The poster sessions at 34th Annual Fall Clinical Dermatology Conference held in Las Vegas, NV, provided attendees with a record number of posters on skin conditions and management approaches. This article highlights posters presented on psoriasis.
Response to Tofacitinib Asessed in Subgroup Analysis
The efficacy and safety of the tofacitinib (Xeljanz, Pfizer Inc.) 5 mg and 10 mg twice daily has been demonstrated in patients with moderate-to-severe psoriasis in 2 randomized, double-blind, Phase III trials. In a new study, Menter et al pooled data from these 2 trials to report efficacy outcomes in patient subgroups by baseline characteristics.
Patients in both studies were randomized 2:2:1 to the novel oral Janus kinase inhibitor tofacitinib 5 mg or 10 mg twice daily or placebo; after 16 weeks, patients were re-randomized to one of the tofacitinib arms through 52 weeks. The primary efficacy endpoints were Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician’s Global Assessment (PGA) of “clear” or “almost clear” at week 16.
At week 16, patients in tofacitinib 5 mg or 10 mg treatment arms elicited significantly higher PASI 75 response rates versus placebo (43% and 59% vs 9%, respectively; P<0.05). Corresponding PASI 75 rates were assessed in subgroups by age, weight and prior biologic therapy: age <65 (total patients in subgroup, N=1,726; 42%, 59% and 9% with tofacitinib 5 mg and 10 mg and placebo, respectively) or age ≥65 (N=117; 52%, 73% and 5%, respectively); weight <60 kg (N=119; 48%, 49% and 11%, respectively), 60 to <90 kg (N=940; 46%, 64% and 10%, respectively) 90 to <120 kg (N=636; 41%, 56% and 9%, respectively), 120 to <150 kg (N=122; 34%, 53% and 4%, respectively) and ≥150 kg (N=25; 21%, 39% and 0%, respectively); body mass index (BMI) <25 (N=448; 48%, 60% and 10%, respectively), 25 to <30 (N=623; 41%, 62% and 7%, respectively), 30 to <40 (N=631; 43%, 57% and 11%, respectively) and ≥40 (N=140; 37%, 54% and 3%, respectively) and prior biologic therapy (N=484; 30%, 48% and 5%, respectively) or no biologic therapy (N=1,359; 48%, 63% and 10%, respectively). Similar patterns were observed in PGA response responses across multiple subgroups.
“At each dose of tofacitinib, efficacy was consistent across multiple patient subgroups. However, elderly patients appeared to respond better to both doses than the overall population. In contrast, response to the 5 mg dose appeared to be lower in those with higher body weight and prior biologic experience; these patients responded well to 10 mg,” concluded the researchers.”
Psoriasis Flare-Ups Impact Daily Life
Flare-ups can be a painful, but common occurrence for individuals living with psoriasis. However, little is known about the effects of flares on patients’ everyday lives with regard to physical and mental functional capabilities. Using patient-reported questionnaire data, Seina et al compared the outcomes of flare-ups and the physical and mental health of 1,100 psoriasis patients.
For the study, a flare-up was defined as anytime when a psoriasis patient had a worsening of symptoms. Patients who experienced a flare frequency of at least once per month were defined as “more-frequent flare group” and the patients who had flares 6 times per year or less were defined as the “less-frequent flare group.” Patients were analyzed and compared across flare frequency categories on various health assessment scores such as the Dermatology Life Quality Index (DLQI).
Overall, 24% of all patients reported having continuous flare-ups, including 31% of moderate patients (N=368) and 47% of severe patients (N=60); 33% of moderate-to-severe patients (N=428) experienced continuous flare-ups. Patients in the more-frequent flare group compared with the less-frequent flare group reported higher rates of absenteeism (5.2% vs 1.2%, respectively), presenteeism-related impairment (18.2% vs 6.8%, respectively), overall work impairment (20.9% vs 6.7%, respectively) and activity impairment (20.1% vs 7.4%, respectively). Furthermore, the more-frequent flare group had a greater proportion of patients reporting that their skin problems have a “very large/extremely large” effect on their lives on the DLQI when compared with the less-frequent flare group (27.8% vs 8.6%, respectively).
“This study demonstrates how patients with more frequent flares had a higher level of work productivity and activity impairment, more hours of work missed due to psoriasis and worse dermatological quality of life and overall quality of life,” concluded the researchers.
Secukinumab Improves PASI Response and Psoriasis-Related Symptoms
Researchers presented findings from 2 studies on secukinumab (Cosentyx, Novartis Pharmaceuticals Corporation) — an anti-interleukin 17A monoclonal antibody. The biologic therapy was FDA approved in January 2015 for the treatment of moderate-to-severe plaque psoriasis in adults. In the first study, Lebwohl et al assessed treatment using the Psoriasis Symptom Diary (PSD) among patients enrolled in ERASURE and FIXTURE studies. PSD measures both the severity and bothersomeness of psoriasis-related symptoms.
