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An environmental study of ophthalmic epinastine in patients with allergic conjunctivitis
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
tests (SPT) at the first appointment: 90 (53,9%) patients had PU as the only diagnosis and 77 (46,1%) had also asthma, rhinitis or eczema, with the following atopic distribution: positive SPT in PU - 27.7%; positive SPT in PU with associated allergic diseases - 57.1%. These differences were statistically significant (p=0,0001). There were very few reports of symptoms related with food, In conclusion, papular urticaria justified reference to our department of a significant number of patients. Patients with only PU had sensitization prevalence similar to the expected in Portuguese population (about 25%). In the group with associated allergic diseases, the prevalence was similar to the one found in the population with respiratory allergic disease, in the same age group. It's important to point out the absence of association between these clinical entities, allowing the avoidance of useless diagnostic measures and anxiety about allergic risk.
Abstracts
$237
itching. Epinastine 0.05% ophthalmic solution was effective, safe, and well tolerated in patients with seasonal allergic conjunctivitis.
Funding: Allergan lnc
676 Administration Pharmacokinetic and Safety Profile of EpinastineAfter Ocular in Patients with Allergic Conjunctivitis
V. Djuric, M. Bogic; Institute of Allergology and Immunology, Belgrade, YUGOSLAVIA. RATIONALE: Chronic urticaria is a frustrating diagnostic and therapeutic problem, very often without known cause. According to some authors it may be due to Helicobacter pylori infection. METHODS: Ten patients with chronic urticaria and gastric complaints were included in the study. Skin tests with common allergens were negative and laboratory tests did not help to find the cause of urticaria. Gastroduodenoscopy, biopsy of gastric mucosa and urease test were performed. Patients with Helicobacter pylori positive gastritis were treated with omeprazole, amoxicillin and metronidazole for 12 days and followed for 2 months. RESULTS: Helicobacter pylori positive gastritis was found in 8 patients. After the therapy, significant reduction in number of urticarial lesions and reduction in antihistamine therapy was achieved in 5 patients. CONCLUSIONS: Helicobacter pylori positive gastritis may play a role in the development of chronic urticaria in some of the patients.
D. Yu l, P. Ghosh 2, D. Tang-Liu3; lpharmacokinetics Department, Allergan Inc, Irvine, CA. 2Advisor of Medical Ophthalmology, Allergan Ltd, Wycombe, UNITED KINGDOM, 3pharmacokinetics Department, Allergan Inc, Invine, CA. RATIONALE: Epinastine hydrochloride (HCI), a new generation H1 and H2 receptor antagonist with the ability to stabilize mast cells, is being developed as a treatment for allergic conjunctivitis. We determined tear and plasma pharmacokinetics and the safety profile of ophthalmic epinastine. M E T H O D S : In this single-center, open label study, study personnel instilled 1 drop of epinastine HCI 0.05% in both eyes of 14 allergy patients once on day 0, BID through day 6, and TID on day 7. Serial plasma samples were collected on days 0, 1, and 4-7. Tears were collected on day 7. Epinastine concentrations were determined by a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: Epinastine quickly reached high concentration in tears, with Cmax = 27.1 _+46.2/.tg/mL (mean _+ SD) at 2 min post-dose. Plasma concentrations were approximately one million-fold lower, near the lower limit of quantitation (0.0I ng/mL). Cmax values were 0.025 _+0.008 ng/mL after a single dose and 0.042 _+0.014 ng/mL after 5.5 days of BID dosing. Because steady-state AUC 0-12 (0.347 _+0. I 19 ng 9 hr/mL) was similar to single-dose AUC 0-infinity (0.465 _ 0.216 ng 9 hr/mL), epinastine pharmacokinetics are inferred to be linear. There were no study drug-related adverse events nor any clinically relevant changes in visual acuity, biomicroscopy, ophthalmoscopy, vital signs, physical examination, or laboratory parameters. C O N C L U S I O N S : Epinastine HCI 0.05% ophthalmic solution was extremely safe and very well tolerated, rapidly reaching high levels at the ocular surtb.ce, the site of ocular allergy pathology, while minimizing the possibility of unwanted systemic side effects.
