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Serious infection events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) Study: Current status of observations
P7969
P8159
Secukinumab versus placebo or etanercept on time to response on patient-reported psoriasis symptoms of pain, itching, and scaling (FIXTURE study) Boni Elewski, MD, University of Alabama, Birmingham, AL, United States; Lori McLeod, PhD, RTI Health Solutions, Research Triangle Park, NJ, United States; Mark Lebwohl, MD, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Usha G. Mallya, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
Serious infection events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) Study: Current status of observations Robert Kalb, MD, SUNY at Buffalo, School of Medicine and Biological Sciences, Buffalo, NY, United States; Craig Leonardi, MD, Central Dermatology, St. Louis, MO, United States; Mark Chevrier, MD, PhD, Janssen Services, LLC., Horsham, PA, United States; Mark Lebwohl, MD, Mount Sinai Medical Center, New York, NY, United States Objective: To report the accrual of serious infections in the PSOLAR study.
Background: Secukinumab (AIN457), a fully human antieinterleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at weeks 12 (vs. placebo and etanercept) and 52 (vs. etanercept) for efficacy and safety in subjects with moderate to severe plaque psoriasis. Psoriasis patients frequently report pain, itching, and scaling. Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD) through week 12, which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment. Methods: FIXTURE (NCT01358578) was a randomized, double-blind, active-comparatore and placebo-controlled, multicenter phase 3 study conducted from Jun 2011 to Jun 2013. It consisted of 3 periods: screening (1-4 weeks), induction (12 weeks), and maintenance (40 weeks). Subjects were randomized 1:1:1:1 to 1 of 4 subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, placebo, or etanercept 50 mg. Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. Each item was completed daily using a 0 to 10 numeric rating scale via an e-diary that allowed completion only from 4 PM to 11:45 PM. Focusing on psoriasis-related pain, itching, and scaling, weekly averages were derived for each item, with higher scores indicating greater severity. Time to response was defined as the period from the randomization date to the response date when a prespecified point improvement from baseline had occurred (2.2 points for itching, 2.2 points for pain, and 2.3 points for scaling). Median time to response and percentage of subjects identified as responders for itching, pain, and scaling were estimated using KaplaneMeier methods by treatment group along with a log-rank test, stratified by geographic region and body weight. Hazard ratios were computed using a stratified Cox proportional hazards regression model.
Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of serious infections in PSOLAR overall and by exposure subgroups is reported. Serious infection rates are assessed using definitions of exposure based on treatment at any time or treatment within 91 days preceding the reported event. In cases of exposure to multiple therapies, serious infection events are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled (22,918 cumulative patient-years of follow-up). Unadjusted rates of serious infection, based on exposure within 91 days preceding the event were: ustekinumab 0.89 events per 100 patient years of observation (PYO) [95% CI, 0.59-1.28; 28/3154 PYO], infliximab/golimumab (almost all infliximab) 2.86 per 100PYO [ 95% CI, 2.143.74; 53/1855 PYO], other biologics (almost all etanercept/adalimumab) 1.71 per 100PYO [95% CI, 1.43-2.04; 131/7639 PYO], nonbiologics 1.16 per 100 PYO [95% CI, 0.96-1.39; 119/10271 PYO], and overall 1.44 [95% CI, 1.29-1.61; 331/22918]. Similar rates of serious infection were observed in the analysis of exposure based on treatment received at any time. Limitations: Because of channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments.
Results: PSD data are available for 530 subjects with baseline and at least 1 week postbaseline. Results are expected by Oct 2013 and will be provided in the final presentation.
Conclusions: Unadjusted rates of serious infection show a trend toward lower rates in the ustekinumab group, despite the rules of event attribution, compared to other biologic groups and similar rates to the no biologic group; higher rates were observed in the infliximab/golimumab group. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR represents a powerful resource for tracking safety events of interest, among patients eligible to receive systemic therapies.
Conclusion: Understanding differences in time to relief of these key symptoms for secukinumab, placebo, and etanercept may guide treatment decisions.
Sponsored 100% by Janssen Research & Development, LLC.
Sponsored 100% by Novartis.
