Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid

Background: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. Methods: In this double-blind, placebo-controlled study (EudraCT: 2011-00067458), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG(4) and the incidence of adverse events (AEs). Results: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standarddose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical relevance: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured

Exploratory study of tolerability and immunological effect of a short up-dosing immunotherapy phase with a standardised allergen extract derived from pollen of Olea europaea

BACKGROUND: A new subcutaneous specific immunotherapy (SCIT) product adsorbed on aluminium hydroxide has been developed with a short and simplified up-dosing phase, containing a biologically standardized allergen pollen extract from Olea europaea. OBJECTIVE: To assess the tolerability profile of the updosing phase and its immunological effect, in terms of specific IgG(4) and IgE levels and immediate skin reactivity. MATERIAL AND METHODS: The study was an exploratory, multi-centre, open-label, single-arm, phase II/III clinical trial. Adults with a clinical history of allergic rhinoconjunctivitis with/without asthma due to sensitization to olive pollen were selected. Five up-dosing doses (300, 600, 3000, 6000 and 15000SQ+) were administered at weekly intervals, followed by a maintenance dose (15000SQ+) after 2 weeks. Adverse events were collected during the 30 min observation period after injections, after a telephone contact 2 days after each visit, and after reviewing the subjects’ diary. IgG(4) and IgE levels and immediate skin reactivity were evaluated at the beginning and at the end of the trial. RESULTS: Ninety-three subjects were included in the trial (mean age, 35.7 ± 10.3 years; women, 66.7 %). A total of 95 adverse drug reactions, all mild in intensity and non-serious, were reported during the trial: 85 local in 34.4 % subjects, 9 systemic in 4.3 % subjects and one non-specific (grade 0). Within 6 weeks, significant changes in IgG(4) and IgE levels and in immediate skin reactivity to Olea europaea were accomplished. CONCLUSION: This new SCIT derived from pollen of Olea europaea presented a good tolerability profile and induced significant immunological responses already after a 6 week treatment. However, the non-controlled design may limit the interpretation of these results. TRIAL REGISTRATION: EudraCT no: 2011-004852-20; ClinicalTrials.gov Identifier: NCT01674595

The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 year