Iñaki Izquierdo

Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study.

Background:  Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first‐line treatment. Rupatadine is a new potent nonsedative anti‐H1.

Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber

BACKGROUND Rupatadine is a novel compound with potent dual antihistamine and platelet-activating factor antagonist activities and no sedative effects. OBJECTIVE To evaluate the efficacy of rupatadine, 10 mg once daily, and placebo on allergen-induced symptoms (including nasal congestion), nasal airflow, nasal secretion, and subjective tolerability in response to grass pollen in a controlled allergen-exposure chamber. METHODS In a randomized, double-blind, placebo-controlled, crossover trial, 45 patients with a history of seasonal allergic rhinitis received rupatadine or placebo every morning for 8 days in 2 different periods separated by a 14-day washout interval. On day 8 of each crossover period, patients underwent a 6-hour allergen exposure in the Vienna Challenge Chamber, where a constant and homogeneous concentration of aeroallergens was maintained. Subjective and objective assessments were performed online during the exposure. RESULTS Subjective single and composite nasal and nonnasal symptoms were consistently less severe with rupatadine use than with placebo use starting from the first evaluation at 15 minutes to the end of the 6-hour Vienna Challenge Chamber challenge, with the most significant effects seen for nasal rhinorrhea, nasal itching, sneezing attacks, and total nasal symptoms (P < .001 for all). All the other symptoms (including nasal congestion, P < or = .005) were also significantly reduced with active treatment compared with placebo use. Mean secretion weights and overall feeling of complaint were significantly lower with rupatadine therapy than with placebo use (P < or = .001). Overall, rupatadine treatment was well tolerated. CONCLUSION Rupatadine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to aeroallergens in a controlled exposure chamber.

Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria

BACKGROUND Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor. OBJECTIVE To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU. METHODS A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. RESULTS After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment. CONCLUSION Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.

A 12‐week placebo‐controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis

Background:  With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1‐antihistamines have demonstrated anti‐allergic properties, which could possibly enhance their effectiveness in long‐term periods of treatment.

Validation of the COPD severity score for use in primary care: the NEREA study

Spirometry is underused for the assessment of severity of chronic obstructive pulmonary disease (COPD) in primary care (PC). Therefore, simple assessment tools are required in this setting. The aim of the present study was to validate the COPD severity score (COPDSS) for use in PC. A multicentric study was carried out in stable COPD patients in PC. The concurrent validity of the COPDSS was evaluated by examining the association between COPDSS, COPD clinical indicators and the London Chest Activity of Daily Living (LCADL) scale, European quality of life (EuroQOL) questionnaires and Charlson comorbidity index. A total of 837 patients with COPD were analysed (males 84.3%; mean±sd age 68±11 yrs; forced expiratory volume in one second 54.6±17.7% of the predicted value). A strong correlation was found between COPDSS and dyspnoea level and a moderate correlation between COPDSS and exacerbation number. The COPDSS discriminated between patients with varying degrees of dyspnoea (area under receiver operating characteristic (ROC) curve 0.837), and according to number of exacerbations in the last year (area under ROC curve 0.773). Higher COPDSS scores were significantly associated with lower EuroQOL scores, lower EuroQOL visual analogue scale scores and higher LCADL scores. The present results indicate that the chronic obstructive pulmonary disease severity score is a useful and reliable tool for assessing the severity of chronic obstructive pulmonary disease in primary care.

Health-related quality of life in allergic rhinitis: comparing the short form ESPRINT-15 and MiniRQLQ questionnaires

Background: We compared the psychometric properties of the ESPRINT‐15, the short form of a new Spanish instrument to measure health‐related quality of life in allergic rhinitis (AR) patients, with those of the Mini‐Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ).

COPD severity score as a predictor of failure in exacerbations of COPD. The ESFERA study

BACKGROUND Exacerbations are a frequent cause of morbidity and mortality in COPD. It is crucial to identify risk factors for failure after treatment of exacerbations of COPD. This study evaluates the COPD severity score (COPDSS) as a predictor of clinical failure, together with other severity, activity and quality of life measurements, in patients with exacerbated COPD. METHOD Multicenter, prospective, observational study in ambulatory patients with exacerbation of COPD. The patients completed the COPDSS, the London Chest Activities of Daily Living (LCADL) and the EuroQol 5D (EQ-5D). A follow-up visit was scheduled one month after presentation with the exacerbation to assess the clinical evolution. RESULTS A total of 346 patients were included (mean age 68.5 years (SD=9.5 years and 90.7% male) and mean FEV(1)(% predicted) 46.9% (SD=17)). After one month, 28.2% of episodes were classified as failures, with half of them requiring hospital admission. Patients who failed were more frequently active smokers, with more severe dyspnoea at presentation and worse lung function. They had significantly worse scores of COPDSS, LCADL, EQ-5D index and EQ-5D visual analogue score (VAS) and shorter mean time walking per day. ROC analysis of relationship between COPDSS and failure gave AUC 0.72, which improved only to 0.77 when the other significant variables in univariate analysis were considered. CONCLUSIONS Clinical failure after ambulatory treatment of exacerbation of COPD is frequent. Usual markers of severity (impaired lung function, active smoking and severe dyspnoea) are associated with failure; however, a short severity questionnaire (COPDSS) provides better predictive value than the usual variables.

