Tolerability and efficacy of Azelastine eye drops in the treatment of allergic conjunctivitis, large scale experience in

1. Tolerability and efficacy of Azelastine eye drops in the treatment of allergic conjunctivitis, large scale experience in community practice • Ralph Mösges *,W. Pütz**, C. Diez Crespo***, Martin Bähre**** • *Medical Faculty University of Cologne, Germany, **KliFo Aachen, Germany • ***ASTA Medica S.A.U. Coslada, Spain, ****ASTA Medica AG Frankfurt, Germany The study population Initial eye drop dosage Time until onset of action Relief of symptoms Percent Time (min.) Length of the post-marketing survey Duration of action February 1999 - October 1999 Azelastine eye drops have been registered for the treatment of allergic conjunctivitis throughout Europe and are marketed in Austria, the Baltic States, Belgium, Bulgaria, France, Germany, Great Britain, Ireland, Italy, the Netherlands, Portugal, Spain, and Russia. The objective of this post-marketing survey was primarily to establish the safety of Azelastine eye drops in the dosage of two drops/eye/day on a large scale under practical conditions. In addition, data were retrieved as to efficacy in an unselected patient population. 3000 patients with allergic conjunctivitis were to be observed during a two-week therapy period. The questionnaires for 1647 patients were received on time. 54.7% of the patients were female, and the average age was 31.0 years. Concomitant diseases or disorders were answered with yes in 61.9% (1020) of the cases, but the questions as to ”Rhinitis allergica” received 1013 affirmative answers, ”Conjunctivitis vernal” 204, and ”others” received 208. Of the ”other” responses, asthma dominated in 183 patients as the most frequent concomitant disease. The medical history of allergic conjunctivitis was given to be on average 4.0 years ± 5.0; the minimum was one day, and the maximum was 40 years. Prior treatment had been received in 55.3% (912) of the cases, of which oral antihistamines (654), cromoglycate eye drops (240), levocabastine eye drops (224), and nedocromil eye drops (147) were the most commonly used medications in prior treatment. Main endpoint criteria were the courses of the severity of the eight ocular clinical symptoms of itching, redness, tearing, eyelid swelling, sensation of a foreign body in the eye, photophobia, pain, and sticky eyelids, which usually occur in allergic conjunctivitis, and the four nasal clinical symptoms of itching, sneezing, rhinorrhea, and stuffy nose. There was a clear improvement for all symptoms. Azelastine eye drops proved to be particularly effective in relieving the symptoms ”ocular itching” with an improvement rate of 90.8% (1447) [freedom from symptoms rate 45.0% (712)], ”tearing” at an improvement rate of 85.4% (1333) [freedom from symptoms 61.6% (962)], and ”eye redness” at a rate of 84.5% (1316) improvement [freedom from symptoms 58.2% (907)]. For the symptoms ”ocular pain” there was a 75.4% (1154) improvement [freedom from symptoms 48.8% (747)], for ”sensation of a foreign body in the eye” a 67.4% (1039) improvement [freedom from symptoms 51.9% (800)], and for ”photophobia” 64.5% (994) improvement [freedom from symptoms 50.4% (776)]. The ocular symptoms ”sticky eyelids” and ”eyelid swelling” showed the poorest improvement rates of 51.1% (764) [freedom from symptoms 44.6% (668)] and 50.6% (770) [freedom from symptoms 43.4% (660)] respectively. Thus, a freedom from symptoms was observed for the ocular symptoms in 44.6% to 61.6% of the patients, an improvement of the symptoms in 50.6% to 90.8% of the patients, and a worsening of symptoms and thus no effectiveness of the therapy was documented in only 0.5% to 2.1% of the patients. The nasal symptoms showed nearly the same improvement rates under therapy with Azelastine eye drops. For the symptom ”nasal itching” the improvement rate was 58.5% (867) [freedom from symptoms 31.2% (463)], ”sneezing” showed an improvement rate of 57.2% (853) [freedom from symptoms 31.6% (472)], ”rhinorrhea”improved in 55.8% (831) [freedom from symptoms 33.9% (505)], and ”stuffy nose” in 54.8% (813) [freedom from symptoms 31.1% (461)] of the patients. For the nasal symptoms the freedom from symptoms rate was 31.1% to 33.9% and the improvement rate was 54.8% to 58.5%. A worsening of the symptoms occurred in no more than 2.4% of the