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Long-term safety and efficacy of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea
5368
4867
Long-term safety and efficacy of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea Zoe Diana Draelos, MD, Dermatology Consulting Services; Michael H. Gold, MD, Gold Skin Care Center; Robert A. Weiss, MD, Laser Skin & Vein Institute; Leslie Baumann, MD, Baumann Cosmetic & Research Institute, Inc; Steven K. Grekin, MD, Grekin Skin Institute; Deanna Mraz Robinson, MD, Connecticut Dermatology Group; David R. Berk, MD, Allergan Plc; Gurpreet Ahluwalia, PhD, Allergan Plc Introduction: Two phase 3 pivotal trials demonstrated the efficacy and safety of oxymetazoline, a specific a1A-adrenoceptor agonist, for treatment of moderate to severe persistent facial erythema associated with rosacea. The current study examined the safety and efficacy of long-term oxymetazoline treatment in patients with this chronic dermatologic condition. Methods: In this multicenter, open-label trial, eligible patients topically applied oxymetazoline hydrochloride cream 1.0% (oxymetazoline) once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, Clinician Telangiectasia Assessment, dermal tolerability, and rebound erythema following treatment cessation based on Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA). Efficacy was assessed based on the proportion of patients achieving response ($2 grade improvement in severity from baseline) on CEA and SSA at 3 and 6 hours postdose at weeks 4, 26, and 52. Results: A total of 440 eligible patients were enrolled (mean age: 53.1 years; 76.1% females); most had moderate erythema (CEA: 76.6%; SSA: 88.4%). The incidence of treatment-related TEAEs was low (8.2%), most were mild or moderate in severity, and the most common were application-site dermatitis (1.8%), paresthesia (1.6%), pain (1.1%), and pruritus (1.1%). Discontinuations due to TEAEs were low (3.2%) and mostly due to application-site dermatitis (1.4%). The incidence of serious TEAEs was 3.4%; the most common was basal cell carcinoma (1.4%); none were treatment related or led to study discontinuation. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, low proportions of patients exhibited $1-grade worsening of patient-reported itching (3.7%) and burning/stinging (5.1%) and physician-rated dryness (9.3%) and scaling (6.1%). At week 4, 19.5% and 23.0% of patients, respectively, achieved $2-grade improvement in CEA and SSA at 3 and 6 hours postdose; 36.7% and 43.4%, respectively, achieved response at week 52. No apparent rebound effect was observed following treatment cessation (week 52, before last dose: 0.7%; week 54: 0.7%).
Low risk of bleeding complications in diagnostic skin biopsies performed on thrombocytopenic inpatients Fan Di Xia, BA, Brigham and Women’s Hospital; Harvard Medical School; Hasan Khosravi, BS, Harvard Medical School; Michael Waul, BA, Harvard Medical School; Daniel Butler, MD, Brigham and Women’s Hospital; Cara Joyce, PhD, Loyola University Chicago; Arash Mostaghimi, MD, Brigham and Women’s Hospital Guidelines for performing skin biopsies in patients with thrombocytopenia are highly variable, and data on bleeding risk after diagnostic skin biopsy in thrombocytopenic patients are limited. In this study, we evaluate the risk of bleeding after skin biopsies in patients with thrombocytopenia and other bleeding risk factors. We reviewed the records of 205 thrombocytopenic (platelets \ 150,000/L) patients who underwent diagnostic skin biopsies as an inpatient at the Brigham and Women’s Hospital and Massachusetts General Hospital from 20002015. We identified one case of bleeding, which consisted of oozing from a punch biopsy site that was left to heal by secondary intent. The bleeding risk of 1 out of 205 (0.49%) was not statistically different than the literature data for bleeding complications rate in non-thrombocytopenic patients, which was reported at 0% (0 out of 100 biopsies) (P ¼.48). None of the 75 patients with platelets # 20,000/L in our study had bleeding complications. 44 (21.5%) patients were on anticoagulation/antiplatelet agents at the time of biopsy, and 6 (2.9%) patients had had recent active bleeding. These results suggest that bleeding risk is low even in high-risk thrombocytopenic patients. This finding should reduce physician discomfort regarding performing skin biopsies in thrombocytopenic patients, reduce variability regarding platelet threshold above which to perform skin biopsies, and eliminate unnecessary platelet transfusions for thrombocytopenic patients prior to biopsy. Commercial support: None identified.
Conclusion: Topical oxymetazoline showed consistent safety, tolerability, and efficacy over 52 weeks in patients with persistent facial erythema associated with rosacea. There was no apparent rebound effect following cessation of oxymetazoline treatment. Commercial support: None identified.