Influence of food on the oral bioavailability of rupatadine tablets in healthy volunteers: A single-dose, randomized, open-label, two-way crossover study

BACKGROUND Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries. OBJECTIVE The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine. METHODS This was a single-dose, randomized, open-label, 2-way crossover study in which healthy male and female volunteers received a single, 20-mg oral dose of rupatadine under fed and fasting conditions. Blood samples were collected and plasma concentrations of rupatadine and its active metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examinations, electrocardiograms, and laboratory tolerability tests immediately before each treatment period and at the final visit of the study. RESULTS Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal distribution of sex. A significant increase in AUC from drug administration to the final quantifiable sample (AUC(0-t)) and AUC from drug administration to infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions without affecting C(max). The ratios (90% CI) of the mean log-transformed AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). Plasma concentration-time profiles of desloratadine and 3-hydroxydesloratadine were similar with and without food, and no differences were seen for AUC(0-t), AUC(0-infinity), or C(max). Seven (28%) subjects reported > or =1 AE. All AEs were mild, resolved spontaneously, and did not affect the outcome of the study. CONCLUSIONS The results of this study indicate that concomitant intake of food with a single 20-mg oral dose of rupatadine exhibits a significant increase in rupatadine bioavailability. Despite the absence of bioequivalence, the drug was well tolerated under fed and fasting conditions, and no major changes in severity and/or prevalence of AEs were reported.

Safety of Rupatadine Administered Over a Period of 1 Year in the Treatment of Persistent Allergic Rhinitis

AbstractBackground: Rupatadine (Rupafin®), a novel antihistamine approved recently in Europe for the treatment of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged ≥12 years, has been shown to be highly efficacious, and as safe and well tolerated as other commonly employed antihistamines in the treatment of allergic disease. There are, however, few data on the long-term safety of these antihistamines derived in accordance with the clinical safety recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA) and the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline. Objective: To assess the safety and tolerability of treatment with rupatadine 10 mg/day for 12 months in subjects with persistent AR (PER). Methods: A multicentre, open-label, phase IV study in patients recruited from 33 centres in Spain, from September 2002 to November 2005. The study enrolled 324 male and female patients (aged 12–70 years) with a medical history of PER for at least 12 months and a documented positive skin-prick test to an appropriate allergen. On 4 of the 7 days prior to start of treatment, the patients were required to have a minimum total nasal symptom score (TNSS [for sneezing, rhinorrhoea, nasal obstruction/congestion and nasal itching]) of ≥5. Of the 324 eligible patients starting treatment, 120 needed to be treated for more than 6 months and were followed up until the end of 12 months. All patients received rupatadine 10 mg/day and were allowed to continue their normal concomitant medication for all conditions, other than rhinitis, for up to 6 or 12 months. Safety was assessed by means of adverse events (AEs) reported by patients or detected by investigators, scheduled centralized ECG with special attention to Bazzet corrected QT interval (QTcB) and standard laboratory investigations. Results: Assessment of treatment compliance rates indicated 90% and 83% of patients to be compliant during the 1–6 months and 1–12 months treatment periods, respectively, with compliance rates >80% being associated with the majority of the study population reporting at least one AE. Overall, 74.1% and 65.8% of the patients reported at least one AE during the 1–6 months and 1–12 months treatment periods, respectively, compared with 20.4% and 10.8% of patients reporting at least one treatment-related AE during these periods. Disorders of the nervous system and respiratory thoracic and media-stinal system, in particular headache, somnolence and catarrh, were the three most common AEs reported by >5% of the patients during both treatment periods. Detailed ECG assessments demonstrated no clinically relevant abnormal ECG findings, nor any QTcB increases >60 msec or QTcB values >470 msec for any patient at any time during treatment. Serious AEs were reported in seven patients, of whom six were considered as unlikely to be related to rupatadine treatment, whereas one involving increased blood enzyme levels was considered as possibly related to rupatadine treatment. Conclusion: This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER.

The impact of allergic rhinitis on symptoms, and quality of life using the new criterion of ARIA severity classification.

INTRODUCTION Allergic rhinitis (AR) is a common disease with major socieconomic burden and a significant impact on quality of life. OBJECTIVE The objective of the study was to assess the impact of AR severity, using the modified ARIA (m-ARIA) severity criterion in order to discriminate among moderate and severe AR, in symptoms and quality of life assessed with the questionnaire ESPRINT-15. METHODS The specific quality of life questionnaire (ESPRINT-15) was applied in over thousand untreated RA patients. Severity was evaluated by the m-ARIA classification, which categorizes AR as mild, moderate, and severe. Nasal symptoms were evaluated by using categorized (none, low, middle, and high) Total Four Symptom Score (T4SS). RESULTS Using the m-ARIA severity classification, significant differences in quality of life, both global score and specific domains, and categorized T4SS were found among the AR severity groups. CONCLUSION Modified ARIA severity classification in mild, moderate, and severe allergic rhinitis clearly discriminates the impact of AR in all domains of quality of life and categorized symptom`s score.