Funding: Sell,funded
Funding: AIlergan Inc
Funding: Self-fanded
74 ChronicUrticaria and Helicobacler Pylori Positive Gastritis
75 AnwithEnvironmental Study of Ophthalmic Epinastine in Patients Allergic Conjunctivitis M. A. Abelson ], P. Ghosh 2, R. Bradford 3, B. Kim 3, R. Schiffman 3, S. Whitcup3; 1Ophthalmology Department, Schepens Eye Research Institute, Boston, MA, ZMedical Affairs R&D, Allergan Ltd, High Wycombe, UNITED KINGDOM, 3Ophthalmology Clinical Research, Allergan, lnc, lrvine, CA. RATIONALE: Efficacy and safety evaluation of epinastine HCI 0.05% ophthalmic solution in seasonal allergic conjunctivitis (SAC) patients under environmental conditions. METHODS: Patients (9-71 years) diagnosed with SAC and testing positive in a conjunctival allergen challenge using grass pollens were accepted in this randomized, double-masked, parallel-group, vehicle- and activecontrolled clinical trial. They instilled 1 drop of epinastine HC1 0.05% ophthalmic solution (n = 118), levocabastine 0.05% ophthalmic suspension in = 118), or vehicle (n = 62) in both eyes b.i.d, for 8 weeks. Patients recorded the severity of ocular itching and hyperemia 3 times daily. Biweekly study visits included ophthalmic and visual acuity examinations. RESULTS: Mean ocular itching scores measured during two 7 day periods of maximal pollen counts were 0.77 for epinastine, 0.86 for levocabastine, and 0.93 for vehicle (on a scale of 0 = absent to 4 = extremely severe). Median scores were 0.45, 0.60, and 0.85, respectively. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P = .045). Compared to levocabastine, epinastine was at least as effective for control of ocular itch and hyperemia, No clinically or statistically significant differences in biomicroscopy findings. changes in visual acuity from baseline, or adverse events were observed between treatment groups. CONCLUSIONS: Epinastine 0.05% b.i.d, eye drops were superior to vehicle and equivalent to or better than levocabastine for control of ocular
1"7
The Efficacy of Immunotherapy (IT)in Treatment of Allergic
U / Jr Conjunctivitis(AC): A Meta-Analysis
A, M o n g i a I, L. Bielory2; IDivison o f AHergy & Immunology, Department of Medicine, UMDNJ NJ Medical School, Newark, N J, 2Department of Medicine, UMDNJ NJ Medical School, Newark, NJ. RATIONALE: To understand the role of IT in AC management. METHODS: A literature search was preformed with Medline, PubMed, and Ovid (keywords: AC, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), IT, treatment, allergic rhinitis CAR) and rhinoconjunctivitis (ARC)). IT studies for AR or ARC that assessed subjective (symptom improvement) or objective (medication use, conjunctival provocation testing) ocular endpoints were included. Pharmacotherapy investigations for AR or ARC were excluded. RESULTS: The routes of IT administration noted include local conjunctival (n=2), sublingual (n=6), subcutaneous (n=5), enteric coated capsule (n=l), and intranasal (n=l). IT (n=9) treated groups had an improvement in ocular sensitivity, as determined by conjunctival provocation test (CPT) (p values of <0.001-0.04). In one study using LCIT, conjunctival tolerance improved with decreased sensitivity to allergen concentration (from 10 AU/ml to 1000 AU/ml). IT (n=4) was associated with a decrease in medication use (anti-histamine or eye-drops) (p values of 0.005-0.05). A reduction in mean symptoms score and medication ranged from 24-95%. In 6 studies subjective improvement of ocular symptoms (such as redness and tearing) in the IT group were reported based on QOL or diary cards. IT (n=2) was associated with a decrease in inflammatory cell infiltrate (p=0.04) and 1CAM-I (p=0.02) on conjunctival epithelium after conjunctival allergen challenge. CONCLUSIONS: Current data in the literature support that IT has a specific beneficial effect in ocular allergies and may be an additional indication for its use in the management of AC.