5390 4927 Long-term safety of apremilast treatment in psoriasis and psoriatic arthritis patients: pooled analysis for 156 weeks and beyond in the ESTEEM 1 and 2 and PALACE 1-3 phase 3 trials Jeffrey Crowley, MD, Bakersfield Dermatology; J€ urgen Wollenhaupt, MD, Sch€ on Klinik Hamburg Eilbek; Kristian Reich, MD, SCIderm Research Institute and Dermatologikum; Kamal Shah, MD, Bio-Pharma Life Cycle Management LLC; Rongdean Chen, PhD, Celgene Corporation; Philip J. Mease, MD, Swedish Medical Center and University of Washington School of Medicine Background: Apremilast, an oral phosphodiesterase 4 inhibitor, has shown efficacy in phase 3 randomized, placebo (PBO)-controlled trials in patients (pts) with moderate to severe plaque psoriasis (ESTEEM 1 and 2) and active psoriatic arthritis (PsA; PALACE 1-3). We report safety and tolerability of apremilast 30 mg BID (APR) in a pooled analysis of these 5 studies. Methods: Safety findings for PBO vs APR are reported for 0 to 16 wks and the overall APRexposure period (0 to $156 wks) for pts receiving APR at any time during the study through February 2015; 30.2% (n ¼ 575) of pts had[3 yrs ([156 wks) of APR exposure. Results: 2,242 pts were included in the safety analysis for 0 to 16 wks (PBO n ¼ 913; APR n ¼ 1,329); 1,905 pts received APR for 0 to $156 wks. At baseline, 64.2% of APR pts in PALACE 1-3 were receiving concomitant DMARDs, including methotrexate. During 0 to 16 wks, rates of severe or serious adverse events (AEs) with APR were low and comparable to PBO. Common AEs ($5% of pts) with APR during 0 to 16 wks were diarrhea (15.3%), nausea (13.2%), headache (6.5%), upper respiratory tract infection (6.8%), and nasopharyngitis (5.4%). Most cases of diarrhea and nausea were mild to moderate in severity, occurred during the first 2 wks of APR exposure, and generally resolved in 1 month. During the overall APR-exposure period (3,527.5 pt-yrs), the exposure-adjusted incidence rates (EAIR)/100 pt-yrs for AEs, serious AEs, and discontinuations due to AEs did not increase with increasing cumulative exposure; this is confirmed by assessment of rates on a yr-by-yr exposure basis. The EAIR/100 pt-yrs of MACE, malignancies, and serious infections in pts receiving APR were comparable to PBO during 0 to16 wks and remained low with prolonged APR exposure. No serious opportunistic infections or clinically meaningful effects on laboratory parameters were reported. EAIR/100 pt-yrs for depression did not increase with prolonged APR exposure relative to the 0 to #52 wk APR-exposure period (1.4 vs 2.1). Weight loss in pts receiving APR did not lead to any overt medical sequelae through the APR-exposure period. Mean percent change from baseline weight was 1.32% for the overall APR-exposure period. Conclusions: APR demonstrated an acceptable safety profile, and tolerability improved with prolonged exposure for $156 wks. No new safety signals were observed with long-term APR treatment in pts with moderate to severe plaque psoriasis and PsA. Commercial support: 100% is sponsored by Celgene Corporation.