P7938 Secukinumab’s time to psoriasis response on patient-reported psoriasis symptoms (ERASURE study) Alice Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; Ari Gnanasakthy, MBA, MS, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; Bruce Strober, MD, University of Connecticut Health Center, Farmington, NJ, United States; Jessica Jie Zhang, MPH, MS, RTI Health Solutions, Research Triangle Park, NC, United States; Mary Helen Tran, PharmD, MBA, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: Secukinumab (AIN457), a fully human antieinterleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at week 12 (vs. placebo) for efficacy and safety in subjects with moderate to severe plaque psoriasis. Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD), which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment. Methods: ERASURE (NCT01365455) was a randomized, double-blind, placebocontrolled, multicenter phase 3 study conducted from Jan 2011 to Feb 2013. It consisted of 4 periods: screening (1-4 weeks), induction (12 weeks), maintenance (40 weeks), and follow-up (8 weeks). Subjects aged ¼ 18 years were randomized 1:1:1 to 1 of 3 subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, or placebo. Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. Each item was completed daily using a 0 to 10 numeric rating scale via an electronic-diary that allowed completion only from 4 PM to 11:45 PM. Weekly averages were derived for each item, with higher scores indicating greater severity. Time to response was defined as the period from the randomization date (first dose) to the response date when a prespecified point improvement from baseline had occurred (2.2 points for itching, 2.2 points for pain, and 2.3 points for scaling). For each item, the CochranMantel-Haenszel test was used to test the statistical hypotheses that there is no difference in the proportion of subjects with a PSD response in any of the secukinumab groups versus placebo separately by week through week 12. Median time to response and percentage of subjects identified as responders for itching, pain, and scaling were estimated using KaplaneMeier methods by treatment group along with a log-rank test, stratified by geographic region and body weight. Hazard ratios were computed using a stratified Cox proportional hazards regression model.
P8331 Short- and long-term treatment of erythrodermic psoriasis with ustekinumab: A national and multicenter case series Marıa Jose Concha-Garz on, MD, Hospital Universitario de la Princesa, Madrid, Spain; Almudena Godoy-Trapero, MD, Hospital Universitario de la Princesa, Madrid, Spain; Esteban Dauden, PhD, Hospital Universitario de la Princesa, Madrid, Spain; J Garcıa, PhD, Hospital General de Valencia, Valencia, Spain; Jose Luis L opez-Estebaranz, PhD, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain; Ofelia Baniandres, PhD, Hospital Universitario Gregorio Mara~ non, Madrid, Spain; Vicente Rocamora, PhD, Hospital de Manacor, Manacor, Spain Introduction: Erythrodermic psoriasis (EP) is a severe form of psoriasis. There is a number of treatment options, but overall there are few evidence-based data because EP is almost always an exclusionary criterion in clinical trials. Ustekinumab (UTK) is a human monoclonal antibody against interleukin-12 and -23 that has been shown as being effective in the treatment of moderate to severe plaque psoriasis. However, data on the use of UTK in EP are limited. The objective of the study is to determine the efficacy and safety of UTK in patients with EP.
Results: PSD data are available for 299 patients; 285 completed at least 1 week postbaseline. Results are expected by Oct 2013 and will be provided in the final presentation. Conclusion: Understanding the patient perspective associated with time to relief of key psoriasis-related symptoms for secukinumab may guide treatment decisions.
Methods: A national, multicentre, retrospective study was performed. Inclusion criteria: (1) patients with erythrodermic psoriasis, defined as involvement of at least 90% of the body surface area (BSA), and (2) patients with at least 12 weeks of followup after initiation treatment with ustekinumab. UTK dosing and schedules were according to the label and guidelines for psoriasis treatments: 45 mg (11 patients) or 90 mg (1 patient) subcutaneously at weeks 0, 4 and then every 12 weeks. Results: Twelve white patients were included (10 males and 2 females; mean age 54.6 years, range 28-79). All patients had received previous systemic therapies including phototherapy (8), acitretin (6), methotrexate (5), cyclosporine (5), infliximab (6), adalimumab (3), etanercept (2), and efalizumab (1). Four patients were naive to biologic treatment. The mean baseline (range) psoriasis area skin index (PASI) and BSA scores were 46 (23-64) and 90.4 (90-95) respectively. At 16 weeks, PASI 50, PASI 75, PASI 90 and PASI 100 were achieved in 11 (92%), 9 (75%), 8 (67%), and 5 (42%) of the 12 patients, respectively. At 48 weeks, PASI 50, PASI 75, PASI 90, and PASI 100 were achieved in 9 (100%), 7 (78%), 5 (55%), and 2 (22%), respectively, of the 9 patients that were evaluated at that time (2 patients did not reach 48 weeks of follow-up, and 1 patient discontinued the therapy because of a loss of efficacy). Three patients needed a shortening in the interval of administration (8-10 weeks) to be effective enough. No severe side effects were observed. Conclusions: Ustekinumab is safe and effective in the short- and long-term treatment of erythrodermic psoriasis, representing a therapeutic alternative for this severe form of the disease.
Sponsored 100% by Novartis.
Commercial support: None identified.