Patients age 18 and older were randomized 1:1:1 in ERASURE to receive secukinumab 300 mg, secukinumab 150 mg or placebo; and 1:1:1:1 in FIXTURE which included etanercept (Enbrel, Amgen Inc.) 50 mg twice weekly. Patients were asked to evaluate their psoriasis symptoms and experiences over the previous 24 hours. Weekly scores were derived as averages of 0 to 10 numerical ratings. The analysis focused on itching, pain and scaling. Among patients on secukinumab, differences in the bothersomeness of psoriasis-related symptoms between patients achieving clinical response (eg, PASI 90 or PASI 75) and those not achieving clinical response (not reaching PASI 75) at week 12 were also examined.
Approximately 40% of patients completed the voluntary PSD. For the pooled analysis, the findings showed secukinumab offered significantly greater relief from psoriasis-related itching, pain and scaling compared with placebo or etanercept (P<0.01). Patients treated with secukinumab (ERASURE N=187, FIXTURE N=266) who achieved PASI 90 clinical response had greater reductions in PSD itching and scaling than those who achieved PASI 75, and both achieved greater relief than those patients who did not achieve clinical response (all P<0.05).
In the second study, Griffiths et al evaluated the effect of prior biologic exposure on responsiveness to secukinumab using a pooled subanalysis from 4 psoriasis clinical trials with respect to PASI 90 and 100 responses at week 12. The trials included were ERASURE, FIXTURE, FEATURE and JUNCTURE, which were randomized, double-blind, placebo-controlled, multicenter, Phase III studies evaluating secukinumab efficacy at week 12. The researchers noted that results for FIXTURE etanercept arm were not reported due to lower patient number.
At week 12, mean PASI 90 response rates in patients without prior exposure to biologics and treated with secukinumab 300 mg or 150 mg were 58.1% and 44.6%, respectively, versus placebo (1.3%). In comparison, week 12 mean PASI 90 response rates were slightly lower in patients with prior exposure to biologics and treated with secukinumab 300 mg or 150 mg versus placebo (50.7% and 29.4% vs 0.7%, respectively). In the subset with prior biologic treatment failure at week 12, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg and placebo were 42.0%, 27.5% and 1.8%, respectively. In the subset with responses to prior biologic treatment, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg versus placebo were 55.2%, 30.8% and 0.0%, respectively. PASI 100 response rates were similar to PASI 90 for all subgroups.
“These data suggest secukinumab significantly improves responses versus placebo in subjects with moderate-to-severe plaque psoriasis regardless of prior exposure to biologic therapy and regardless of response to prior biologic therapy,” said the researchers.
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Cal/BD Aerosol Foam Effective for Psoriasis Vulgaris
Results from PSO-ABLE study found that treatment with the fixed combination calciportriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was more effective than topical suspension in patients with psoriasis vulgaris. The findings suggest that the aerosol foam may provide an improved treatment option in this patient population.
The Phase III, investigator-blind trial randomized 463 patients 4:4:1:1 to once-daily treatment with Cal/BD aerosol foam (N=185), Cal/BD topical suspension (N=188), aerosol foam vehicle (N=47) or suspension vehicle (N=43) for up to 12 weeks. The primary endpoint was the proportion of patients achieving clear/almost clear with at least a 2-step improvement in disease severity from baseline at week 4 for Cal/BD aerosol foam versus week 8 for Cal/BD topical suspension. Secondary endpoints included proportion of patients with at least a reduction in PASI 75 score at week 4 for Cal/BD aerosol foam versus at week 8 for Cal/BD topical suspension.
Paul et al reported that a significantly larger proportion of Cal/BD aerosol foam-treated patients achieved treatment success at week 4 versus Cal/BD topical suspension-treated patients at week 8 (38% vs 23%, respectively; odds ratio [OR], 2.55; 95% confidence interval [CI], 1.46-4.46; P<0.001). PASI 75 was also achieved by significantly more patients using the Cal/BD aerosol foam compared with Cal/BD topical suspension (52% vs 35%, respectively; OR, 2.18; 95% CI, 1.37-3.47; P<0.001).
Overall frequency of adverse events (AEs) was similar between both active treatments, with 42% reported for Cal/BD aerosol foam and 45% for Cal/BD topical suspension; the most common AE was upper respiratory tract infection (3% and 5%, respectively). For both active treatments, 2% withdrew as a result of AEs.
ESTEEM Studies Demonstrate Apremilast’s Efficacy and Safety
Researchers presented the results of 2 studies from ESTEEM trial evaluating the safety and efficacy of the oral phosphodiesterase-4 inhibitor apremilast (Otezla, Celgene Corporation). ESTEEM comprises 2 multicenter, randomized, double-blind, placebo-controlled, Phase III trials of apremilast for moderate-to-severe plaque psoriasis. Apremilast was FDA approved in 2014.
In the first study, researchers evaluated the long-term, 2-year safety from ESTEEM 1 that randomized 844 patients to apremilast 30 mg twice daily (N=562) or placebo (N=282). Safety assessments included a collection of AEs and vital signs at all visits, clinical and laboratory testing every 4 weeks, physical examinations every 4 to 8 weeks and 12-lead electrocardiograms at baseline and at the end of each treatment period.