Low serious infection rates in patients with psoriasis and psoriatic arthritis treated with apremilast for 156 weeks and beyond: Pooled analysis of the phase 3 ESTEEM 1 and 2 and PALACE 1-3 trials David M. Pariser, MD, Eastern Virginia Medical School and Virginia Clinical Research, Inc.; Juan J. Gomez-Reino, MD, Hospital Clınico Universitario; Ketty Peris, MD, Catholic University of Rome; Kamal Shah, MD, Bio-Pharma Life Cycle Management LLC; Rongdean Chen, PhD, Celgene Corporation; Arthur Kavanaugh, MD, University of California, San Diego Background: Apremilast is an oral phosphodiesterase 4 inhibitor shown to be effective in phase 3, randomized, placebo (PBO)-controlled trials assessing treatment of moderate to severe plaque psoriasis (ESTEEM 1 and 2) and active psoriatic arthritis (PsA; PALACE 1-3). We report incidence of serious infections (SIs; opportunistic and non-opportunistic) in patients (pts) receiving apremilast 30 mg BID (APR) for $156 wks in a pooled analysis of these studies. Methods: Exposure-adjusted incidence rates (EAIR)/100 pt-yrs of SIs and serious opportunistic infections (SOIs) with PBO vs APR are reported for 0 to 16 wks, 0 to #52 wks, and the overall APR-exposure period (0 to $156 wks) for pts receiving APR at any time during the study through February 2015; 30.2% of pts (n ¼ 575) had [ 3 yrs ( [ 156 wks) of APR exposure. Results: In total, 2,242 pts were included in the safety analysis for 0 to 16 wks (PBO n ¼ 913 [260.2 pt-yrs]; APR n ¼ 1,329 [377.8 pt-yrs]); 1,905 pts received APR during 0 to #52 wks (1,524.5 pt-yrs) and the overall APR-exposure period (3,527.5 pt-yrs). Of note, 64.2% of pts in the APR group in PALACE 1-3 were receiving concomitant DMARDs (including methotrexate) at baseline. During 0 to 16 wks, rates of SIs with APR were low and comparable to PBO. During 0 to $156 wks, the majority of reported infections were not SIs (eg, upper respiratory tract infection, nasopharyngitis, sinusitis). SI rates were low during 0 to #52 wks (EAIR/100 pt-yrs: 0.7) and 0 to $156 wks (EAIR/100 pt-yrs: 1.0); most SIs occurred in only 1 pt. The rate of SIs occurring in [ 1 pt with prolonged APR exposure was consistent with that expected for these infections in the general US population. SIs occurring in $2 pts included pneumonia, appendicitis, bronchitis, diverticulitis, sepsis, and urinary tract infection. No SOIs or clinical reactivations of tuberculosis (TB) were reported during 0 to 16 wks or 0 to $156 wks in these studies. Discontinuation due to infections was low (\1.0%) and comparable between pts receiving PBO (0.3%) and APR (0.4%) during the 0 to 16 wk period; the EAIR/100 pt-yrs of discontinuations due to infections did not increase with increasing exposure to APR (0 to #52 wks: 0.5; 0 to $156 wks: 0.4). Conclusions: In this pooled analysis, the incidence of SIs was low in pts with psoriasis and PsA receiving APR for $156 wks. No clustering or trends in events, SOIs, or clinical reactivations of TB were observed with prolonged APR treatment in these studies. Commercial support: 100 % is sponsored by Celgene Corporation.
AB162
J AM ACAD DERMATOL
JUNE 2017
4867
Long-term safety and efficacy of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea Zoe Diana Draelos, MD, Dermatology Consulting Services; Michael H. Gold, MD, Gold Skin Care Center; Robert A. Weiss, MD, Laser Skin & Vein Institute; Leslie Baumann, MD, Baumann Cosmetic & Research Institute, Inc; Steven K. Grekin, MD, Grekin Skin Institute; Deanna Mraz Robinson, MD, Connecticut Dermatology Group; David R. Berk, MD, Allergan Plc; Gurpreet Ahluwalia, PhD, Allergan Plc Introduction: Two phase 3 pivotal trials demonstrated the efficacy and safety of oxymetazoline, a specific a1A-adrenoceptor agonist, for treatment of moderate to severe persistent facial erythema associated with rosacea. The current study examined the safety and efficacy of long-term oxymetazoline treatment in patients with this chronic dermatologic condition. Methods: In this multicenter, open-label trial, eligible patients topically applied oxymetazoline hydrochloride cream 1.0% (oxymetazoline) once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, Clinician Telangiectasia Assessment, dermal tolerability, and rebound erythema following treatment cessation based on Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA). Efficacy was assessed based on the proportion of patients achieving response ($2 grade improvement in severity from baseline) on CEA and SSA at 3 and 6 hours postdose at weeks 4, 26, and 52. Results: A total of 440 eligible patients were enrolled (mean age: 53.1 years; 76.1% females); most had moderate erythema (CEA: 76.6%; SSA: 88.4%). The incidence of treatment-related TEAEs was low (8.2%), most were mild or moderate in severity, and the most common were application-site dermatitis (1.8%), paresthesia (1.6%), pain (1.1%), and pruritus (1.1%). Discontinuations due to TEAEs were low (3.2%) and mostly due to application-site dermatitis (1.4%). The incidence of serious TEAEs was 3.4%; the most common was basal cell carcinoma (1.4%); none were treatment related or led to study discontinuation. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, low proportions of patients exhibited $1-grade worsening of patient-reported itching (3.7%) and burning/stinging (5.1%) and physician-rated dryness (9.3%) and scaling (6.1%). At week 4, 19.5% and 23.0% of patients, respectively, achieved $2-grade improvement in CEA and SSA at 3 and 6 hours postdose; 36.7% and 43.4%, respectively, achieved response at week 52. No apparent rebound effect was observed following treatment cessation (week 52, before last dose: 0.7%; week 54: 0.7%).