patients. The recommended dosage of two drops/eye/day was followed by 68.4% of the investigating physicians, while 4.8% reported giving an initial dosage of one drop/eye/day. The remaining dosages reported were higher. The maximum dosage reported was 12 drops/eye/day. During the course of therapy an adjustment of the dosage or a change in the length of treatment was undertaken in 204 patients. Of those cases, the dosage was increased in 42 cases and decreased in 65 patients; the length of treatment was adjusted in 97 cases. A second change in the dosage was necessary for 30 patients, of which 14 patients’ dosages were raised and 4 patients’ dosages were lowered, in comparison to the first adjustment. Concomitant medication for allergic conjunctivitis was taken by 404 patients (24.5%), while 751 patients (45.6%) took 1014 concomitant medications for other diseases. In the pharmacokinetic evaluation, time periods of 1 to 240 min resulted for the time until onset of action, on the average 19.1 (±16.2) minutes, and time periods of 0.1 to 80 hours for the duration of action, on the average 9.6 (±4.5) hours. When the patients were questioned about their satisfaction with Azelastineeye drops at the end of the treatment period, 90.3% (1488) of the patients stated that they were satisfied with the eye drops, and only 4.7% (78) of the patients were dissatisfied. The reason for particular satisfaction with the medication was rapid onset of action for 1171 patients and simple handling for 852 patients. 147 patients (8.9%) named other reasons for their particular satisfaction with Azelastine eye drops besides the given reasons; most common were good tolerability, efficacy, and the absence of uncomfortable concomitant side effects such as pain or a burning sensation when applying the eye drops. The quality of life was considered to have improved by 83.8% (1381) of the patients during the course of treatment. Under therapy with Azelastine eye drops, everyday activities such as ”work” were judged to be possible without limitations by 45.2% (without drops in 19.7%) of the patients, ”walking outdoors ” by 65.3% (without 8.9%), ”sleeping with the window open” by 43.5% (without 16.5%), and ”exercise outdoors” by 56.2% (without 9.7%) of the patients. 77 patients (4.6%) stated further activities such as riding a motorcycle, swimming, going to the movies, watching TV, wearing contact lenses, attending school or studying, wearing makeup, etc. Discontinuation of treatment was documented in 25.9% (427) of the patients. The treatment is being continued in 66.1% (1089) of the cases. The reasons stated for stopping treatment were the absence of symptoms (383), ineffectiveness of treatment (51), lack of compliance (19), and occurrence of adverse events in 11 cases. Adverse events were documented in 3.9% (65) of the observed cases; mild pain and irritation of the eye, bitter taste, burning and itching during use were the most common adverse events. The efficacy of the treatment was confirmed by the majority of patients and physicians. 90.6% of the physicians and 89.6% of the patients claimed treatment success; only 5.3% of the physicians and 6.4% of the patients documented dissatisfaction with the effectiveness of Azelastine eye drops, and 0.9% and 0.6% respectively did not consider the assessable. The physicians judged the tolerability of the treatment to be ”very good – good” in 57.1% of the cases and ”satisfactory” in 35.8% of the cases. The tolerability is described as ”not satisfactory” in only 1.2% of the cases. 53.1% of the patients judged the tolerability to be ”very good – good,” 38.8% of the patients considered it to be ”satisfactory,” and 1.8% of the patients assessed the tolerability as ”not satisfactory.” Dosage 1 drop of Allergodil® eye drops in each eye twice daily (mornings and evenings) Mean onset of action 0.33 hours Mean duration of action 9.6 hours Global assessment of efficacy by the patients Satisfaction with Allergodil® eye drops Global assessment of efficacy by the investigating physicians Particular satisfaction with Allergodil® eye drops Global assessment of tolerability by the patients Efficacy comparison between Allergodil® eye drops and others Global assessment of tolerability by the investigating physicians Occurrence of adverse events Study performed by the German Rhinitis Study Group www.rhinitis.de