tests (SPT) at the first appointment: 90 (53,9%) patients had PU as the only diagnosis and 77 (46,1%) had also asthma, rhinitis or eczema, with the following atopic distribution: positive SPT in PU - 27.7%; positive SPT in PU with associated allergic diseases - 57.1%. These differences were statistically significant (p=0,0001). There were very few reports of symptoms related with food, In conclusion, papular urticaria justified reference to our department of a significant number of patients. Patients with only PU had sensitization prevalence similar to the expected in Portuguese population (about 25%). In the group with associated allergic diseases, the prevalence was similar to the one found in the population with respiratory allergic disease, in the same age group. It's important to point out the absence of association between these clinical entities, allowing the avoidance of useless diagnostic measures and anxiety about allergic risk.
Abstracts
$237
itching. Epinastine 0.05% ophthalmic solution was effective, safe, and well tolerated in patients with seasonal allergic conjunctivitis.
Funding: Allergan lnc
676 Administration Pharmacokinetic and Safety Profile of EpinastineAfter Ocular in Patients with Allergic Conjunctivitis
V. Djuric, M. Bogic; Institute of Allergology and Immunology, Belgrade, YUGOSLAVIA. RATIONALE: Chronic urticaria is a frustrating diagnostic and therapeutic problem, very often without known cause. According to some authors it may be due to Helicobacter pylori infection. METHODS: Ten patients with chronic urticaria and gastric complaints were included in the study. Skin tests with common allergens were negative and laboratory tests did not help to find the cause of urticaria. Gastroduodenoscopy, biopsy of gastric mucosa and urease test were performed. Patients with Helicobacter pylori positive gastritis were treated with omeprazole, amoxicillin and metronidazole for 12 days and followed for 2 months. RESULTS: Helicobacter pylori positive gastritis was found in 8 patients. After the therapy, significant reduction in number of urticarial lesions and reduction in antihistamine therapy was achieved in 5 patients. CONCLUSIONS: Helicobacter pylori positive gastritis may play a role in the development of chronic urticaria in some of the patients.
D. Yu l, P. Ghosh 2, D. Tang-Liu3; lpharmacokinetics Department, Allergan Inc, Irvine, CA. 2Advisor of Medical Ophthalmology, Allergan Ltd, Wycombe, UNITED KINGDOM, 3pharmacokinetics Department, Allergan Inc, Invine, CA. RATIONALE: Epinastine hydrochloride (HCI), a new generation H1 and H2 receptor antagonist with the ability to stabilize mast cells, is being developed as a treatment for allergic conjunctivitis. We determined tear and plasma pharmacokinetics and the safety profile of ophthalmic epinastine. M E T H O D S : In this single-center, open label study, study personnel instilled 1 drop of epinastine HCI 0.05% in both eyes of 14 allergy patients once on day 0, BID through day 6, and TID on day 7. Serial plasma samples were collected on days 0, 1, and 4-7. Tears were collected on day 7. Epinastine concentrations were determined by a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: Epinastine quickly reached high concentration in tears, with Cmax = 27.1 _+46.2/.tg/mL (mean _+ SD) at 2 min post-dose. Plasma concentrations were approximately one million-fold lower, near the lower limit of quantitation (0.0I ng/mL). Cmax values were 0.025 _+0.008 ng/mL after a single dose and 0.042 _+0.014 ng/mL after 5.5 days of BID dosing. Because steady-state AUC 0-12 (0.347 _+0. I 19 ng 9 hr/mL) was similar to single-dose AUC 0-infinity (0.465 _ 0.216 ng 9 hr/mL), epinastine pharmacokinetics are inferred to be linear. There were no study drug-related adverse events nor any clinically relevant changes in visual acuity, biomicroscopy, ophthalmoscopy, vital signs, physical examination, or laboratory parameters. C O N C L U S I O N S : Epinastine HCI 0.05% ophthalmic solution was extremely safe and very well tolerated, rapidly reaching high levels at the ocular surtb.ce, the site of ocular allergy pathology, while minimizing the possibility of unwanted systemic side effects.
