Ciclesonide inhibits Zika virus replication in vitro / 药学学报

Zika virus (ZIKV) is an emerging mosquito-borne virus that is associated with severe congenital brain malformations in the fetus and Guillain-Barré syndrome in adults. However, there are currently no drugs or preventive vaccines approved for ZIKV infection. Here, ciclesonide has been found significantly against ZIKV activity by plaque and cytotoxicity assays in vitro, and its 50% effective concentration (EC50) to ZIKV SZ01 and MR766 are (0.40 ± 0.22) and (1.59 ± 1.08) μmol·L-1, respectively. Its 50% cytotoxic concentration (CC50) to Vero cells are (64.70 ± 7.33) μmol·L-1; Virus yield reduction and Western blot assays showed that ciclesonide can inhibit replication of ZIKV. In addition, ciclesonide can also inhibit the replication of ZIKV in A549 cells; the results of time of drug addition analysis indicated that ciclesonide mainly acts on the ZIKV RNA synthesis stage. Ciclesonide can also inhibit the internalization of ZIKV. These results indicated that ciclesonide is a potential drug against ZIKV.

Efficacy of ciclesonide, budesonide and beclomethasone dipropionate in moderate persistent bronchial asthma: a comparative study

Background: The objective of the present study was to compare the efficacy and adverse effects of ciclesonide with that of budesonide and beclomethasone dipropionate in moderate persistent cases of bronchial asthma.Methods: This was an open label, randomized parallel group study done in Government General and Chest Hospital, Hyderabad for a period of 12 weeks. Each group had 20 patients. Group A was given ciclesonide inhalational therapy 160 mcg once daily. Group B was given budesonide inhalational therapy 400 mcg twice daily. Group C was given beclomethasone dipropionate inhalational therapy 400 mcg twice daily.Results: Symptomatic improvement was observed in all three groups. At end point, mean FEV1 in ciclesonide treatment group improved by 23.84% compared with 15.24% in budesonide and 12.93% in beclomethasone treatment groups. At end point, mean FVC value in ciclesonide treatment group improved by 6.44% compared with 1.5% in budesonide and 1.06% in beclomethasone groups. Mean FEV1/FVC also improved by 16.56% in ciclesonide group compared with 13.68% in budesonide and 11.93% in beclomethasone groups. No adverse effects were reported in any of the treatment groups.Conclusions: This study showed that ciclesonide is superior to budesonide and beclomethasone in improving lung function, decreasing symptoms and need for rescue medication in moderate persistent asthma.

Prescription Profile and Clinical Outcomes in Patients with Allergic Rhinitis Treated with Oral Antihistamines or Nasal Corticosteroids

Abstract Introduction Oral antihistamines and intranasal corticosteroids have been shown to be effective and safe for the treatment of allergic rhinitis; however, the evidence suggests a level of superiority of corticosteroids, so they should be preferred over the former. Objective To know the prescription profile of two second generation antihistamines (cetirizine and levocetirizine) and two nasal corticosteroids (mometasone and furoateciclesonide) in a cohort of patients with allergic rhinitis, and to compare the clinical outcomes obtained. Methods A cohort study was carried including patients with allergic rhinitis treated with cetirizine, levocetirizine, mometasone furoate or ciclesonide. The improvement was evaluated with the total nasal symptoms score (TNSS). This scale yields results between 0 and 12. Zero indicates absence of symptoms. Results A total of 314 patients completed 12 weeks of follow-up. Seventy-five percent were treated with antihistamines, 20% with corticosteroids, and 5% with a combination of the above. The TNSS median for corticosteroid was 2.5 points; for antihistamines, its was 5 points, and for combination, it was 4 points. We found differences between corticosteroids and antihistamines. Conclusion The prescription percentage of second generation oral antihistamines is higher than that of intranasal corticosteroids. However, patients with allergic rhinitis treated with the second option obtained better control of symptoms.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis / Eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene: uma revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = −0.56; 95% CI −0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I2 = 24%), Instantaneous Total Nasal Symptom Score (MD = −0.57; 95% CI −0.75 to −0.39, p < 0.00001) with heterogeneity (p = 0.34, I2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = −0.15; 95% CI −0.18 to −0.13, p < 0.00001) with heterogeneity (p = 0.12, I2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = −0.27; 95% CI −0.39 to −0.15, p < 0.00001) with heterogeneity (p = 0.58, I 2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica que afeta um a cada seis indivíduos. A rinite alérgica perene é responsável por 40% dos casos de rinite alérgica. A ciclesonida é um dos corticosteroides intranasais mais novos para o tratamento dessa condição clínica. Objetivo: Avaliar a eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene. Método: Uma busca foi feita nos bancos de dados Pubmed, Scientific Citation Index, Embase e Clinical Trial Registries por ensaios clínicos randomizados e Cochrane Central Register of Controlled Trials por estudos controlados randomizados que comparassem ciclesonida com placebo no tratamento da rinite alérgica perene. Resultados: Oito estudos foram incluídos. Em comparação com os grupos placebo, os grupos ciclesonida mostraram diminuição significante no escore do Reflective Total Nasal Symptom Score (DM = −0,56; IC 95%: −0,72 a −0,39, p < 0,00001) com heterogeneidade (p = 0,19, I2 = 24%), do Instantaneous Total Nasal Symptom Score (DM = −0,57; IC95%: −0,75 a −0,39, p < 0,00001) com heterogeneidade (p = 0,34, I2 = 11%). Um efeito significante no escore do Reflective Nasal Symptom Score Subtotal (DM = −0,15; IC 95%: −0,18 a −0,13, p < 0,00001) com heterogeneidade (p = 0,12, I2 = 24%) também foi demonstrado. O escore do Rhinoconjunctivitis Quality of Life Questionnaire score (RQLQs) (DM = −0,27; IC 95%: −0,39 a −0,15, p < 0,00001) com heterogeneidade (p = 0,58, I2 = 0%) também foi significantemente reduzido no tratamento com ciclesonida. Além disso, a diferença em relação aos eventos adversos emergentes do tratamento entre os dois grupos não foi significante. Conclusão: A ciclesonida pode melhorar a rinite alérgica perene sem aumentar os eventos adversos. Esse fármaco pode ser outra opção valiosa para a rinite alérgica perene no futuro.