Papp et al reported that apremilast 30 mg demonstrated an acceptable safety profile and was generally well-tolerated for up to 104 weeks of exposure. Furthermore, no new safety signals for apremilast were identified in the second year of exposure as compared with the first. Most AEs were mild or moderate in severity and did not lead to discontinuation. The most frequently reported AEs during the placebo-controlled 0- to 16-week period and the apremilast-exposure periods (0 to ≤52 weeks and >52 to ≤104 weeks) were diarrhea, upper respiratory tract infection, nausea, nasopharyngitis, tension headache and headache. Nausea and diarrhea were the most common AEs leading to discontinuation during 0 to ≤52 weeks of exposure (1.7% and 1.2%, respectively); few patients discontinued apremilast due to an AE during >52 to ≤104 weeks of exposure.
The incidence rates of major cardiac events, solid tumors, hematological malignancies and serious infections were comparable between the placebo and apremilast 30 mg groups in the placebo-controlled 0- to 16-week period. No increase in these events was noted with longer term exposure to apremilast (between 52 and 104 weeks). Weight decrease was reported as an AE in 1.0% of patients during 0 to ≤52 weeks of exposure and in 0.5% during >52 to ≤104 weeks of exposure; none were serious AEs. The majority of patients receiving apremilast 30 mg maintained their body weight within ±5% of baseline, regardless of duration of exposure (76.1%, 0 to ≤52 weeks; 65.1%, >52 to ≤104 weeks).
In the second study, Korman et al assessed the efficacy of apremilast 30 mg twice daily in specified subpopulations based on baseline demographics, baseline disease characteristics and prior psoriasis therapies, at week 16 in ESTEEM 1 and ESTEEM 2. The study included 1,255 patients (placebo, N=419 and apremilast 30 mg, N=836). Of patients randomized to placebo or apremilast 30 mg at baseline, the mean duration of psoriasis was 18.7 and 19.2 years and mean baseline PASI scores were 19.6 and 18.8, respectively; 155 (37.0%) and 318 (38.0%) patients had been treated previously with conventional systemic therapy, and 124 (29.6%) and 254 (30.4%) patients had received prior biologics.
The primary efficacy endpoint was the proportion of patients who achieved ≥75% reduction from baseline in PASI 75 score at week 16. Efficacy data were assessed for the full analysis set, which included all patients who were randomized according to the study protocol. Secondary endpoints included the proportion of patients who achieved static PGA (sPGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline at week 16.
Apremilast was effective across subgroups regardless of baseline demographics and baseline disease severity or prior psoriasis therapy. In ESTEEM 1, PASI 75, PASI 50 and sPGA responses at week 16 showed a treatment effect in favor of apremilast 30 mg versus placebo (33.1%, 58.7% and 21.7% vs 5.3%, 17.0% and 3.9%, respectively). Patients in ESTEEM 2 also showed improvement with apremilast 30 mg versus placebo in PASI 75, PASI 50 and sPGA at week 16 (28.8%, 55.5% and 20.4% vs 5.8%, 19.7% and 4.4%, respectively). The researchers noted that efficacy was similar regardless of baseline BMI.
The poster sessions at 34th Annual Fall Clinical Dermatology Conference held in Las Vegas, NV, provided attendees with a record number of posters on skin conditions and management approaches. This article highlights posters presented on psoriasis.
Response to Tofacitinib Asessed in Subgroup Analysis
The efficacy and safety of the tofacitinib (Xeljanz, Pfizer Inc.) 5 mg and 10 mg twice daily has been demonstrated in patients with moderate-to-severe psoriasis in 2 randomized, double-blind, Phase III trials. In a new study, Menter et al pooled data from these 2 trials to report efficacy outcomes in patient subgroups by baseline characteristics.
Patients in both studies were randomized 2:2:1 to the novel oral Janus kinase inhibitor tofacitinib 5 mg or 10 mg twice daily or placebo; after 16 weeks, patients were re-randomized to one of the tofacitinib arms through 52 weeks. The primary efficacy endpoints were Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician’s Global Assessment (PGA) of “clear” or “almost clear” at week 16.
At week 16, patients in tofacitinib 5 mg or 10 mg treatment arms elicited significantly higher PASI 75 response rates versus placebo (43% and 59% vs 9%, respectively; P<0.05). Corresponding PASI 75 rates were assessed in subgroups by age, weight and prior biologic therapy: age <65 (total patients in subgroup, N=1,726; 42%, 59% and 9% with tofacitinib 5 mg and 10 mg and placebo, respectively) or age ≥65 (N=117; 52%, 73% and 5%, respectively); weight <60 kg (N=119; 48%, 49% and 11%, respectively), 60 to <90 kg (N=940; 46%, 64% and 10%, respectively) 90 to <120 kg (N=636; 41%, 56% and 9%, respectively), 120 to <150 kg (N=122; 34%, 53% and 4%, respectively) and ≥150 kg (N=25; 21%, 39% and 0%, respectively); body mass index (BMI) <25 (N=448; 48%, 60% and 10%, respectively), 25 to <30 (N=623; 41%, 62% and 7%, respectively), 30 to <40 (N=631; 43%, 57% and 11%, respectively) and ≥40 (N=140; 37%, 54% and 3%, respectively) and prior biologic therapy (N=484; 30%, 48% and 5%, respectively) or no biologic therapy (N=1,359; 48%, 63% and 10%, respectively). Similar patterns were observed in PGA response responses across multiple subgroups.
