The posters presented at The Winter Clinical Dermatology Conference-Hawaii offered dermatologists the latest research and management approaches for skin conditions they encounter in clinical practice. This article highlights some of the posters presented on psoriasis.
Real-World Data Shows Effectiveness, Patient Satisfaction with Apremilast
In a new study, Armstrong and Levi sought to address the limited real-world data on the use of the oral phosphodiesterase-4 inhibitor apremilast (Otezla) in the dermatology setting. The retrospective, multicenter, longitudinal, observational cohort study evaluated real-world patient characteristics, clinical effectiveness, and prescribing patterns of apremilast in participants with moderate to severe psoriasis using a database of >5000 US dermatology providers.
The study included 7517 participants aged ≥18 years with a psoriasis diagnosis who were receiving apremilast during the study period (October 1, 2014 to January 31, 2016). Clinical effectiveness of apremilast was assessed in patients with ≥2 data points (ie, at time of prescription and ≥1 within 6 months) using the Physician Global Assessment (PGA) and affected body surface area (BSA). Patient-perceived overall treatment effectiveness was evaluated in participants receiving apremilast for ≥90 days. The effect of apremilast on PGA and BSA was evaluated in a subset of participants who met the inclusion criteria.
Apremilast was effective in reducing PGA and BSA in the study cohort. At apremilast initiation, adjusted mean PGA was 2.79 in systemic-naïve participants (n=173) and 2.48 in systemic-experienced participants (n=208). Within 6 months of apremilast treatment, PGA decreased by mean 1.71 and by 1.02 in the systemic-naïve and systemic-experienced cohorts, respectively (P<.001). At apremilast initiation, adjusted mean BSA was 17.85 in systemic-naïve participants (n=196) and 12.93 in systemic-experienced participants (n=177); statistically significant reductions in BSA were observed in both groups after 6 months of treatment, with 62% (P<.01) and 60% (P=.002) reductions in BSA in systemic-naïve and systemic-experienced participants, respectively. Furthermore, 86.2% of participants with ≥1 patient-perceived overall treatment effectiveness assessment agreed apremilast was effective in clearing their skin of psoriasis.
Reference
Armstrong A, Levi E. A retrospective cohort study of real-world experience with apremilast in patients with moderate to severe plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Study Evaluates Long-Term Use of Apremilast
Pooled analysis from ESTEEM 1 and 2 trials demonstrated that apremilast 30 mg has an acceptable safety profile and was well tolerated for ≥156 weeks of exposure, with no new signals or increases in severity or frequency of adverse events (AEs) with long-term treatment.
In the ESTEEM 1 and 2 analysis, the apremilast–exposure period (all individuals who received apremilast, despite when initiated [0 to ≥156 weeks]) included 1184 participants treated with apremilast 30 mg twice a day. During the 0- to ≤52-week apremilast-exposure period, Papp and colleagues reported that AEs occurring in ≥5% of participants were diarrhea, nausea, headache, and tension headache. Most cases of diarrhea and nausea were mild to moderate in severity, occurred during the first week of dosing, and generally resolved within 1 month. Furthermore, based on exposure-adjusted incident rates (EAIR)/100 patient-years, the study showed that AEs, serious AEs, and discontinuation of study drug due to AEs did not increase with long-term exposure compared with 0- to ≤52-week period. For the overall exposure period, EAIR/100 patient-years for serious AEs and for discontinuation due to AEs was 5.9 and 7.0, respectively.
No increases in rates of major adverse cardiac events (EAIR 0.5), malignancies (EAIR 1.2), depression (EAIR 1.8), or suicide attempt (EAIR 0.1) were reported during the 0- to ≥156-week period compared with the 0- to ≤52-week period. The researchers also observed no serious opportunistic infection, reactivation of tuberculosis infection, or clinically meaningful effects on laboratory measurements.
