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Topically applied tacrolimus ointment in pediatric atopic dermatitis patients: Results of a large open-label study
S160 A b s t r a c t s
70Topically Applied Tacrolimus Ointment in Pediatric Atopic Dermatitis Patients: Results of a Large Open-Label Study Lynda Schneider*, Robert Roberts§, William Berger~, Bruce M Prenner~ *Childrens' Hospital/Harvard Meidcal School, Boston, MA §UCLA, Los Angeles, CA ¥Southern California Research, Mission Viejo, CA ~Allergy Associates Medical Group, Incorporated, San Diego, CA OBJECTIVE: To evaluate the safety of tacrolimus ointment when used twice daily, continuously or intermittently, in pediatric patients with atopic dermatitis. METHODS: Male and female patients greater than 2 years of age with atopic dermatitis were enrolled into this open-label, noncomparative study at 150 investigative sites. Patients/parents were instructed to apply 0.03% or 0.1% tacrolimus ointment to all affected areas twice daily. If clearing occurred, treatment continued for 1 week. If the signs and symptoms of atopic dermatitis recurred after cleating, treatment was restarted as directed by the investigator. Assessments occurred at Baseline/Day 1, Month 1, Month 3 and every three months until the end of study. Safety evaluations included adverse events that were reported or observed during the study. RESULTS: A total of 7,978 patients were enrolled into the study. The median study duration was 89 days (range 1-401 days). At the time of the cut-off date for data collection, a total of 1,941 pediatric patients (age 2-15 years) had received at least one application of study drug, were evaluable for safety, and had data submitted for analysis. This includes 1,069 patients 2-6 years of age and 872 patients 7-15 years of age. Slightly more than half (52%) of the pediatric patients were female, 17% were African-American and 11% were Asian. The mean age in the 2-6 year group was 3.7 years (range 2-6) and the mean age in the 7-15 year group was 10.3 years (range 7-15). The mean %BSA affected at baseline for both groups combined was 37% (range 0.2-100.0), with a majority of the patients rated at baseline with severe disease (57%). All adverse events, irrespective of causality to study drug, were reported. The three most common adverse events were flu-like symptoms including cold, influenza and upper respiratory tract infection (19%), skin burning (17%) and pruritus (15%). The skin burning and pruritus were mostly drug related, transient in nature, and decreased in prevalence with clinical improvement. The incidence of flu-like symptoms was somewhat greater among the 2-6 year old group (21%) compared with the 7-15 year old group (17%). This age-effect incidence is in the range of what one might expect in the general pediatric population. CONCLUSION: The adverse event profile of this large study did not reveal safety concerns in the application of tacrolimus ointment in pediatric atopic dermatitis patients between 2-15 years of age. Topically applied tacrolimus ointment is a safe treatment for atopic dermatitis in pediatric patients.
471
Long-Term Safety of Topically Applied Tacrolimus Ointment in Adult Atepic Dermatitis Patients
Mark Boguniewicz*, Donald Ym Leung*, Guy F Webster§, M Joyce Rico¥ *National Jewish Medical and Research Center, Denver, CO §Jefferson Medical College, Philadelphia, PA YFujisawa Healthcare, Incorporated, Deerfield, IL OBJECTIVE: To evaluate the long-term safety of 0.1% tacrolimus ointment in adult atopic dermatitis patients. METHODS: This was an open-label, non-comparative, multicenter extension study. Male and female adults greater than 16 years of age who had not discontinued their participation in a previous tacrolimus ointment study due to a drug-related adverse event or non-compliance were allowed to participate. Patients applied 0.1% tacrolimus ointment twice daily, continuously or intermittently, when disease was present and for one week after clearing. Assessments occurred at Baseline/Day 1, Week 1, and every 3 months during treatment. Observed and treated adverse events were
J ALLERGY CLIN IMMUNOL JANUARY 2002
recorded during the course of the study, with all patients who received at least one application of study drug included in the safety analysis. RESULTS: A total of 407 adults patients with a mean age of 40.1 years (range 16-81) participated in the study for up to three years; over a third (38%, 155) of the patients completed at least 2 years on study. Fifty-two percent were male and 18% were African-American. At the time of enrollment into the study, the mean BSA affected was 34%; 95% of the patients had moderate (53%) or severe (42%) atopic dermatitis. The following are raw incidence rates for the entire study period to date. The incidence of all adverse events over time showed no indication of an increased risk for any adverse event, including infections, with long-term use of tacrolimus ointment for up to 3 years. Overall, the two most common infections were flulike symptoms (common cold, influenza, respiratory tract infection, etc.) (23%) and skin infection (13%). The skin infection category encompasses all skin infections other than herpes simplex (6%), pustular rash (4%), dermatophytosis (4%), folliculitis (4%), warts (1%) and herpes zoster (1%). The incidence of these events in atopic dermatitis patients is consistent with that reported in the literature. Hazard rate analyses also demonstrate no increased risk of infection or other adverse events with long-term use of tacrolimus ointment. CONCLUSION: Tacrolimus ointment 0.1% is safe in the long-term treatment of atopic dermatitis in adult patients.