“At each dose of tofacitinib, efficacy was consistent across multiple patient subgroups. However, elderly patients appeared to respond better to both doses than the overall population. In contrast, response to the 5 mg dose appeared to be lower in those with higher body weight and prior biologic experience; these patients responded well to 10 mg,” concluded the researchers.”
Psoriasis Flare-Ups Impact Daily Life
Flare-ups can be a painful, but common occurrence for individuals living with psoriasis. However, little is known about the effects of flares on patients’ everyday lives with regard to physical and mental functional capabilities. Using patient-reported questionnaire data, Seina et al compared the outcomes of flare-ups and the physical and mental health of 1,100 psoriasis patients.
For the study, a flare-up was defined as anytime when a psoriasis patient had a worsening of symptoms. Patients who experienced a flare frequency of at least once per month were defined as “more-frequent flare group” and the patients who had flares 6 times per year or less were defined as the “less-frequent flare group.” Patients were analyzed and compared across flare frequency categories on various health assessment scores such as the Dermatology Life Quality Index (DLQI).
Overall, 24% of all patients reported having continuous flare-ups, including 31% of moderate patients (N=368) and 47% of severe patients (N=60); 33% of moderate-to-severe patients (N=428) experienced continuous flare-ups. Patients in the more-frequent flare group compared with the less-frequent flare group reported higher rates of absenteeism (5.2% vs 1.2%, respectively), presenteeism-related impairment (18.2% vs 6.8%, respectively), overall work impairment (20.9% vs 6.7%, respectively) and activity impairment (20.1% vs 7.4%, respectively). Furthermore, the more-frequent flare group had a greater proportion of patients reporting that their skin problems have a “very large/extremely large” effect on their lives on the DLQI when compared with the less-frequent flare group (27.8% vs 8.6%, respectively).
“This study demonstrates how patients with more frequent flares had a higher level of work productivity and activity impairment, more hours of work missed due to psoriasis and worse dermatological quality of life and overall quality of life,” concluded the researchers.
Secukinumab Improves PASI Response and Psoriasis-Related Symptoms
Researchers presented findings from 2 studies on secukinumab (Cosentyx, Novartis Pharmaceuticals Corporation) — an anti-interleukin 17A monoclonal antibody. The biologic therapy was FDA approved in January 2015 for the treatment of moderate-to-severe plaque psoriasis in adults. In the first study, Lebwohl et al assessed treatment using the Psoriasis Symptom Diary (PSD) among patients enrolled in ERASURE and FIXTURE studies. PSD measures both the severity and bothersomeness of psoriasis-related symptoms.
Patients age 18 and older were randomized 1:1:1 in ERASURE to receive secukinumab 300 mg, secukinumab 150 mg or placebo; and 1:1:1:1 in FIXTURE which included etanercept (Enbrel, Amgen Inc.) 50 mg twice weekly. Patients were asked to evaluate their psoriasis symptoms and experiences over the previous 24 hours. Weekly scores were derived as averages of 0 to 10 numerical ratings. The analysis focused on itching, pain and scaling. Among patients on secukinumab, differences in the bothersomeness of psoriasis-related symptoms between patients achieving clinical response (eg, PASI 90 or PASI 75) and those not achieving clinical response (not reaching PASI 75) at week 12 were also examined.
Approximately 40% of patients completed the voluntary PSD. For the pooled analysis, the findings showed secukinumab offered significantly greater relief from psoriasis-related itching, pain and scaling compared with placebo or etanercept (P<0.01). Patients treated with secukinumab (ERASURE N=187, FIXTURE N=266) who achieved PASI 90 clinical response had greater reductions in PSD itching and scaling than those who achieved PASI 75, and both achieved greater relief than those patients who did not achieve clinical response (all P<0.05).
In the second study, Griffiths et al evaluated the effect of prior biologic exposure on responsiveness to secukinumab using a pooled subanalysis from 4 psoriasis clinical trials with respect to PASI 90 and 100 responses at week 12. The trials included were ERASURE, FIXTURE, FEATURE and JUNCTURE, which were randomized, double-blind, placebo-controlled, multicenter, Phase III studies evaluating secukinumab efficacy at week 12. The researchers noted that results for FIXTURE etanercept arm were not reported due to lower patient number.
