bidaily diaries were also obtained. RESULTS: In the treatment group, mean FEV1 at the last 2 visits on therapy increased by 10.8% (P < .05), morning peak flows rose 16.2% (P < .03), evening peak flows rose 14.2% (P < .04), and beta2-agonist use fell 18.6% (P < .03). Mean IgE level declined 48% from 240 to 125 IU/mL. (P < .05). In the placebo group no significant change in these parameters occurred. Comparison of changes in these objective measures between the treatment and placebo groups failed to reach significance in the small population studied. Corticosteroid rescue interventions were required in 4 patients receiving placebo and 2 receiving HCQ. HCQ was well tolerated without notable side effects. CONCLUSIONS: Although the size of our sample population precludes definitive conclusions, these findings extend previous open-label observations. The late improvement in the HCQ group is consistent with its known slow onset of action. Further studies are warranted to confirm the antiasthmatic and antiallergic effects of HCQ and to investigate its potential as a disease-modifying agent.