“Pooled safety analyses from the ESTEEM trials were consistent with those from the polled PALACE 1-3 trials over the same apremilast-exposure periods, even in a patient population receiving concomitant disease-modifying antirheumatic drugs,” said researchers.
Reference
Papp KA, Sobell JM, Paris M, Day RM, Chen R, Paul C. Pooled safety and tolerability analyses of apremilast for ≥156 weeks from phase 3 clinical trials. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Article continues on page 2
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Brodalumab Demonstrates Efficacy vs Ustekinumab
Results from the AMAGINE clinical trials showed that brodalumab demonstrated significantly greater response rates compared with ustekinumab (Stelara) for Psoriasis Area Severity Index (PASI) 75 and static Physician Global Assessment (sPGA) over 52 weeks in individuals with moderate to severe plaque psoriasis. Brodalumab is a fully human IL-17A monoclonal antibody.
Papp and colleagues investigated the efficacy of brodalumab in 3 multicenter, randomized, double-blind studies in 4363 participants with moderate to severe plaque psoriasis. In AMGINE-1, participants were randomized 1:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, or placebo during the 12-week induction phase. During the withdrawal and retreatment phase, individuals who had sPGA success at week 12 were randomized 1:1 to placebo or continued brodalumab at the induction dose. In the induction phase of AMAGINE-2 and AMAGINE-3, participants were randomized 2:2:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, ustekinumab, or placebo.
For the maintenance phase, participants originally randomized to either brodalumab treatment arms were randomized again (2:2:2:1) to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, brodalumab 140 mg every 4 weeks, or brodalumab 140 mg every 8 weeks. Individuals taking ustekinumab continued to receive the drug while participants originally randomized to receive placebo began receiving brodalumab 210 mg every 2 weeks for 40 weeks.
For PASI 75 and sPGA (0 [clear] or 1[almost clear]), brodalumab 210 mg every 2 weeks showed significantly greater response rates compared with ustekinumab at week 12 (85.3% and 78.6% vs 69.7% and 59.1%, respectively). At week 52, the researchers observed a significantly greater response rate with brodalumab vs ustekinumab for PASI 100 (51.0% vs 28.1%), and sPGA (64.9% vs 45.3%).
Reference
Papp RA, Lebwohl MG, Green LJ, et al. Maintenance of clinical efficacy in moderate-to-severe plaque psoriasis: a 52-week evaluation of brodalumab in three multicenter, double-blind studies of 4363 subjects. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Sustained Efficacy with Secukinumab Over 4 Years
Individuals with psoriasis treated with secukinumab (Cosentyx), an anti-IL-17A monoclonal antibody, sustained high levels of skin clearance and improvement in quality of life with a favorable safety profile through 4 years, according to SCULPTURE extension study findings.
In SCULPTURE, PASI 75 responders at week 12 were randomized to double-blind maintenance treatment of either secukinumab 300 mg or 150 mg subcutaneously administered as fixed-interval dosing occurring once every 4 weeks or in a retreatment-as-needed regimen. Participants who completed 52 weeks of treatment continued into the extension phase and received the same blinded maintenance treatment regimen and dose up to end of year 3. In year 4, the study was open-label, with home administration of treatment. The participants had a mean baseline PSAI of 23.5 ± 8.8, and a mean BSA of 33.1%.
Bissonnette and colleagues reported that secukinumab 300 mg demonstrated sustained efficacy over 4 years of treatment in participants with moderate to severe psoriasis (baseline: n=168, year 1: n=165, and year 4: n=131). Average PASI improvement was >90%, with approximately two-thirds of patients having clear or almost clear skin at year 1 (68.5%); a response that was maintained to year 4 (66.4%). Almost 100% of PASI 90 and PASI 100 response rates were maintained from year 1 to year 4 (43.8% and 43.5%, respectively). PASI ≤1/≤2/≤3 responses at year 1 were 58.6%, 67.9%, and 74.1%, respectively, and were 58.8%, 71%, and 77.1%, respectively, at Year 4. Furthermore, participants experienced long-lasting relief from the burden of psoriasis of 4 years based on the Dermatology Quality Life Index (year 1: 72.7% and year 4: 70.8%). No increase in AEs year-on-year and no new or unexpected safety signals were observed.