Effect of Proparacaine in a Mouse Model of Allergic Rhinitis

OBJECTIVES: Lidocaine, a local anaesthetic is a treatment option in uncontrolled asthma due to its immunomodulatory effects. In the present study, proparacaine (PPC), a derivative of lidocaine was examined for its therapeutic application in a mouse model of allergic rhinitis. METHODS: The mice were grouped into 4 groups: control group, allergic rhinitis (AR) group, ciclesonide (CIC) group, and PPC group. Nasal symptom scores, eosinophil counts, goblet cell counts, and mast cells counts in the nasal mucosa were measured. Serum ovalbumin (OVA)-specific immunoglobulin (Ig) E, OVA-specific IgG1, OVA-specific IgG2a, interleukin (IL)-4, IL-5, and cortisol levels were measured. RESULTS: Intranasal administration of PPC significantly decreased nasal symptoms, number of eosinophils, goblet cells, and mast cells in the lamina propria of the nasal mucosa. Serum OVA-specific IgE, OVA-specific IgG1, OVA-specific IgG2a was significantly higher in the AR compared with the control group. Serum level of IL-4 was significantly lower in the CIC group and PPC group in comparison with AR group. Serum IL-5 showed no significant difference among all groups. No significant difference in serum cortisol levels was observed among the 4 groups. CONCLUSION: PPC appears to have a therapeutic potential in treatment of allergic rhinitis in a mouse model by reducing eosinophil, goblet cell, and mast cell infiltration in the nasal mucosa.

Comparison of Intranasal Ciclesonide, Oral Levocetirizine, and Combination Treatment for Allergic Rhinitis

PURPOSE: To evaluate the efficacy and safety of once-daily ciclesonide in comparison to both levocetirizine alone, and a ciclesonide/levocetirizine combination in patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Subjects exhibiting moderate to severe allergic rhinitis for longer than 1 year were randomized in an open-label, 3-arm, parallel group, multicenter study. Subjects received 200 microg ciclesonide, 5 mg levocetirizine, or a combination of both. Changes from baseline until the end-of-study visit (2 weeks following) were evaluated by reflective total nasal symptom scores (rTNSSs), reflective total ocular symptom scores (rTOSSs), physician-assessed overall nasal signs and symptoms severity (PANS), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). RESULTS: Significant improvements in rTNSS, PANS, and RQLQ in the ciclesonide monotherapy group were observed in comparison to the levocetirizine alone group. Three individual symptoms of rTNSS, including runny nose, nasal itching, and congestion, were improved in the ciclesonide-treated group. rTOSS scores for ciclesonide monotherapy improved from baseline, but no superiority over levocetirizine was shown. The absolute score and changes in rTNSS and PANS were positively correlated. Ciclesonide spray was more effective than levocetirizine in reducing nasal symptoms in both SAR and PAR patients. Ciclesonide and levocetrizine were well tolerated alone and in combination. CONCLUSIONS: Our results provide support for an AR and its Impact on Asthma (ARIA) recommendation stipulating that ciclesonide is superior to levocetirizine for the treatment of AR, with tolerable safety. Addition of levocetirizine to ciclesonide did not give further clinical benefit over monotherapy.

Comparative efficacy of inhaled ciclesonide, budesonide, and fluticasone in mild to moderately persistent bronchial asthma.

Background: Bronchodilators and glucocorticoids have been proven to be very effective and safe in asthma treatment, which recommend the use of steroids and β2-agonist (long or short acting) as the first line of treatment in of asthma. This study was aimed to compare the efficacy of three different inhaled corticosteroids ciclesonide, budesonide, and fluticasone in bronchial asthma. Methods: A total of 30 patients with mild to moderately persistent bronchial asthma was selected as per the NAEPP classification in the expert panel report (EPR) update 2002, NHLBL USA 2003. They were randomly divided into 3 groups of 10 patients each, and they were given 3 different steroid inhalers (ciclesonide or budesonide or fluticasone). Baseline and post-therapy spirometry were performed on day 1 and after 2 months and 6 months of treatment. Data were analyzed using SPSS software. Results: It was observed that most of the cases (43.3%) were between 26 and 35 years of age with female preponderance (56.6%). Significant symptomatic improvement was observed in all 3 groups. The percentage of improvement in mean peak expiratory flow rate was 17%, 18%, and 18% in ciclesonide, budesonide, and fluticasone group, respectively. The percentage improvement of forced expiratory volume in 1 second (FEV1)/forced vital capacity after bronchodilatation was 18%, 18%, and 19% in ciclesonide, budesonide, and fluticasone group, respectively. The improvement in mean FEV1% predicted was 20%, 19%, and 21% in three groups, respectively. Conclusion: Steroid therapy along with β2-agonists showed a significant improvement in symptoms. There was no difference among the three different types of steroids.