Funding: Sell,funded
Funding: AIlergan Inc
Funding: Self-fanded
74 ChronicUrticaria and Helicobacler Pylori Positive Gastritis
75 AnwithEnvironmental Study of Ophthalmic Epinastine in Patients Allergic Conjunctivitis M. A. Abelson ], P. Ghosh 2, R. Bradford 3, B. Kim 3, R. Schiffman 3, S. Whitcup3; 1Ophthalmology Department, Schepens Eye Research Institute, Boston, MA, ZMedical Affairs R&D, Allergan Ltd, High Wycombe, UNITED KINGDOM, 3Ophthalmology Clinical Research, Allergan, lnc, lrvine, CA. RATIONALE: Efficacy and safety evaluation of epinastine HCI 0.05% ophthalmic solution in seasonal allergic conjunctivitis (SAC) patients under environmental conditions. METHODS: Patients (9-71 years) diagnosed with SAC and testing positive in a conjunctival allergen challenge using grass pollens were accepted in this randomized, double-masked, parallel-group, vehicle- and activecontrolled clinical trial. They instilled 1 drop of epinastine HC1 0.05% ophthalmic solution (n = 118), levocabastine 0.05% ophthalmic suspension in = 118), or vehicle (n = 62) in both eyes b.i.d, for 8 weeks. Patients recorded the severity of ocular itching and hyperemia 3 times daily. Biweekly study visits included ophthalmic and visual acuity examinations. RESULTS: Mean ocular itching scores measured during two 7 day periods of maximal pollen counts were 0.77 for epinastine, 0.86 for levocabastine, and 0.93 for vehicle (on a scale of 0 = absent to 4 = extremely severe). Median scores were 0.45, 0.60, and 0.85, respectively. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P = .045). Compared to levocabastine, epinastine was at least as effective for control of ocular itch and hyperemia, No clinically or statistically significant differences in biomicroscopy findings. changes in visual acuity from baseline, or adverse events were observed between treatment groups. CONCLUSIONS: Epinastine 0.05% b.i.d, eye drops were superior to vehicle and equivalent to or better than levocabastine for control of ocular
1"7
The Efficacy of Immunotherapy (IT)in Treatment of Allergic
U / Jr Conjunctivitis(AC): A Meta-Analysis
A, M o n g i a I, L. Bielory2; IDivison o f AHergy & Immunology, Department of Medicine, UMDNJ NJ Medical School, Newark, N J, 2Department of Medicine, UMDNJ NJ Medical School, Newark, NJ. RATIONALE: To understand the role of IT in AC management. METHODS: A literature search was preformed with Medline, PubMed, and Ovid (keywords: AC, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), IT, treatment, allergic rhinitis CAR) and rhinoconjunctivitis (ARC)). IT studies for AR or ARC that assessed subjective (symptom improvement) or objective (medication use, conjunctival provocation testing) ocular endpoints were included. Pharmacotherapy investigations for AR or ARC were excluded. RESULTS: The routes of IT administration noted include local conjunctival (n=2), sublingual (n=6), subcutaneous (n=5), enteric coated capsule (n=l), and intranasal (n=l). IT (n=9) treated groups had an improvement in ocular sensitivity, as determined by conjunctival provocation test (CPT) (p values of <0.001-0.04). In one study using LCIT, conjunctival tolerance improved with decreased sensitivity to allergen concentration (from 10 AU/ml to 1000 AU/ml). IT (n=4) was associated with a decrease in medication use (anti-histamine or eye-drops) (p values of 0.005-0.05). A reduction in mean symptoms score and medication ranged from 24-95%. In 6 studies subjective improvement of ocular symptoms (such as redness and tearing) in the IT group were reported based on QOL or diary cards. IT (n=2) was associated with a decrease in inflammatory cell infiltrate (p=0.04) and 1CAM-I (p=0.02) on conjunctival epithelium after conjunctival allergen challenge. CONCLUSIONS: Current data in the literature support that IT has a specific beneficial effect in ocular allergies and may be an additional indication for its use in the management of AC.