" 7 ~ The Effects of Montelukast on Atopic Dermatitis lAD): A Place~-- bo-Controlled, Double-Blind. Parallel Study
4l
Timothy J Craig, Christine Correale, Vern Chinchilli, Erik Lehman, Cathy Mende, Amy Longernecker, Jan Light, Jolene Sponhower, James Marks Penn State University College of Medicine, Hershey, PA BACKGROUND: Leukotrienes are important in the pathogenesis of asthma and rhinitis. Montelukast has been shown to be effective in both diseases. Studies have suggested that leukotrienes are involved in the pathogenesis of AD. We performed this protocol to determine if inhibition of the leukotriene cascade would affect the severity of AD. OBJECTIVE: To determine if a leukotriene receptor antagonist is effective as a therapeutic intervention for atopic dermatitis. METHODS: 60 subjects with moderate to severe atopic dermatitis were randomized into a double-blind, placebo-controlled, parallel-study, to receive placebo or montelukast 10 mg each day for 8 weeks. Daily use of a lubricant and a bed time antihistamine (hydroxyzine) were started at recruitment. All other medications were prohibited during the trial. Baseline was established 2 weeks later at randomization. SCORAD, global assessment, daily diary and rash severity scoring were assessed. RESULTS: With the instruments we used there was not a statistical difference noted in the atopic dermatitis between those treated with montelukast compared to placebo; however, there was a positive trend suggesting benefit of montelukast in the pediatric subset. CONCLUSION: Montelukast is effective for the treatment of asthma; however, the role in concomitant allergic skin disorders remains unclear.
~ Fexofenafline Is Effective at Reducing Itching Associated With Atopic Dermatitis 4 'JF~II Makoto Kawashima*, Hidemi Nakagawa§, Toshiro Tango¥, Shotaro Harada(E, Tomoo Noguch&, Masahito lnagi<, *Tokyo Women's Medical University, Tokyo, Japan §Jichi Medical School Hospital, Tokyo, Japan YThe Institute of Public Health, Tokyo, Japan ~Kanto Medical Center NTT, Tokyo, Japan <
70Topically Applied Tacrolimus Ointment in Pediatric Atopic Dermatitis Patients: Results of a Large Open-Label Study Lynda Schneider*, Robert Roberts§, William Berger~, Bruce M Prenner~ *Childrens' Hospital/Harvard Meidcal School, Boston, MA §UCLA, Los Angeles, CA ¥Southern California Research, Mission Viejo, CA ~Allergy Associates Medical Group, Incorporated, San Diego, CA OBJECTIVE: To evaluate the safety of tacrolimus ointment when used twice daily, continuously or intermittently, in pediatric patients with atopic dermatitis. METHODS: Male and female patients greater than 2 years of age with atopic dermatitis were enrolled into this open-label, noncomparative study at 150 investigative sites. Patients/parents were instructed to apply 0.03% or 0.1% tacrolimus ointment to all affected areas twice daily. If clearing occurred, treatment continued for 1 week. If the signs and symptoms of atopic dermatitis recurred after cleating, treatment was restarted as directed by the investigator. Assessments occurred at Baseline/Day 1, Month 1, Month 3 and every three months until the end of study. Safety evaluations included adverse events that were reported or observed during the study. RESULTS: A total of 7,978 patients were enrolled into the study. The median study duration was 89 days (range 1-401 days). At the time of the cut-off date for data collection, a total of 1,941 pediatric patients (age 2-15 years) had received at least one application of study drug, were evaluable for safety, and had data submitted for analysis. This includes 1,069 patients 2-6 years of age and 872 patients 7-15 years of age. Slightly more than half (52%) of the pediatric patients were female, 17% were African-American and 11% were Asian. The mean age in the 2-6 year group was 3.7 years (range 2-6) and the mean age in the 7-15 year group was 10.3 years (range 7-15). The mean %BSA affected at baseline for both groups combined was 37% (range 0.2-100.0), with a majority of the patients rated at baseline with severe disease (57%). All adverse events, irrespective of causality to study drug, were reported. The three most common adverse events were flu-like symptoms including cold, influenza and upper respiratory tract infection (19%), skin burning (17%) and pruritus (15%). The skin burning and pruritus were mostly drug related, transient in nature, and decreased in prevalence with clinical improvement. The incidence of flu-like symptoms was somewhat greater among the 2-6 year old group (21%) compared with the 7-15 year old group (17%). This age-effect incidence is in the range of what one might expect in the general pediatric population. CONCLUSION: The adverse event profile of this large study did not reveal safety concerns in the application of tacrolimus ointment in pediatric atopic dermatitis patients between 2-15 years of age. Topically applied tacrolimus ointment is a safe treatment for atopic dermatitis in pediatric patients.