At week 12, mean PASI 90 response rates in patients without prior exposure to biologics and treated with secukinumab 300 mg or 150 mg were 58.1% and 44.6%, respectively, versus placebo (1.3%). In comparison, week 12 mean PASI 90 response rates were slightly lower in patients with prior exposure to biologics and treated with secukinumab 300 mg or 150 mg versus placebo (50.7% and 29.4% vs 0.7%, respectively). In the subset with prior biologic treatment failure at week 12, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg and placebo were 42.0%, 27.5% and 1.8%, respectively. In the subset with responses to prior biologic treatment, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg versus placebo were 55.2%, 30.8% and 0.0%, respectively. PASI 100 response rates were similar to PASI 90 for all subgroups.
“These data suggest secukinumab significantly improves responses versus placebo in subjects with moderate-to-severe plaque psoriasis regardless of prior exposure to biologic therapy and regardless of response to prior biologic therapy,” said the researchers.
Article continues on page 2
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Cal/BD Aerosol Foam Effective for Psoriasis Vulgaris
Results from PSO-ABLE study found that treatment with the fixed combination calciportriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was more effective than topical suspension in patients with psoriasis vulgaris. The findings suggest that the aerosol foam may provide an improved treatment option in this patient population.
The Phase III, investigator-blind trial randomized 463 patients 4:4:1:1 to once-daily treatment with Cal/BD aerosol foam (N=185), Cal/BD topical suspension (N=188), aerosol foam vehicle (N=47) or suspension vehicle (N=43) for up to 12 weeks. The primary endpoint was the proportion of patients achieving clear/almost clear with at least a 2-step improvement in disease severity from baseline at week 4 for Cal/BD aerosol foam versus week 8 for Cal/BD topical suspension. Secondary endpoints included proportion of patients with at least a reduction in PASI 75 score at week 4 for Cal/BD aerosol foam versus at week 8 for Cal/BD topical suspension.
Paul et al reported that a significantly larger proportion of Cal/BD aerosol foam-treated patients achieved treatment success at week 4 versus Cal/BD topical suspension-treated patients at week 8 (38% vs 23%, respectively; odds ratio [OR], 2.55; 95% confidence interval [CI], 1.46-4.46; P<0.001). PASI 75 was also achieved by significantly more patients using the Cal/BD aerosol foam compared with Cal/BD topical suspension (52% vs 35%, respectively; OR, 2.18; 95% CI, 1.37-3.47; P<0.001).
Overall frequency of adverse events (AEs) was similar between both active treatments, with 42% reported for Cal/BD aerosol foam and 45% for Cal/BD topical suspension; the most common AE was upper respiratory tract infection (3% and 5%, respectively). For both active treatments, 2% withdrew as a result of AEs.
ESTEEM Studies Demonstrate Apremilast’s Efficacy and Safety
Researchers presented the results of 2 studies from ESTEEM trial evaluating the safety and efficacy of the oral phosphodiesterase-4 inhibitor apremilast (Otezla, Celgene Corporation). ESTEEM comprises 2 multicenter, randomized, double-blind, placebo-controlled, Phase III trials of apremilast for moderate-to-severe plaque psoriasis. Apremilast was FDA approved in 2014.
In the first study, researchers evaluated the long-term, 2-year safety from ESTEEM 1 that randomized 844 patients to apremilast 30 mg twice daily (N=562) or placebo (N=282). Safety assessments included a collection of AEs and vital signs at all visits, clinical and laboratory testing every 4 weeks, physical examinations every 4 to 8 weeks and 12-lead electrocardiograms at baseline and at the end of each treatment period.
Papp et al reported that apremilast 30 mg demonstrated an acceptable safety profile and was generally well-tolerated for up to 104 weeks of exposure. Furthermore, no new safety signals for apremilast were identified in the second year of exposure as compared with the first. Most AEs were mild or moderate in severity and did not lead to discontinuation. The most frequently reported AEs during the placebo-controlled 0- to 16-week period and the apremilast-exposure periods (0 to ≤52 weeks and >52 to ≤104 weeks) were diarrhea, upper respiratory tract infection, nausea, nasopharyngitis, tension headache and headache. Nausea and diarrhea were the most common AEs leading to discontinuation during 0 to ≤52 weeks of exposure (1.7% and 1.2%, respectively); few patients discontinued apremilast due to an AE during >52 to ≤104 weeks of exposure.
The incidence rates of major cardiac events, solid tumors, hematological malignancies and serious infections were comparable between the placebo and apremilast 30 mg groups in the placebo-controlled 0- to 16-week period. No increase in these events was noted with longer term exposure to apremilast (between 52 and 104 weeks). Weight decrease was reported as an AE in 1.0% of patients during 0 to ≤52 weeks of exposure and in 0.5% during >52 to ≤104 weeks of exposure; none were serious AEs. The majority of patients receiving apremilast 30 mg maintained their body weight within ±5% of baseline, regardless of duration of exposure (76.1%, 0 to ≤52 weeks; 65.1%, >52 to ≤104 weeks).
