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Safety of ustekinumab from the placebo-controlled periods of psoriatic arthritis and psoriasis clinical developmental programs
P7843
P7617
Safety and efficacy of calcipotriene plus betamethasone dipropionate topical suspension in adolescents with scalp psoriasis: An open, noncontrolled, 8-week trial Melinda Gooderham, MD, Skin Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada; Merle Kurvits, MS, LEO Pharma A/S, Ballerup, Denmark; Zhenyi Xu, MD, LEO Pharma A/S, Ballerup, Denmark Background: About one-third of psoriasis cases present during childhood or adolescence. Most children and adolescents have fairly limited disease and can be managed with appropriate use of topical therapies, but the impact on quality of life, self-esteem, school functioning, relationships, and physical and psychological development is significant. Efficacy and safety of the fixed combination of calcipotriene plus betamethasone dipropionate topical suspension (C/BD) in plaque psoriasis on body and scalp has been shown in adult patients, but validated clinical data from treatment of adolescents is limited. Aims: To investigate the safety and efficacy of C/BD applied once daily for up to 8 weeks in adolescents with scalp psoriasis, as the second of 2 separate, parallel trials.
Safety profile of ixekizumab, an antieIL-17 monoclonal antibody, in chronic plaque psoriasis patients after at least 1 year of open label treatment Kenneth Gordon, MD, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States; Craig Leonardi, MD, St. Louis University School of Medicine, St. Louis, MO, United States; Daniel Braun, MD, Eli Lilly and Company, Indianapolis, IN, United States; Gregory Cameron, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Janelle Erickson, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Mark Lebwohl, MD, The Mount Sinai School of Medicine, New York, NY, United States; Michael Heffernan, MD, Eli Lilly and Company, Indianapolis, IN, United States; Subhashis Banerjee, MD, Eli Lilly and Company, Indianapolis, IN, United States Background: Ixekizumab is a humanized monoclonal antibody that neutralizes IL17A shown to be effective for treating moderate to severe chronic plaque psoriasis in a phase 2 study. Longer term safety was evaluated with an open-label extension (OLE) of this study with a minimum of 52 additional weeks of treatment. Methods: In the phase 2 study, 142 pts were randomized to treatment with ixekizumab (10, 25, 75, or 150 mg) or placebo at 0, 2, 4, 8, 12, and 16 weeks. Pts were eligible to enter the OLE at Week 32 or when responses were \ PASI 75. Pts entering the OLE were treated with 120 mg ixekizumab every 4 weeks. Safety was assessed by monitoring adverse events (AE), serious AEs (SAE), vital signs, standard laboratory measures and adverse events of special interest (AESI). In this interim analysis, safety data is included through 52 weeks for all pts in the OLE. Additional preliminary data through week 100 are reported for patients with additional exposure at the time of the analysis.
Methods: This was a prospective, noncontrolled, multicenter trial conducted in Canada, France, and the United Kingdom. Subjects aged 12-17 years with moderate to severe scalp psoriasis affecting at least 10% of the scalp area were included. Safety was the primary objective and was assessed in terms of adverse drug reactions and change from baseline in serum and urinary calcium. Efficacy assessments included Investigator’s Global Assessment of disease severity (IGA), Total Sign Score (TSS; sum of scores for redness, thickness and scaliness), Patient’s Global Assessment of disease severity (PaGA), and Patient’s Assessment of Itching. Results: A total of 78 subjects (35 boys and 43 girls) with a median age of 15 years were assigned treatment. Mean extent of psoriasis was 43.7% of the scalp area, and 74.4% and 25.6% of subjects had moderate and severe/very severe scalp psoriasis, respectively. Five subjects reported adverse drug reactions and there were no serious adverse events. No cases of hypercalcaemia were reported and there were no relevant changes in urinary calcium. At end of treatment, 84.6% were clear or almost clear on the IGA. The mean % improvement in TSS from baseline to end of treatment was 80.4%. In total, 87.2% of subjects rated their scalp psoriasis as clear or very mild and 96.2% had no or mild itching compared to 17.9% at baseline. Conclusions: C/BD topical suspension was well tolerated with no effect on calcium metabolism in adolescents with scalp psoriasis. In this open trial, C/BD appeared to be highly efficacious as rated by investigators and subjects including a significant improvement of itching, all of which similar to what has been shown in adults. Sponsored 100% by LEO Pharma A/S.