Reference
Bissonnette R, Luger T, Thaçi D, et al. Secukinumab demonstrates sustained high efficacy and a favorable safety profile in moderate to severe psoriasis patients through 4 years of treatment (extension of the SCULPTURE study). Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
HP/TAZ Fixed Combination Reduces Psoriasis Signs
The fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion was significantly more effective in achieving treatment success and in reducing psoriasis signs than individual therapy or the vehicle, according to a new study.
The multicenter, randomized, double-blind, vehicle-controlled, phase 2 study included 212 participants with moderate or severe plaque psoriasis. The study’s aim was to investigate the efficacy and safety of once-daily application of HP/TAZ compared with its monads and vehicle. Participants were randomized 2:2:2:1 to HP/TAZ, individual monads, or vehicle once daily for 8 weeks. Efficacy assessments included disease severity (treatment success defined as at least a 2-grade improvement from baseline in the Investigator’s Global Assessment [IGA] score and a score of clear or almost clear), and impact on individual signs of psoriasis at the target lesion (treatment success defined as at least a 2-grade improvement from baseline). Participants had a baseline IGA of 3 (88.9%-96.8%) or 4 (3.2%-11.2%). The majority of participants had baseline severity score of 3 for each psoriasis sign (erythema, plaque elevation, and scaling) at target lesion site. Safety and treatment emergent AEs was evaluated throughout the study.
Researchers reported that 52.5% of participants in the HP/TAZ arm had treatment success compared with 33.3% in the HP group, 18.6% in the TAZ group, and 9.7% in the vehicle group at week 8. Treatment success was also achieved in the HP/TAZ group by 54.2% of patients for erythema, 67.8% for plaque elevation, and 64.4% for scaling and was significantly greater compared with the vehicle or TAZ cohorts. The safety data was consistent with the known safety profile of HP and TAZ, and did not indicate any new safety concerns with the combination medicine. The most frequently reported treatment emergent AEs were application site reactions.
Reference
Stein Gold L, Pariser DM, Sugarman JL, Pillai RS. A phase 2, multicenter, double-blind, randomized, vehicle controlled clinical study to assess the safety and efficacy of a halobetasol/tazarotene fixed combination in the treatment of plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
The posters presented at The Winter Clinical Dermatology Conference-Hawaii offered dermatologists the latest research and management approaches for skin conditions they encounter in clinical practice. This article highlights some of the posters presented on psoriasis.
Real-World Data Shows Effectiveness, Patient Satisfaction with Apremilast
In a new study, Armstrong and Levi sought to address the limited real-world data on the use of the oral phosphodiesterase-4 inhibitor apremilast (Otezla) in the dermatology setting. The retrospective, multicenter, longitudinal, observational cohort study evaluated real-world patient characteristics, clinical effectiveness, and prescribing patterns of apremilast in participants with moderate to severe psoriasis using a database of >5000 US dermatology providers.
The study included 7517 participants aged ≥18 years with a psoriasis diagnosis who were receiving apremilast during the study period (October 1, 2014 to January 31, 2016). Clinical effectiveness of apremilast was assessed in patients with ≥2 data points (ie, at time of prescription and ≥1 within 6 months) using the Physician Global Assessment (PGA) and affected body surface area (BSA). Patient-perceived overall treatment effectiveness was evaluated in participants receiving apremilast for ≥90 days. The effect of apremilast on PGA and BSA was evaluated in a subset of participants who met the inclusion criteria.