In the second study, Korman et al assessed the efficacy of apremilast 30 mg twice daily in specified subpopulations based on baseline demographics, baseline disease characteristics and prior psoriasis therapies, at week 16 in ESTEEM 1 and ESTEEM 2. The study included 1,255 patients (placebo, N=419 and apremilast 30 mg, N=836). Of patients randomized to placebo or apremilast 30 mg at baseline, the mean duration of psoriasis was 18.7 and 19.2 years and mean baseline PASI scores were 19.6 and 18.8, respectively; 155 (37.0%) and 318 (38.0%) patients had been treated previously with conventional systemic therapy, and 124 (29.6%) and 254 (30.4%) patients had received prior biologics.
The primary efficacy endpoint was the proportion of patients who achieved ≥75% reduction from baseline in PASI 75 score at week 16. Efficacy data were assessed for the full analysis set, which included all patients who were randomized according to the study protocol. Secondary endpoints included the proportion of patients who achieved static PGA (sPGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline at week 16.
Apremilast was effective across subgroups regardless of baseline demographics and baseline disease severity or prior psoriasis therapy. In ESTEEM 1, PASI 75, PASI 50 and sPGA responses at week 16 showed a treatment effect in favor of apremilast 30 mg versus placebo (33.1%, 58.7% and 21.7% vs 5.3%, 17.0% and 3.9%, respectively). Patients in ESTEEM 2 also showed improvement with apremilast 30 mg versus placebo in PASI 75, PASI 50 and sPGA at week 16 (28.8%, 55.5% and 20.4% vs 5.8%, 19.7% and 4.4%, respectively). The researchers noted that efficacy was similar regardless of baseline BMI.
The poster sessions at 34th Annual Fall Clinical Dermatology Conference held in Las Vegas, NV, provided attendees with a record number of posters on skin conditions and management approaches. This article highlights posters presented on psoriasis.
Response to Tofacitinib Asessed in Subgroup Analysis
The efficacy and safety of the tofacitinib (Xeljanz, Pfizer Inc.) 5 mg and 10 mg twice daily has been demonstrated in patients with moderate-to-severe psoriasis in 2 randomized, double-blind, Phase III trials. In a new study, Menter et al pooled data from these 2 trials to report efficacy outcomes in patient subgroups by baseline characteristics.
Patients in both studies were randomized 2:2:1 to the novel oral Janus kinase inhibitor tofacitinib 5 mg or 10 mg twice daily or placebo; after 16 weeks, patients were re-randomized to one of the tofacitinib arms through 52 weeks. The primary efficacy endpoints were Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician’s Global Assessment (PGA) of “clear” or “almost clear” at week 16.
At week 16, patients in tofacitinib 5 mg or 10 mg treatment arms elicited significantly higher PASI 75 response rates versus placebo (43% and 59% vs 9%, respectively; P<0.05). Corresponding PASI 75 rates were assessed in subgroups by age, weight and prior biologic therapy: age <65 (total patients in subgroup, N=1,726; 42%, 59% and 9% with tofacitinib 5 mg and 10 mg and placebo, respectively) or age ≥65 (N=117; 52%, 73% and 5%, respectively); weight <60 kg (N=119; 48%, 49% and 11%, respectively), 60 to <90 kg (N=940; 46%, 64% and 10%, respectively) 90 to <120 kg (N=636; 41%, 56% and 9%, respectively), 120 to <150 kg (N=122; 34%, 53% and 4%, respectively) and ≥150 kg (N=25; 21%, 39% and 0%, respectively); body mass index (BMI) <25 (N=448; 48%, 60% and 10%, respectively), 25 to <30 (N=623; 41%, 62% and 7%, respectively), 30 to <40 (N=631; 43%, 57% and 11%, respectively) and ≥40 (N=140; 37%, 54% and 3%, respectively) and prior biologic therapy (N=484; 30%, 48% and 5%, respectively) or no biologic therapy (N=1,359; 48%, 63% and 10%, respectively). Similar patterns were observed in PGA response responses across multiple subgroups.
“At each dose of tofacitinib, efficacy was consistent across multiple patient subgroups. However, elderly patients appeared to respond better to both doses than the overall population. In contrast, response to the 5 mg dose appeared to be lower in those with higher body weight and prior biologic experience; these patients responded well to 10 mg,” concluded the researchers.”
Psoriasis Flare-Ups Impact Daily Life
Flare-ups can be a painful, but common occurrence for individuals living with psoriasis. However, little is known about the effects of flares on patients’ everyday lives with regard to physical and mental functional capabilities. Using patient-reported questionnaire data, Seina et al compared the outcomes of flare-ups and the physical and mental health of 1,100 psoriasis patients.
For the study, a flare-up was defined as anytime when a psoriasis patient had a worsening of symptoms. Patients who experienced a flare frequency of at least once per month were defined as “more-frequent flare group” and the patients who had flares 6 times per year or less were defined as the “less-frequent flare group.” Patients were analyzed and compared across flare frequency categories on various health assessment scores such as the Dermatology Life Quality Index (DLQI).