471
Long-Term Safety of Topically Applied Tacrolimus Ointment in Adult Atepic Dermatitis Patients
Mark Boguniewicz*, Donald Ym Leung*, Guy F Webster§, M Joyce Rico¥ *National Jewish Medical and Research Center, Denver, CO §Jefferson Medical College, Philadelphia, PA YFujisawa Healthcare, Incorporated, Deerfield, IL OBJECTIVE: To evaluate the long-term safety of 0.1% tacrolimus ointment in adult atopic dermatitis patients. METHODS: This was an open-label, non-comparative, multicenter extension study. Male and female adults greater than 16 years of age who had not discontinued their participation in a previous tacrolimus ointment study due to a drug-related adverse event or non-compliance were allowed to participate. Patients applied 0.1% tacrolimus ointment twice daily, continuously or intermittently, when disease was present and for one week after clearing. Assessments occurred at Baseline/Day 1, Week 1, and every 3 months during treatment. Observed and treated adverse events were
J ALLERGY CLIN IMMUNOL JANUARY 2002
recorded during the course of the study, with all patients who received at least one application of study drug included in the safety analysis. RESULTS: A total of 407 adults patients with a mean age of 40.1 years (range 16-81) participated in the study for up to three years; over a third (38%, 155) of the patients completed at least 2 years on study. Fifty-two percent were male and 18% were African-American. At the time of enrollment into the study, the mean BSA affected was 34%; 95% of the patients had moderate (53%) or severe (42%) atopic dermatitis. The following are raw incidence rates for the entire study period to date. The incidence of all adverse events over time showed no indication of an increased risk for any adverse event, including infections, with long-term use of tacrolimus ointment for up to 3 years. Overall, the two most common infections were flulike symptoms (common cold, influenza, respiratory tract infection, etc.) (23%) and skin infection (13%). The skin infection category encompasses all skin infections other than herpes simplex (6%), pustular rash (4%), dermatophytosis (4%), folliculitis (4%), warts (1%) and herpes zoster (1%). The incidence of these events in atopic dermatitis patients is consistent with that reported in the literature. Hazard rate analyses also demonstrate no increased risk of infection or other adverse events with long-term use of tacrolimus ointment. CONCLUSION: Tacrolimus ointment 0.1% is safe in the long-term treatment of atopic dermatitis in adult patients.
" 7 ~ The Effects of Montelukast on Atopic Dermatitis lAD): A Place~-- bo-Controlled, Double-Blind. Parallel Study
4l
Timothy J Craig, Christine Correale, Vern Chinchilli, Erik Lehman, Cathy Mende, Amy Longernecker, Jan Light, Jolene Sponhower, James Marks Penn State University College of Medicine, Hershey, PA BACKGROUND: Leukotrienes are important in the pathogenesis of asthma and rhinitis. Montelukast has been shown to be effective in both diseases. Studies have suggested that leukotrienes are involved in the pathogenesis of AD. We performed this protocol to determine if inhibition of the leukotriene cascade would affect the severity of AD. OBJECTIVE: To determine if a leukotriene receptor antagonist is effective as a therapeutic intervention for atopic dermatitis. METHODS: 60 subjects with moderate to severe atopic dermatitis were randomized into a double-blind, placebo-controlled, parallel-study, to receive placebo or montelukast 10 mg each day for 8 weeks. Daily use of a lubricant and a bed time antihistamine (hydroxyzine) were started at recruitment. All other medications were prohibited during the trial. Baseline was established 2 weeks later at randomization. SCORAD, global assessment, daily diary and rash severity scoring were assessed. RESULTS: With the instruments we used there was not a statistical difference noted in the atopic dermatitis between those treated with montelukast compared to placebo; however, there was a positive trend suggesting benefit of montelukast in the pediatric subset. CONCLUSION: Montelukast is effective for the treatment of asthma; however, the role in concomitant allergic skin disorders remains unclear.
~ Fexofenafline Is Effective at Reducing Itching Associated With Atopic Dermatitis 4 'JF~II Makoto Kawashima*, Hidemi Nakagawa§, Toshiro Tango¥, Shotaro Harada(E, Tomoo Noguch&, Masahito lnagi<, *Tokyo Women's Medical University, Tokyo, Japan §Jichi Medical School Hospital, Tokyo, Japan YThe Institute of Public Health, Tokyo, Japan ~Kanto Medical Center NTT, Tokyo, Japan <