Apremilast was effective in reducing PGA and BSA in the study cohort. At apremilast initiation, adjusted mean PGA was 2.79 in systemic-naïve participants (n=173) and 2.48 in systemic-experienced participants (n=208). Within 6 months of apremilast treatment, PGA decreased by mean 1.71 and by 1.02 in the systemic-naïve and systemic-experienced cohorts, respectively (P<.001). At apremilast initiation, adjusted mean BSA was 17.85 in systemic-naïve participants (n=196) and 12.93 in systemic-experienced participants (n=177); statistically significant reductions in BSA were observed in both groups after 6 months of treatment, with 62% (P<.01) and 60% (P=.002) reductions in BSA in systemic-naïve and systemic-experienced participants, respectively. Furthermore, 86.2% of participants with ≥1 patient-perceived overall treatment effectiveness assessment agreed apremilast was effective in clearing their skin of psoriasis.
Reference
Armstrong A, Levi E. A retrospective cohort study of real-world experience with apremilast in patients with moderate to severe plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Study Evaluates Long-Term Use of Apremilast
Pooled analysis from ESTEEM 1 and 2 trials demonstrated that apremilast 30 mg has an acceptable safety profile and was well tolerated for ≥156 weeks of exposure, with no new signals or increases in severity or frequency of adverse events (AEs) with long-term treatment.
In the ESTEEM 1 and 2 analysis, the apremilast–exposure period (all individuals who received apremilast, despite when initiated [0 to ≥156 weeks]) included 1184 participants treated with apremilast 30 mg twice a day. During the 0- to ≤52-week apremilast-exposure period, Papp and colleagues reported that AEs occurring in ≥5% of participants were diarrhea, nausea, headache, and tension headache. Most cases of diarrhea and nausea were mild to moderate in severity, occurred during the first week of dosing, and generally resolved within 1 month. Furthermore, based on exposure-adjusted incident rates (EAIR)/100 patient-years, the study showed that AEs, serious AEs, and discontinuation of study drug due to AEs did not increase with long-term exposure compared with 0- to ≤52-week period. For the overall exposure period, EAIR/100 patient-years for serious AEs and for discontinuation due to AEs was 5.9 and 7.0, respectively.
No increases in rates of major adverse cardiac events (EAIR 0.5), malignancies (EAIR 1.2), depression (EAIR 1.8), or suicide attempt (EAIR 0.1) were reported during the 0- to ≥156-week period compared with the 0- to ≤52-week period. The researchers also observed no serious opportunistic infection, reactivation of tuberculosis infection, or clinically meaningful effects on laboratory measurements.
“Pooled safety analyses from the ESTEEM trials were consistent with those from the polled PALACE 1-3 trials over the same apremilast-exposure periods, even in a patient population receiving concomitant disease-modifying antirheumatic drugs,” said researchers.
Reference
Papp KA, Sobell JM, Paris M, Day RM, Chen R, Paul C. Pooled safety and tolerability analyses of apremilast for ≥156 weeks from phase 3 clinical trials. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Article continues on page 2
{{pagebreak}}
Brodalumab Demonstrates Efficacy vs Ustekinumab
Results from the AMAGINE clinical trials showed that brodalumab demonstrated significantly greater response rates compared with ustekinumab (Stelara) for Psoriasis Area Severity Index (PASI) 75 and static Physician Global Assessment (sPGA) over 52 weeks in individuals with moderate to severe plaque psoriasis. Brodalumab is a fully human IL-17A monoclonal antibody.
Papp and colleagues investigated the efficacy of brodalumab in 3 multicenter, randomized, double-blind studies in 4363 participants with moderate to severe plaque psoriasis. In AMGINE-1, participants were randomized 1:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, or placebo during the 12-week induction phase. During the withdrawal and retreatment phase, individuals who had sPGA success at week 12 were randomized 1:1 to placebo or continued brodalumab at the induction dose. In the induction phase of AMAGINE-2 and AMAGINE-3, participants were randomized 2:2:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, ustekinumab, or placebo.