Results: Of the 120 pts who entered the OLE, 103 remained on therapy after 52 weeks. Of the 17 pts who discontinued, 4 were for AEs, 2 of which were SAEs (urinary tract obstruction and hidradenitis), and 3 were for lack of efficacy. There were 67% pts with treatment-emergent AEs (TEAEs). Of those occurring in ¼ 2.5% of pts, infections (nasopharyngitis and upper respiratory infections) were the most common and most were mild to moderate. Other notable TEAEs were cellulitis (4), urinary tract infections (4), candidiasis (2 oral and 2 vaginal), and injection site reactions (2). Allergic reaction/hypersensitivies were observed in 4 pts. There were 2 reports of Grade 3 increase in ALT and no Grade 3 neutropenia. No clinically significant changes were observed in vital signs. A total of 13 SAEs were reported for 10 pts. Notable SAEs were cardiac disorders (3: acute coronary syndrome, arteriosclerosis, CHF), cellulitis (1), pyelonephritis (1), rectal cancer (1) and skin disorder (1: hidradenitis). Conclusions: We report over 1 year of additional safety data from an OLE of a phase 2 trial of ixekizumab. To date, ixekizumab has been well tolerated and most AEs were mild to moderate. Five large phase III studies with ixekizumab will provide further data on its long-term safety. Sponsored 100% by Eli Lilly and Company.
P7918 Safety of ustekinumab from the placebo-controlled periods of psoriatic arthritis and psoriasis clinical developmental programs Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; Alan Mendelsohn, MD, Janssen Research & Development, LLC, Spring House, PA, United States; Alice Gottlieb, MD, Tufts Medical Center, Boston, MA, United States; Daphne Chan, PhD, Janssen Research & Development, LLC, Spring House, PA, United States Objectives: To describe safety experience of UST during double-blind, PBOcontrolled portion of the psoriatic arthritis (PsA) & psoriasis (PsO) clinical programs. Methods: Safety data for PsA population were pooled from 1 Ph2 & 2 Ph3 (PSUMMIT I & II) studies in pts with active PsA; for PsO population from 1 Ph2 (n ¼ 320) & 2 Ph3 (PHOENIX 1 & 2) studies in pts with moderate to severe PsO, including a subgrp with documented PsA (history/current) at baseline (BL). Pts were randomized to PBO/UST45mg/UST90mg. PBO-controlled period was 16wks for PsA studies, 20wks for Ph2 PsO study and 12wks for Ph3 PsO studies. Concomitant therapies were permitted in PsA studies but not in the PsO studies. Safety event rates were compared between PBO & UST grps within each population (PSA, PSA subgrp, PSO). Data for UST dose grps were analyzed as a combined grp. All pts who received ¼ 1 dose were included. Results reported as number of events per 100 pt-yrs of follow-up (PY). Results: 1071 treated pts (379 PBO [110 PY], 692 UST [209 PY]) were included in PsA population & 2314 treated pts (732 PBO [177 PY], 1582 UST [407 PY]) were included in PsO population (including 207 PBO [49 PY], 421 UST [106 PY] in PsA sub-grp). BL demographics & medical history were generally comparable between PsA & PsO populations. Within each population, rates of overall AEs, infections, & SAEs in pts receiving PBO or UST were generally comparable. AEs per 100PY (PBO vs. UST): PsA studies 348.07 vs. 375.83, PsO studies 413.24 vs. 502.91, PsA sub-grp 476.42 vs. 481.32. Infections per 100PY (PBO vs. UST): PsA studies 110.59 vs. 100.06, PsO studies 142.79 vs. 141.16, PsA sub-grp 139.89 vs. 142.79. A slightly higher rate of SAEs was observed in the PBO grp in PsA population; SAEs per 100PY (PBO vs. UST): PsA studies 12.69 vs. 5.75, PsO studies 6.78 vs. 7.62, PsA sub-grp 4.05 vs. 6.62. Slightly higher rates of AEs leading to d/c were observed across all PBO grps; AEs leading to d/c per 100PY (PBO vs. UST): PsA studies 13.79 vs. 3.85, PsO studies 9.74 vs. 5.95, PsA sub-grp 12.37 vs. 5.71. Serious infections, NMSC, other malignancies, and MACE were generally comparable, with overlapping confidence intervals, between the PBO & UST grps within the PsA & PsO populations. Conclusions: During the PBO-controlled period, overall safety observations were consistent between both populations and safety event rates were generally comparable between pts receiving PBO and UST within each population. Sponsored 100% by Janssen Research & Development, LLC.