Overall, 24% of all patients reported having continuous flare-ups, including 31% of moderate patients (N=368) and 47% of severe patients (N=60); 33% of moderate-to-severe patients (N=428) experienced continuous flare-ups. Patients in the more-frequent flare group compared with the less-frequent flare group reported higher rates of absenteeism (5.2% vs 1.2%, respectively), presenteeism-related impairment (18.2% vs 6.8%, respectively), overall work impairment (20.9% vs 6.7%, respectively) and activity impairment (20.1% vs 7.4%, respectively). Furthermore, the more-frequent flare group had a greater proportion of patients reporting that their skin problems have a “very large/extremely large” effect on their lives on the DLQI when compared with the less-frequent flare group (27.8% vs 8.6%, respectively).
“This study demonstrates how patients with more frequent flares had a higher level of work productivity and activity impairment, more hours of work missed due to psoriasis and worse dermatological quality of life and overall quality of life,” concluded the researchers.
Secukinumab Improves PASI Response and Psoriasis-Related Symptoms
Researchers presented findings from 2 studies on secukinumab (Cosentyx, Novartis Pharmaceuticals Corporation) — an anti-interleukin 17A monoclonal antibody. The biologic therapy was FDA approved in January 2015 for the treatment of moderate-to-severe plaque psoriasis in adults. In the first study, Lebwohl et al assessed treatment using the Psoriasis Symptom Diary (PSD) among patients enrolled in ERASURE and FIXTURE studies. PSD measures both the severity and bothersomeness of psoriasis-related symptoms.
Patients age 18 and older were randomized 1:1:1 in ERASURE to receive secukinumab 300 mg, secukinumab 150 mg or placebo; and 1:1:1:1 in FIXTURE which included etanercept (Enbrel, Amgen Inc.) 50 mg twice weekly. Patients were asked to evaluate their psoriasis symptoms and experiences over the previous 24 hours. Weekly scores were derived as averages of 0 to 10 numerical ratings. The analysis focused on itching, pain and scaling. Among patients on secukinumab, differences in the bothersomeness of psoriasis-related symptoms between patients achieving clinical response (eg, PASI 90 or PASI 75) and those not achieving clinical response (not reaching PASI 75) at week 12 were also examined.
Approximately 40% of patients completed the voluntary PSD. For the pooled analysis, the findings showed secukinumab offered significantly greater relief from psoriasis-related itching, pain and scaling compared with placebo or etanercept (P<0.01). Patients treated with secukinumab (ERASURE N=187, FIXTURE N=266) who achieved PASI 90 clinical response had greater reductions in PSD itching and scaling than those who achieved PASI 75, and both achieved greater relief than those patients who did not achieve clinical response (all P<0.05).
In the second study, Griffiths et al evaluated the effect of prior biologic exposure on responsiveness to secukinumab using a pooled subanalysis from 4 psoriasis clinical trials with respect to PASI 90 and 100 responses at week 12. The trials included were ERASURE, FIXTURE, FEATURE and JUNCTURE, which were randomized, double-blind, placebo-controlled, multicenter, Phase III studies evaluating secukinumab efficacy at week 12. The researchers noted that results for FIXTURE etanercept arm were not reported due to lower patient number.
At week 12, mean PASI 90 response rates in patients without prior exposure to biologics and treated with secukinumab 300 mg or 150 mg were 58.1% and 44.6%, respectively, versus placebo (1.3%). In comparison, week 12 mean PASI 90 response rates were slightly lower in patients with prior exposure to biologics and treated with secukinumab 300 mg or 150 mg versus placebo (50.7% and 29.4% vs 0.7%, respectively). In the subset with prior biologic treatment failure at week 12, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg and placebo were 42.0%, 27.5% and 1.8%, respectively. In the subset with responses to prior biologic treatment, PASI 90 response rates in patients treated with secukinumab 300 mg or 150 mg versus placebo were 55.2%, 30.8% and 0.0%, respectively. PASI 100 response rates were similar to PASI 90 for all subgroups.
“These data suggest secukinumab significantly improves responses versus placebo in subjects with moderate-to-severe plaque psoriasis regardless of prior exposure to biologic therapy and regardless of response to prior biologic therapy,” said the researchers.
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Cal/BD Aerosol Foam Effective for Psoriasis Vulgaris
Results from PSO-ABLE study found that treatment with the fixed combination calciportriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was more effective than topical suspension in patients with psoriasis vulgaris. The findings suggest that the aerosol foam may provide an improved treatment option in this patient population.
The Phase III, investigator-blind trial randomized 463 patients 4:4:1:1 to once-daily treatment with Cal/BD aerosol foam (N=185), Cal/BD topical suspension (N=188), aerosol foam vehicle (N=47) or suspension vehicle (N=43) for up to 12 weeks. The primary endpoint was the proportion of patients achieving clear/almost clear with at least a 2-step improvement in disease severity from baseline at week 4 for Cal/BD aerosol foam versus week 8 for Cal/BD topical suspension. Secondary endpoints included proportion of patients with at least a reduction in PASI 75 score at week 4 for Cal/BD aerosol foam versus at week 8 for Cal/BD topical suspension.