For the maintenance phase, participants originally randomized to either brodalumab treatment arms were randomized again (2:2:2:1) to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, brodalumab 140 mg every 4 weeks, or brodalumab 140 mg every 8 weeks. Individuals taking ustekinumab continued to receive the drug while participants originally randomized to receive placebo began receiving brodalumab 210 mg every 2 weeks for 40 weeks.
For PASI 75 and sPGA (0 [clear] or 1[almost clear]), brodalumab 210 mg every 2 weeks showed significantly greater response rates compared with ustekinumab at week 12 (85.3% and 78.6% vs 69.7% and 59.1%, respectively). At week 52, the researchers observed a significantly greater response rate with brodalumab vs ustekinumab for PASI 100 (51.0% vs 28.1%), and sPGA (64.9% vs 45.3%).
Reference
Papp RA, Lebwohl MG, Green LJ, et al. Maintenance of clinical efficacy in moderate-to-severe plaque psoriasis: a 52-week evaluation of brodalumab in three multicenter, double-blind studies of 4363 subjects. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Sustained Efficacy with Secukinumab Over 4 Years
Individuals with psoriasis treated with secukinumab (Cosentyx), an anti-IL-17A monoclonal antibody, sustained high levels of skin clearance and improvement in quality of life with a favorable safety profile through 4 years, according to SCULPTURE extension study findings.
In SCULPTURE, PASI 75 responders at week 12 were randomized to double-blind maintenance treatment of either secukinumab 300 mg or 150 mg subcutaneously administered as fixed-interval dosing occurring once every 4 weeks or in a retreatment-as-needed regimen. Participants who completed 52 weeks of treatment continued into the extension phase and received the same blinded maintenance treatment regimen and dose up to end of year 3. In year 4, the study was open-label, with home administration of treatment. The participants had a mean baseline PSAI of 23.5 ± 8.8, and a mean BSA of 33.1%.
Bissonnette and colleagues reported that secukinumab 300 mg demonstrated sustained efficacy over 4 years of treatment in participants with moderate to severe psoriasis (baseline: n=168, year 1: n=165, and year 4: n=131). Average PASI improvement was >90%, with approximately two-thirds of patients having clear or almost clear skin at year 1 (68.5%); a response that was maintained to year 4 (66.4%). Almost 100% of PASI 90 and PASI 100 response rates were maintained from year 1 to year 4 (43.8% and 43.5%, respectively). PASI ≤1/≤2/≤3 responses at year 1 were 58.6%, 67.9%, and 74.1%, respectively, and were 58.8%, 71%, and 77.1%, respectively, at Year 4. Furthermore, participants experienced long-lasting relief from the burden of psoriasis of 4 years based on the Dermatology Quality Life Index (year 1: 72.7% and year 4: 70.8%). No increase in AEs year-on-year and no new or unexpected safety signals were observed.
Reference
Bissonnette R, Luger T, Thaçi D, et al. Secukinumab demonstrates sustained high efficacy and a favorable safety profile in moderate to severe psoriasis patients through 4 years of treatment (extension of the SCULPTURE study). Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
HP/TAZ Fixed Combination Reduces Psoriasis Signs
The fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion was significantly more effective in achieving treatment success and in reducing psoriasis signs than individual therapy or the vehicle, according to a new study.
The multicenter, randomized, double-blind, vehicle-controlled, phase 2 study included 212 participants with moderate or severe plaque psoriasis. The study’s aim was to investigate the efficacy and safety of once-daily application of HP/TAZ compared with its monads and vehicle. Participants were randomized 2:2:2:1 to HP/TAZ, individual monads, or vehicle once daily for 8 weeks. Efficacy assessments included disease severity (treatment success defined as at least a 2-grade improvement from baseline in the Investigator’s Global Assessment [IGA] score and a score of clear or almost clear), and impact on individual signs of psoriasis at the target lesion (treatment success defined as at least a 2-grade improvement from baseline). Participants had a baseline IGA of 3 (88.9%-96.8%) or 4 (3.2%-11.2%). The majority of participants had baseline severity score of 3 for each psoriasis sign (erythema, plaque elevation, and scaling) at target lesion site. Safety and treatment emergent AEs was evaluated throughout the study.