AB184
J AM ACAD DERMATOL
P8417 Secukinumab autoinjectors demonstrate patient satisfaction: An analysis of the Self-Injection Assessment Questionnaire (SIAQ) in the JUNCTURE Study Katharina Kreutzer, MD, St€adtische Kliniken Bielefeld, Bielefeld, Germany; JeanPhilippe Lacour, MD, Dermatology Department, Nice, France; Ruquan You, MS, Beijing Novartis Pharma Co. Ltd., Shanghai, China; Usha G. Mallya, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: JUNCTURE (NCT01636687) was the first study to test autoinjector (AI)-administered secukinumab (AIN457), a fully human anti-interleukin 17A monoclonal antibody, in the treatment of plaque-type psoriasis. The study evaluated the efficacy of secukinumab (150 and 300 mg) administered subcutaneously (SC) versus placebo at week 12 and the long-term efficacy, safety, and tolerability of the secukinumab liquid when used for 52 weeks. Patient satisfaction was assessed with a self-administered Self-Injection Assessment Questionnaire (SIAQ). Methods: JUNCTURE was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study conducted between Oct 2012 and Apr 2013. Subjects were randomized 1:1:1 to 1 of 3 treatment arms: secukinumab 150 mg or 300 mg SC once weekly for 4 weeks, then once every 4 weeks from week 4 through week 48, or matching placebo. Subjects were trained to self-inject via AI and self-administered the study drug in the appropriate injection site at the study site (2 injections per visit). The SIAQ measures overall subject experience with SC self-injection before the first self-injection and after dosing on the domains of feelings about injections, self-confidence, satisfaction with self-injection, injection-site reactions, ease of use, and self-image. The SIAQ was completed at baseline and weeks 1, 4, 8, 12, 24, 36, and 48. Subjects rated each item of the SIAQ on a 5-point scale: 1 (worst experience) to 5 (best experience). Scores were transformed to 0 (worst experience) to 10 (best experience). Summary statistics for the domain scores and item scores will be provided by visit and treatment group. Item and domain scores from the module taken before the first self-injection at baseline will be compared with those from the module taken after the 2 self-injections. Results: SIAQ data were available for 182 subjects. Scores for feelings about selfinjections, self-confidence, and satisfaction with self-injections improved from baseline to week 12 for all groups. Mean absolute increases (baseline to week 12) were 1.00 (7.81 to 8.82), 1.47 (7.40 to 8.88), and 2.35 (6.68 to 9.03), respectively. Results up to week 48 are expected in January 2014 and will be provided in the final presentation. Conclusions: Patient satisfaction with administration mode is an important consideration for a chronic disease such as psoriasis. Results from this study suggest usability and patient satisfaction with secukinumab AI in the study subjects. Sponsored by Novartis Pharmaceuticals (100%).
MAY 2014
P7617
Safety and efficacy of calcipotriene plus betamethasone dipropionate topical suspension in adolescents with scalp psoriasis: An open, noncontrolled, 8-week trial Melinda Gooderham, MD, Skin Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada; Merle Kurvits, MS, LEO Pharma A/S, Ballerup, Denmark; Zhenyi Xu, MD, LEO Pharma A/S, Ballerup, Denmark Background: About one-third of psoriasis cases present during childhood or adolescence. Most children and adolescents have fairly limited disease and can be managed with appropriate use of topical therapies, but the impact on quality of life, self-esteem, school functioning, relationships, and physical and psychological development is significant. Efficacy and safety of the fixed combination of calcipotriene plus betamethasone dipropionate topical suspension (C/BD) in plaque psoriasis on body and scalp has been shown in adult patients, but validated clinical data from treatment of adolescents is limited. Aims: To investigate the safety and efficacy of C/BD applied once daily for up to 8 weeks in adolescents with scalp psoriasis, as the second of 2 separate, parallel trials.