Low risk of bleeding complications in diagnostic skin biopsies performed on thrombocytopenic inpatients Fan Di Xia, BA, Brigham and Women’s Hospital; Harvard Medical School; Hasan Khosravi, BS, Harvard Medical School; Michael Waul, BA, Harvard Medical School; Daniel Butler, MD, Brigham and Women’s Hospital; Cara Joyce, PhD, Loyola University Chicago; Arash Mostaghimi, MD, Brigham and Women’s Hospital Guidelines for performing skin biopsies in patients with thrombocytopenia are highly variable, and data on bleeding risk after diagnostic skin biopsy in thrombocytopenic patients are limited. In this study, we evaluate the risk of bleeding after skin biopsies in patients with thrombocytopenia and other bleeding risk factors. We reviewed the records of 205 thrombocytopenic (platelets \ 150,000/L) patients who underwent diagnostic skin biopsies as an inpatient at the Brigham and Women’s Hospital and Massachusetts General Hospital from 20002015. We identified one case of bleeding, which consisted of oozing from a punch biopsy site that was left to heal by secondary intent. The bleeding risk of 1 out of 205 (0.49%) was not statistically different than the literature data for bleeding complications rate in non-thrombocytopenic patients, which was reported at 0% (0 out of 100 biopsies) (P ¼.48). None of the 75 patients with platelets # 20,000/L in our study had bleeding complications. 44 (21.5%) patients were on anticoagulation/antiplatelet agents at the time of biopsy, and 6 (2.9%) patients had had recent active bleeding. These results suggest that bleeding risk is low even in high-risk thrombocytopenic patients. This finding should reduce physician discomfort regarding performing skin biopsies in thrombocytopenic patients, reduce variability regarding platelet threshold above which to perform skin biopsies, and eliminate unnecessary platelet transfusions for thrombocytopenic patients prior to biopsy. Commercial support: None identified.
Conclusion: Topical oxymetazoline showed consistent safety, tolerability, and efficacy over 52 weeks in patients with persistent facial erythema associated with rosacea. There was no apparent rebound effect following cessation of oxymetazoline treatment. Commercial support: None identified.
5390 4927 Long-term safety of apremilast treatment in psoriasis and psoriatic arthritis patients: pooled analysis for 156 weeks and beyond in the ESTEEM 1 and 2 and PALACE 1-3 phase 3 trials Jeffrey Crowley, MD, Bakersfield Dermatology; J€ urgen Wollenhaupt, MD, Sch€ on Klinik Hamburg Eilbek; Kristian Reich, MD, SCIderm Research Institute and Dermatologikum; Kamal Shah, MD, Bio-Pharma Life Cycle Management LLC; Rongdean Chen, PhD, Celgene Corporation; Philip J. Mease, MD, Swedish Medical Center and University of Washington School of Medicine Background: Apremilast, an oral phosphodiesterase 4 inhibitor, has shown efficacy in phase 3 randomized, placebo (PBO)-controlled trials in patients (pts) with moderate to severe plaque psoriasis (ESTEEM 1 and 2) and active psoriatic arthritis (PsA; PALACE 1-3). We report safety and tolerability of apremilast 30 mg BID (APR) in a pooled analysis of these 5 studies. Methods: Safety findings for PBO vs APR are reported for 0 to 16 wks and the overall APRexposure period (0 to $156 wks) for pts receiving APR at any time during the study through February 2015; 30.2% (n ¼ 575) of pts had[3 yrs ([156 wks) of APR exposure. Results: 2,242 pts were included in the safety analysis for 0 to 16 wks (PBO n ¼ 913; APR n ¼ 1,329); 1,905 pts received APR for 0 to $156 wks. At baseline, 64.2% of APR pts in PALACE 1-3 were receiving concomitant DMARDs, including methotrexate. During 0 to 16 wks, rates of severe or serious adverse events (AEs) with APR were low and comparable to PBO. Common AEs ($5% of pts) with APR during 0 to 16 wks were diarrhea (15.3%), nausea (13.2%), headache (6.5%), upper respiratory tract infection (6.8%), and nasopharyngitis (5.4%). Most cases of diarrhea and nausea were mild to moderate in severity, occurred during the first 2 wks of APR exposure, and generally resolved in 1 month. During the overall APR-exposure period (3,527.5 pt-yrs), the exposure-adjusted incidence rates (EAIR)/100 pt-yrs for AEs, serious AEs, and discontinuations due to AEs did not increase with increasing cumulative exposure; this is confirmed by assessment of rates on a yr-by-yr exposure basis. The EAIR/100 pt-yrs of MACE, malignancies, and serious infections in pts receiving APR were comparable to PBO during 0 to16 wks and remained low with prolonged APR exposure. No serious opportunistic infections or clinically meaningful effects on laboratory parameters were reported. EAIR/100 pt-yrs for depression did not increase with prolonged APR exposure relative to the 0 to #52 wk APR-exposure period (1.4 vs 2.1). Weight loss in pts receiving APR did not lead to any overt medical sequelae through the APR-exposure period. Mean percent change from baseline weight was 1.32% for the overall APR-exposure period. Conclusions: APR demonstrated an acceptable safety profile, and tolerability improved with prolonged exposure for $156 wks. No new safety signals were observed with long-term APR treatment in pts with moderate to severe plaque psoriasis and PsA. Commercial support: 100% is sponsored by Celgene Corporation.