Researchers reported that 52.5% of participants in the HP/TAZ arm had treatment success compared with 33.3% in the HP group, 18.6% in the TAZ group, and 9.7% in the vehicle group at week 8. Treatment success was also achieved in the HP/TAZ group by 54.2% of patients for erythema, 67.8% for plaque elevation, and 64.4% for scaling and was significantly greater compared with the vehicle or TAZ cohorts. The safety data was consistent with the known safety profile of HP and TAZ, and did not indicate any new safety concerns with the combination medicine. The most frequently reported treatment emergent AEs were application site reactions.
Reference
Stein Gold L, Pariser DM, Sugarman JL, Pillai RS. A phase 2, multicenter, double-blind, randomized, vehicle controlled clinical study to assess the safety and efficacy of a halobetasol/tazarotene fixed combination in the treatment of plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
The posters presented at The Winter Clinical Dermatology Conference-Hawaii offered dermatologists the latest research and management approaches for skin conditions they encounter in clinical practice. This article highlights some of the posters presented on psoriasis.
Real-World Data Shows Effectiveness, Patient Satisfaction with Apremilast
In a new study, Armstrong and Levi sought to address the limited real-world data on the use of the oral phosphodiesterase-4 inhibitor apremilast (Otezla) in the dermatology setting. The retrospective, multicenter, longitudinal, observational cohort study evaluated real-world patient characteristics, clinical effectiveness, and prescribing patterns of apremilast in participants with moderate to severe psoriasis using a database of >5000 US dermatology providers.
The study included 7517 participants aged ≥18 years with a psoriasis diagnosis who were receiving apremilast during the study period (October 1, 2014 to January 31, 2016). Clinical effectiveness of apremilast was assessed in patients with ≥2 data points (ie, at time of prescription and ≥1 within 6 months) using the Physician Global Assessment (PGA) and affected body surface area (BSA). Patient-perceived overall treatment effectiveness was evaluated in participants receiving apremilast for ≥90 days. The effect of apremilast on PGA and BSA was evaluated in a subset of participants who met the inclusion criteria.
Apremilast was effective in reducing PGA and BSA in the study cohort. At apremilast initiation, adjusted mean PGA was 2.79 in systemic-naïve participants (n=173) and 2.48 in systemic-experienced participants (n=208). Within 6 months of apremilast treatment, PGA decreased by mean 1.71 and by 1.02 in the systemic-naïve and systemic-experienced cohorts, respectively (P<.001). At apremilast initiation, adjusted mean BSA was 17.85 in systemic-naïve participants (n=196) and 12.93 in systemic-experienced participants (n=177); statistically significant reductions in BSA were observed in both groups after 6 months of treatment, with 62% (P<.01) and 60% (P=.002) reductions in BSA in systemic-naïve and systemic-experienced participants, respectively. Furthermore, 86.2% of participants with ≥1 patient-perceived overall treatment effectiveness assessment agreed apremilast was effective in clearing their skin of psoriasis.
Reference
Armstrong A, Levi E. A retrospective cohort study of real-world experience with apremilast in patients with moderate to severe plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Study Evaluates Long-Term Use of Apremilast
Pooled analysis from ESTEEM 1 and 2 trials demonstrated that apremilast 30 mg has an acceptable safety profile and was well tolerated for ≥156 weeks of exposure, with no new signals or increases in severity or frequency of adverse events (AEs) with long-term treatment.