Safety profile of ixekizumab, an antieIL-17 monoclonal antibody, in chronic plaque psoriasis patients after at least 1 year of open label treatment Kenneth Gordon, MD, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States; Craig Leonardi, MD, St. Louis University School of Medicine, St. Louis, MO, United States; Daniel Braun, MD, Eli Lilly and Company, Indianapolis, IN, United States; Gregory Cameron, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Janelle Erickson, PhD, Eli Lilly and Company, Indianapolis, IN, United States; Mark Lebwohl, MD, The Mount Sinai School of Medicine, New York, NY, United States; Michael Heffernan, MD, Eli Lilly and Company, Indianapolis, IN, United States; Subhashis Banerjee, MD, Eli Lilly and Company, Indianapolis, IN, United States Background: Ixekizumab is a humanized monoclonal antibody that neutralizes IL17A shown to be effective for treating moderate to severe chronic plaque psoriasis in a phase 2 study. Longer term safety was evaluated with an open-label extension (OLE) of this study with a minimum of 52 additional weeks of treatment. Methods: In the phase 2 study, 142 pts were randomized to treatment with ixekizumab (10, 25, 75, or 150 mg) or placebo at 0, 2, 4, 8, 12, and 16 weeks. Pts were eligible to enter the OLE at Week 32 or when responses were \ PASI 75. Pts entering the OLE were treated with 120 mg ixekizumab every 4 weeks. Safety was assessed by monitoring adverse events (AE), serious AEs (SAE), vital signs, standard laboratory measures and adverse events of special interest (AESI). In this interim analysis, safety data is included through 52 weeks for all pts in the OLE. Additional preliminary data through week 100 are reported for patients with additional exposure at the time of the analysis.
Methods: This was a prospective, noncontrolled, multicenter trial conducted in Canada, France, and the United Kingdom. Subjects aged 12-17 years with moderate to severe scalp psoriasis affecting at least 10% of the scalp area were included. Safety was the primary objective and was assessed in terms of adverse drug reactions and change from baseline in serum and urinary calcium. Efficacy assessments included Investigator’s Global Assessment of disease severity (IGA), Total Sign Score (TSS; sum of scores for redness, thickness and scaliness), Patient’s Global Assessment of disease severity (PaGA), and Patient’s Assessment of Itching. Results: A total of 78 subjects (35 boys and 43 girls) with a median age of 15 years were assigned treatment. Mean extent of psoriasis was 43.7% of the scalp area, and 74.4% and 25.6% of subjects had moderate and severe/very severe scalp psoriasis, respectively. Five subjects reported adverse drug reactions and there were no serious adverse events. No cases of hypercalcaemia were reported and there were no relevant changes in urinary calcium. At end of treatment, 84.6% were clear or almost clear on the IGA. The mean % improvement in TSS from baseline to end of treatment was 80.4%. In total, 87.2% of subjects rated their scalp psoriasis as clear or very mild and 96.2% had no or mild itching compared to 17.9% at baseline. Conclusions: C/BD topical suspension was well tolerated with no effect on calcium metabolism in adolescents with scalp psoriasis. In this open trial, C/BD appeared to be highly efficacious as rated by investigators and subjects including a significant improvement of itching, all of which similar to what has been shown in adults. Sponsored 100% by LEO Pharma A/S.
Results: Of the 120 pts who entered the OLE, 103 remained on therapy after 52 weeks. Of the 17 pts who discontinued, 4 were for AEs, 2 of which were SAEs (urinary tract obstruction and hidradenitis), and 3 were for lack of efficacy. There were 67% pts with treatment-emergent AEs (TEAEs). Of those occurring in ¼ 2.5% of pts, infections (nasopharyngitis and upper respiratory infections) were the most common and most were mild to moderate. Other notable TEAEs were cellulitis (4), urinary tract infections (4), candidiasis (2 oral and 2 vaginal), and injection site reactions (2). Allergic reaction/hypersensitivies were observed in 4 pts. There were 2 reports of Grade 3 increase in ALT and no Grade 3 neutropenia. No clinically significant changes were observed in vital signs. A total of 13 SAEs were reported for 10 pts. Notable SAEs were cardiac disorders (3: acute coronary syndrome, arteriosclerosis, CHF), cellulitis (1), pyelonephritis (1), rectal cancer (1) and skin disorder (1: hidradenitis). Conclusions: We report over 1 year of additional safety data from an OLE of a phase 2 trial of ixekizumab. To date, ixekizumab has been well tolerated and most AEs were mild to moderate. Five large phase III studies with ixekizumab will provide further data on its long-term safety. Sponsored 100% by Eli Lilly and Company.