MAY 2014
J AM ACAD DERMATOL
AB189
P8159
Secukinumab versus placebo or etanercept on time to response on patient-reported psoriasis symptoms of pain, itching, and scaling (FIXTURE study) Boni Elewski, MD, University of Alabama, Birmingham, AL, United States; Lori McLeod, PhD, RTI Health Solutions, Research Triangle Park, NJ, United States; Mark Lebwohl, MD, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Usha G. Mallya, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
Serious infection events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) Study: Current status of observations Robert Kalb, MD, SUNY at Buffalo, School of Medicine and Biological Sciences, Buffalo, NY, United States; Craig Leonardi, MD, Central Dermatology, St. Louis, MO, United States; Mark Chevrier, MD, PhD, Janssen Services, LLC., Horsham, PA, United States; Mark Lebwohl, MD, Mount Sinai Medical Center, New York, NY, United States Objective: To report the accrual of serious infections in the PSOLAR study.
Background: Secukinumab (AIN457), a fully human antieinterleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at weeks 12 (vs. placebo and etanercept) and 52 (vs. etanercept) for efficacy and safety in subjects with moderate to severe plaque psoriasis. Psoriasis patients frequently report pain, itching, and scaling. Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD) through week 12, which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment. Methods: FIXTURE (NCT01358578) was a randomized, double-blind, active-comparatore and placebo-controlled, multicenter phase 3 study conducted from Jun 2011 to Jun 2013. It consisted of 3 periods: screening (1-4 weeks), induction (12 weeks), and maintenance (40 weeks). Subjects were randomized 1:1:1:1 to 1 of 4 subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, placebo, or etanercept 50 mg. Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. Each item was completed daily using a 0 to 10 numeric rating scale via an e-diary that allowed completion only from 4 PM to 11:45 PM. Focusing on psoriasis-related pain, itching, and scaling, weekly averages were derived for each item, with higher scores indicating greater severity. Time to response was defined as the period from the randomization date to the response date when a prespecified point improvement from baseline had occurred (2.2 points for itching, 2.2 points for pain, and 2.3 points for scaling). Median time to response and percentage of subjects identified as responders for itching, pain, and scaling were estimated using KaplaneMeier methods by treatment group along with a log-rank test, stratified by geographic region and body weight. Hazard ratios were computed using a stratified Cox proportional hazards regression model.
Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of serious infections in PSOLAR overall and by exposure subgroups is reported. Serious infection rates are assessed using definitions of exposure based on treatment at any time or treatment within 91 days preceding the reported event. In cases of exposure to multiple therapies, serious infection events are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled (22,918 cumulative patient-years of follow-up). Unadjusted rates of serious infection, based on exposure within 91 days preceding the event were: ustekinumab 0.89 events per 100 patient years of observation (PYO) [95% CI, 0.59-1.28; 28/3154 PYO], infliximab/golimumab (almost all infliximab) 2.86 per 100PYO [ 95% CI, 2.143.74; 53/1855 PYO], other biologics (almost all etanercept/adalimumab) 1.71 per 100PYO [95% CI, 1.43-2.04; 131/7639 PYO], nonbiologics 1.16 per 100 PYO [95% CI, 0.96-1.39; 119/10271 PYO], and overall 1.44 [95% CI, 1.29-1.61; 331/22918]. Similar rates of serious infection were observed in the analysis of exposure based on treatment received at any time. Limitations: Because of channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments.
Results: PSD data are available for 530 subjects with baseline and at least 1 week postbaseline. Results are expected by Oct 2013 and will be provided in the final presentation.
Conclusions: Unadjusted rates of serious infection show a trend toward lower rates in the ustekinumab group, despite the rules of event attribution, compared to other biologic groups and similar rates to the no biologic group; higher rates were observed in the infliximab/golimumab group. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR represents a powerful resource for tracking safety events of interest, among patients eligible to receive systemic therapies.
Conclusion: Understanding differences in time to relief of these key symptoms for secukinumab, placebo, and etanercept may guide treatment decisions.
Sponsored 100% by Janssen Research & Development, LLC.
Sponsored 100% by Novartis.