In the ESTEEM 1 and 2 analysis, the apremilast–exposure period (all individuals who received apremilast, despite when initiated [0 to ≥156 weeks]) included 1184 participants treated with apremilast 30 mg twice a day. During the 0- to ≤52-week apremilast-exposure period, Papp and colleagues reported that AEs occurring in ≥5% of participants were diarrhea, nausea, headache, and tension headache. Most cases of diarrhea and nausea were mild to moderate in severity, occurred during the first week of dosing, and generally resolved within 1 month. Furthermore, based on exposure-adjusted incident rates (EAIR)/100 patient-years, the study showed that AEs, serious AEs, and discontinuation of study drug due to AEs did not increase with long-term exposure compared with 0- to ≤52-week period. For the overall exposure period, EAIR/100 patient-years for serious AEs and for discontinuation due to AEs was 5.9 and 7.0, respectively.
No increases in rates of major adverse cardiac events (EAIR 0.5), malignancies (EAIR 1.2), depression (EAIR 1.8), or suicide attempt (EAIR 0.1) were reported during the 0- to ≥156-week period compared with the 0- to ≤52-week period. The researchers also observed no serious opportunistic infection, reactivation of tuberculosis infection, or clinically meaningful effects on laboratory measurements.
“Pooled safety analyses from the ESTEEM trials were consistent with those from the polled PALACE 1-3 trials over the same apremilast-exposure periods, even in a patient population receiving concomitant disease-modifying antirheumatic drugs,” said researchers.
Reference
Papp KA, Sobell JM, Paris M, Day RM, Chen R, Paul C. Pooled safety and tolerability analyses of apremilast for ≥156 weeks from phase 3 clinical trials. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Article continues on page 2
{{pagebreak}}
Brodalumab Demonstrates Efficacy vs Ustekinumab
Results from the AMAGINE clinical trials showed that brodalumab demonstrated significantly greater response rates compared with ustekinumab (Stelara) for Psoriasis Area Severity Index (PASI) 75 and static Physician Global Assessment (sPGA) over 52 weeks in individuals with moderate to severe plaque psoriasis. Brodalumab is a fully human IL-17A monoclonal antibody.
Papp and colleagues investigated the efficacy of brodalumab in 3 multicenter, randomized, double-blind studies in 4363 participants with moderate to severe plaque psoriasis. In AMGINE-1, participants were randomized 1:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, or placebo during the 12-week induction phase. During the withdrawal and retreatment phase, individuals who had sPGA success at week 12 were randomized 1:1 to placebo or continued brodalumab at the induction dose. In the induction phase of AMAGINE-2 and AMAGINE-3, participants were randomized 2:2:1:1 to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, ustekinumab, or placebo.
For the maintenance phase, participants originally randomized to either brodalumab treatment arms were randomized again (2:2:2:1) to brodalumab 210 mg every 2 weeks, brodalumab 140 mg every 2 weeks, brodalumab 140 mg every 4 weeks, or brodalumab 140 mg every 8 weeks. Individuals taking ustekinumab continued to receive the drug while participants originally randomized to receive placebo began receiving brodalumab 210 mg every 2 weeks for 40 weeks.
For PASI 75 and sPGA (0 [clear] or 1[almost clear]), brodalumab 210 mg every 2 weeks showed significantly greater response rates compared with ustekinumab at week 12 (85.3% and 78.6% vs 69.7% and 59.1%, respectively). At week 52, the researchers observed a significantly greater response rate with brodalumab vs ustekinumab for PASI 100 (51.0% vs 28.1%), and sPGA (64.9% vs 45.3%).
Reference
Papp RA, Lebwohl MG, Green LJ, et al. Maintenance of clinical efficacy in moderate-to-severe plaque psoriasis: a 52-week evaluation of brodalumab in three multicenter, double-blind studies of 4363 subjects. Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
Sustained Efficacy with Secukinumab Over 4 Years
Individuals with psoriasis treated with secukinumab (Cosentyx), an anti-IL-17A monoclonal antibody, sustained high levels of skin clearance and improvement in quality of life with a favorable safety profile through 4 years, according to SCULPTURE extension study findings.