Paul et al reported that a significantly larger proportion of Cal/BD aerosol foam-treated patients achieved treatment success at week 4 versus Cal/BD topical suspension-treated patients at week 8 (38% vs 23%, respectively; odds ratio [OR], 2.55; 95% confidence interval [CI], 1.46-4.46; P<0.001). PASI 75 was also achieved by significantly more patients using the Cal/BD aerosol foam compared with Cal/BD topical suspension (52% vs 35%, respectively; OR, 2.18; 95% CI, 1.37-3.47; P<0.001).
Overall frequency of adverse events (AEs) was similar between both active treatments, with 42% reported for Cal/BD aerosol foam and 45% for Cal/BD topical suspension; the most common AE was upper respiratory tract infection (3% and 5%, respectively). For both active treatments, 2% withdrew as a result of AEs.
ESTEEM Studies Demonstrate Apremilast’s Efficacy and Safety
Researchers presented the results of 2 studies from ESTEEM trial evaluating the safety and efficacy of the oral phosphodiesterase-4 inhibitor apremilast (Otezla, Celgene Corporation). ESTEEM comprises 2 multicenter, randomized, double-blind, placebo-controlled, Phase III trials of apremilast for moderate-to-severe plaque psoriasis. Apremilast was FDA approved in 2014.
In the first study, researchers evaluated the long-term, 2-year safety from ESTEEM 1 that randomized 844 patients to apremilast 30 mg twice daily (N=562) or placebo (N=282). Safety assessments included a collection of AEs and vital signs at all visits, clinical and laboratory testing every 4 weeks, physical examinations every 4 to 8 weeks and 12-lead electrocardiograms at baseline and at the end of each treatment period.
Papp et al reported that apremilast 30 mg demonstrated an acceptable safety profile and was generally well-tolerated for up to 104 weeks of exposure. Furthermore, no new safety signals for apremilast were identified in the second year of exposure as compared with the first. Most AEs were mild or moderate in severity and did not lead to discontinuation. The most frequently reported AEs during the placebo-controlled 0- to 16-week period and the apremilast-exposure periods (0 to ≤52 weeks and >52 to ≤104 weeks) were diarrhea, upper respiratory tract infection, nausea, nasopharyngitis, tension headache and headache. Nausea and diarrhea were the most common AEs leading to discontinuation during 0 to ≤52 weeks of exposure (1.7% and 1.2%, respectively); few patients discontinued apremilast due to an AE during >52 to ≤104 weeks of exposure.
The incidence rates of major cardiac events, solid tumors, hematological malignancies and serious infections were comparable between the placebo and apremilast 30 mg groups in the placebo-controlled 0- to 16-week period. No increase in these events was noted with longer term exposure to apremilast (between 52 and 104 weeks). Weight decrease was reported as an AE in 1.0% of patients during 0 to ≤52 weeks of exposure and in 0.5% during >52 to ≤104 weeks of exposure; none were serious AEs. The majority of patients receiving apremilast 30 mg maintained their body weight within ±5% of baseline, regardless of duration of exposure (76.1%, 0 to ≤52 weeks; 65.1%, >52 to ≤104 weeks).
In the second study, Korman et al assessed the efficacy of apremilast 30 mg twice daily in specified subpopulations based on baseline demographics, baseline disease characteristics and prior psoriasis therapies, at week 16 in ESTEEM 1 and ESTEEM 2. The study included 1,255 patients (placebo, N=419 and apremilast 30 mg, N=836). Of patients randomized to placebo or apremilast 30 mg at baseline, the mean duration of psoriasis was 18.7 and 19.2 years and mean baseline PASI scores were 19.6 and 18.8, respectively; 155 (37.0%) and 318 (38.0%) patients had been treated previously with conventional systemic therapy, and 124 (29.6%) and 254 (30.4%) patients had received prior biologics.
The primary efficacy endpoint was the proportion of patients who achieved ≥75% reduction from baseline in PASI 75 score at week 16. Efficacy data were assessed for the full analysis set, which included all patients who were randomized according to the study protocol. Secondary endpoints included the proportion of patients who achieved static PGA (sPGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline at week 16.
Apremilast was effective across subgroups regardless of baseline demographics and baseline disease severity or prior psoriasis therapy. In ESTEEM 1, PASI 75, PASI 50 and sPGA responses at week 16 showed a treatment effect in favor of apremilast 30 mg versus placebo (33.1%, 58.7% and 21.7% vs 5.3%, 17.0% and 3.9%, respectively). Patients in ESTEEM 2 also showed improvement with apremilast 30 mg versus placebo in PASI 75, PASI 50 and sPGA at week 16 (28.8%, 55.5% and 20.4% vs 5.8%, 19.7% and 4.4%, respectively). The researchers noted that efficacy was similar regardless of baseline BMI.