P7938 Secukinumab’s time to psoriasis response on patient-reported psoriasis symptoms (ERASURE study) Alice Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; Ari Gnanasakthy, MBA, MS, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; Bruce Strober, MD, University of Connecticut Health Center, Farmington, NJ, United States; Jessica Jie Zhang, MPH, MS, RTI Health Solutions, Research Triangle Park, NC, United States; Mary Helen Tran, PharmD, MBA, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: Secukinumab (AIN457), a fully human antieinterleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at week 12 (vs. placebo) for efficacy and safety in subjects with moderate to severe plaque psoriasis. Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD), which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment. Methods: ERASURE (NCT01365455) was a randomized, double-blind, placebocontrolled, multicenter phase 3 study conducted from Jan 2011 to Feb 2013. It consisted of 4 periods: screening (1-4 weeks), induction (12 weeks), maintenance (40 weeks), and follow-up (8 weeks). Subjects aged ¼ 18 years were randomized 1:1:1 to 1 of 3 subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, or placebo. Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. Each item was completed daily using a 0 to 10 numeric rating scale via an electronic-diary that allowed completion only from 4 PM to 11:45 PM. Weekly averages were derived for each item, with higher scores indicating greater severity. Time to response was defined as the period from the randomization date (first dose) to the response date when a prespecified point improvement from baseline had occurred (2.2 points for itching, 2.2 points for pain, and 2.3 points for scaling). For each item, the CochranMantel-Haenszel test was used to test the statistical hypotheses that there is no difference in the proportion of subjects with a PSD response in any of the secukinumab groups versus placebo separately by week through week 12. Median time to response and percentage of subjects identified as responders for itching, pain, and scaling were estimated using KaplaneMeier methods by treatment group along with a log-rank test, stratified by geographic region and body weight. Hazard ratios were computed using a stratified Cox proportional hazards regression model.
P8331 Short- and long-term treatment of erythrodermic psoriasis with ustekinumab: A national and multicenter case series Marıa Jose Concha-Garz on, MD, Hospital Universitario de la Princesa, Madrid, Spain; Almudena Godoy-Trapero, MD, Hospital Universitario de la Princesa, Madrid, Spain; Esteban Dauden, PhD, Hospital Universitario de la Princesa, Madrid, Spain; J Garcıa, PhD, Hospital General de Valencia, Valencia, Spain; Jose Luis L opez-Estebaranz, PhD, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain; Ofelia Baniandres, PhD, Hospital Universitario Gregorio Mara~ non, Madrid, Spain; Vicente Rocamora, PhD, Hospital de Manacor, Manacor, Spain Introduction: Erythrodermic psoriasis (EP) is a severe form of psoriasis. There is a number of treatment options, but overall there are few evidence-based data because EP is almost always an exclusionary criterion in clinical trials. Ustekinumab (UTK) is a human monoclonal antibody against interleukin-12 and -23 that has been shown as being effective in the treatment of moderate to severe plaque psoriasis. However, data on the use of UTK in EP are limited. The objective of the study is to determine the efficacy and safety of UTK in patients with EP.
Results: PSD data are available for 299 patients; 285 completed at least 1 week postbaseline. Results are expected by Oct 2013 and will be provided in the final presentation. Conclusion: Understanding the patient perspective associated with time to relief of key psoriasis-related symptoms for secukinumab may guide treatment decisions.
Methods: A national, multicentre, retrospective study was performed. Inclusion criteria: (1) patients with erythrodermic psoriasis, defined as involvement of at least 90% of the body surface area (BSA), and (2) patients with at least 12 weeks of followup after initiation treatment with ustekinumab. UTK dosing and schedules were according to the label and guidelines for psoriasis treatments: 45 mg (11 patients) or 90 mg (1 patient) subcutaneously at weeks 0, 4 and then every 12 weeks. Results: Twelve white patients were included (10 males and 2 females; mean age 54.6 years, range 28-79). All patients had received previous systemic therapies including phototherapy (8), acitretin (6), methotrexate (5), cyclosporine (5), infliximab (6), adalimumab (3), etanercept (2), and efalizumab (1). Four patients were naive to biologic treatment. The mean baseline (range) psoriasis area skin index (PASI) and BSA scores were 46 (23-64) and 90.4 (90-95) respectively. At 16 weeks, PASI 50, PASI 75, PASI 90 and PASI 100 were achieved in 11 (92%), 9 (75%), 8 (67%), and 5 (42%) of the 12 patients, respectively. At 48 weeks, PASI 50, PASI 75, PASI 90, and PASI 100 were achieved in 9 (100%), 7 (78%), 5 (55%), and 2 (22%), respectively, of the 9 patients that were evaluated at that time (2 patients did not reach 48 weeks of follow-up, and 1 patient discontinued the therapy because of a loss of efficacy). Three patients needed a shortening in the interval of administration (8-10 weeks) to be effective enough. No severe side effects were observed. Conclusions: Ustekinumab is safe and effective in the short- and long-term treatment of erythrodermic psoriasis, representing a therapeutic alternative for this severe form of the disease.
Sponsored 100% by Novartis.
Commercial support: None identified.
MAY 2014
J AM ACAD DERMATOL
AB189