In SCULPTURE, PASI 75 responders at week 12 were randomized to double-blind maintenance treatment of either secukinumab 300 mg or 150 mg subcutaneously administered as fixed-interval dosing occurring once every 4 weeks or in a retreatment-as-needed regimen. Participants who completed 52 weeks of treatment continued into the extension phase and received the same blinded maintenance treatment regimen and dose up to end of year 3. In year 4, the study was open-label, with home administration of treatment. The participants had a mean baseline PSAI of 23.5 ± 8.8, and a mean BSA of 33.1%.
Bissonnette and colleagues reported that secukinumab 300 mg demonstrated sustained efficacy over 4 years of treatment in participants with moderate to severe psoriasis (baseline: n=168, year 1: n=165, and year 4: n=131). Average PASI improvement was >90%, with approximately two-thirds of patients having clear or almost clear skin at year 1 (68.5%); a response that was maintained to year 4 (66.4%). Almost 100% of PASI 90 and PASI 100 response rates were maintained from year 1 to year 4 (43.8% and 43.5%, respectively). PASI ≤1/≤2/≤3 responses at year 1 were 58.6%, 67.9%, and 74.1%, respectively, and were 58.8%, 71%, and 77.1%, respectively, at Year 4. Furthermore, participants experienced long-lasting relief from the burden of psoriasis of 4 years based on the Dermatology Quality Life Index (year 1: 72.7% and year 4: 70.8%). No increase in AEs year-on-year and no new or unexpected safety signals were observed.
Reference
Bissonnette R, Luger T, Thaçi D, et al. Secukinumab demonstrates sustained high efficacy and a favorable safety profile in moderate to severe psoriasis patients through 4 years of treatment (extension of the SCULPTURE study). Poster presented at: 2017 Winter Clinical Dermatology Conference-Hawaii; January 13-18, 2017; Kohala Coast, HI.
HP/TAZ Fixed Combination Reduces Psoriasis Signs
The fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion was significantly more effective in achieving treatment success and in reducing psoriasis signs than individual therapy or the vehicle, according to a new study.
The multicenter, randomized, double-blind, vehicle-controlled, phase 2 study included 212 participants with moderate or severe plaque psoriasis. The study’s aim was to investigate the efficacy and safety of once-daily application of HP/TAZ compared with its monads and vehicle. Participants were randomized 2:2:2:1 to HP/TAZ, individual monads, or vehicle once daily for 8 weeks. Efficacy assessments included disease severity (treatment success defined as at least a 2-grade improvement from baseline in the Investigator’s Global Assessment [IGA] score and a score of clear or almost clear), and impact on individual signs of psoriasis at the target lesion (treatment success defined as at least a 2-grade improvement from baseline). Participants had a baseline IGA of 3 (88.9%-96.8%) or 4 (3.2%-11.2%). The majority of participants had baseline severity score of 3 for each psoriasis sign (erythema, plaque elevation, and scaling) at target lesion site. Safety and treatment emergent AEs was evaluated throughout the study.
Researchers reported that 52.5% of participants in the HP/TAZ arm had treatment success compared with 33.3% in the HP group, 18.6% in the TAZ group, and 9.7% in the vehicle group at week 8. Treatment success was also achieved in the HP/TAZ group by 54.2% of patients for erythema, 67.8% for plaque elevation, and 64.4% for scaling and was significantly greater compared with the vehicle or TAZ cohorts. The safety data was consistent with the known safety profile of HP and TAZ, and did not indicate any new safety concerns with the combination medicine. The most frequently reported treatment emergent AEs were application site reactions.
Reference
Stein Gold L, Pariser DM, Sugarman JL, Pillai RS. A phase 2, multicenter, double-blind, randomized, vehicle controlled clinical study to assess the safety and efficacy of a halobetasol/tazarotene fixed combination in the treatment of plaque psoriasis. Poster presented at: 2017 Winter Clinical Dermatology Conferences-Hawaii; January 13-18, 2017; Kohala Coast, HI.