Low serious infection rates in patients with psoriasis and psoriatic arthritis treated with apremilast for 156 weeks and beyond: Pooled analysis of the phase 3 ESTEEM 1 and 2 and PALACE 1-3 trials David M. Pariser, MD, Eastern Virginia Medical School and Virginia Clinical Research, Inc.; Juan J. Gomez-Reino, MD, Hospital Clınico Universitario; Ketty Peris, MD, Catholic University of Rome; Kamal Shah, MD, Bio-Pharma Life Cycle Management LLC; Rongdean Chen, PhD, Celgene Corporation; Arthur Kavanaugh, MD, University of California, San Diego Background: Apremilast is an oral phosphodiesterase 4 inhibitor shown to be effective in phase 3, randomized, placebo (PBO)-controlled trials assessing treatment of moderate to severe plaque psoriasis (ESTEEM 1 and 2) and active psoriatic arthritis (PsA; PALACE 1-3). We report incidence of serious infections (SIs; opportunistic and non-opportunistic) in patients (pts) receiving apremilast 30 mg BID (APR) for $156 wks in a pooled analysis of these studies. Methods: Exposure-adjusted incidence rates (EAIR)/100 pt-yrs of SIs and serious opportunistic infections (SOIs) with PBO vs APR are reported for 0 to 16 wks, 0 to #52 wks, and the overall APR-exposure period (0 to $156 wks) for pts receiving APR at any time during the study through February 2015; 30.2% of pts (n ¼ 575) had [ 3 yrs ( [ 156 wks) of APR exposure. Results: In total, 2,242 pts were included in the safety analysis for 0 to 16 wks (PBO n ¼ 913 [260.2 pt-yrs]; APR n ¼ 1,329 [377.8 pt-yrs]); 1,905 pts received APR during 0 to #52 wks (1,524.5 pt-yrs) and the overall APR-exposure period (3,527.5 pt-yrs). Of note, 64.2% of pts in the APR group in PALACE 1-3 were receiving concomitant DMARDs (including methotrexate) at baseline. During 0 to 16 wks, rates of SIs with APR were low and comparable to PBO. During 0 to $156 wks, the majority of reported infections were not SIs (eg, upper respiratory tract infection, nasopharyngitis, sinusitis). SI rates were low during 0 to #52 wks (EAIR/100 pt-yrs: 0.7) and 0 to $156 wks (EAIR/100 pt-yrs: 1.0); most SIs occurred in only 1 pt. The rate of SIs occurring in [ 1 pt with prolonged APR exposure was consistent with that expected for these infections in the general US population. SIs occurring in $2 pts included pneumonia, appendicitis, bronchitis, diverticulitis, sepsis, and urinary tract infection. No SOIs or clinical reactivations of tuberculosis (TB) were reported during 0 to 16 wks or 0 to $156 wks in these studies. Discontinuation due to infections was low (\1.0%) and comparable between pts receiving PBO (0.3%) and APR (0.4%) during the 0 to 16 wk period; the EAIR/100 pt-yrs of discontinuations due to infections did not increase with increasing exposure to APR (0 to #52 wks: 0.5; 0 to $156 wks: 0.4). Conclusions: In this pooled analysis, the incidence of SIs was low in pts with psoriasis and PsA receiving APR for $156 wks. No clustering or trends in events, SOIs, or clinical reactivations of TB were observed with prolonged APR treatment in these studies. Commercial support: 100 % is sponsored by Celgene Corporation.
AB162
J AM ACAD DERMATOL
JUNE 2017