P7918 Safety of ustekinumab from the placebo-controlled periods of psoriatic arthritis and psoriasis clinical developmental programs Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; Alan Mendelsohn, MD, Janssen Research & Development, LLC, Spring House, PA, United States; Alice Gottlieb, MD, Tufts Medical Center, Boston, MA, United States; Daphne Chan, PhD, Janssen Research & Development, LLC, Spring House, PA, United States Objectives: To describe safety experience of UST during double-blind, PBOcontrolled portion of the psoriatic arthritis (PsA) & psoriasis (PsO) clinical programs. Methods: Safety data for PsA population were pooled from 1 Ph2 & 2 Ph3 (PSUMMIT I & II) studies in pts with active PsA; for PsO population from 1 Ph2 (n ¼ 320) & 2 Ph3 (PHOENIX 1 & 2) studies in pts with moderate to severe PsO, including a subgrp with documented PsA (history/current) at baseline (BL). Pts were randomized to PBO/UST45mg/UST90mg. PBO-controlled period was 16wks for PsA studies, 20wks for Ph2 PsO study and 12wks for Ph3 PsO studies. Concomitant therapies were permitted in PsA studies but not in the PsO studies. Safety event rates were compared between PBO & UST grps within each population (PSA, PSA subgrp, PSO). Data for UST dose grps were analyzed as a combined grp. All pts who received ¼ 1 dose were included. Results reported as number of events per 100 pt-yrs of follow-up (PY). Results: 1071 treated pts (379 PBO [110 PY], 692 UST [209 PY]) were included in PsA population & 2314 treated pts (732 PBO [177 PY], 1582 UST [407 PY]) were included in PsO population (including 207 PBO [49 PY], 421 UST [106 PY] in PsA sub-grp). BL demographics & medical history were generally comparable between PsA & PsO populations. Within each population, rates of overall AEs, infections, & SAEs in pts receiving PBO or UST were generally comparable. AEs per 100PY (PBO vs. UST): PsA studies 348.07 vs. 375.83, PsO studies 413.24 vs. 502.91, PsA sub-grp 476.42 vs. 481.32. Infections per 100PY (PBO vs. UST): PsA studies 110.59 vs. 100.06, PsO studies 142.79 vs. 141.16, PsA sub-grp 139.89 vs. 142.79. A slightly higher rate of SAEs was observed in the PBO grp in PsA population; SAEs per 100PY (PBO vs. UST): PsA studies 12.69 vs. 5.75, PsO studies 6.78 vs. 7.62, PsA sub-grp 4.05 vs. 6.62. Slightly higher rates of AEs leading to d/c were observed across all PBO grps; AEs leading to d/c per 100PY (PBO vs. UST): PsA studies 13.79 vs. 3.85, PsO studies 9.74 vs. 5.95, PsA sub-grp 12.37 vs. 5.71. Serious infections, NMSC, other malignancies, and MACE were generally comparable, with overlapping confidence intervals, between the PBO & UST grps within the PsA & PsO populations. Conclusions: During the PBO-controlled period, overall safety observations were consistent between both populations and safety event rates were generally comparable between pts receiving PBO and UST within each population. Sponsored 100% by Janssen Research & Development, LLC.
AB184
J AM ACAD DERMATOL
P8417 Secukinumab autoinjectors demonstrate patient satisfaction: An analysis of the Self-Injection Assessment Questionnaire (SIAQ) in the JUNCTURE Study Katharina Kreutzer, MD, St€adtische Kliniken Bielefeld, Bielefeld, Germany; JeanPhilippe Lacour, MD, Dermatology Department, Nice, France; Ruquan You, MS, Beijing Novartis Pharma Co. Ltd., Shanghai, China; Usha G. Mallya, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: JUNCTURE (NCT01636687) was the first study to test autoinjector (AI)-administered secukinumab (AIN457), a fully human anti-interleukin 17A monoclonal antibody, in the treatment of plaque-type psoriasis. The study evaluated the efficacy of secukinumab (150 and 300 mg) administered subcutaneously (SC) versus placebo at week 12 and the long-term efficacy, safety, and tolerability of the secukinumab liquid when used for 52 weeks. Patient satisfaction was assessed with a self-administered Self-Injection Assessment Questionnaire (SIAQ). Methods: JUNCTURE was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study conducted between Oct 2012 and Apr 2013. Subjects were randomized 1:1:1 to 1 of 3 treatment arms: secukinumab 150 mg or 300 mg SC once weekly for 4 weeks, then once every 4 weeks from week 4 through week 48, or matching placebo. Subjects were trained to self-inject via AI and self-administered the study drug in the appropriate injection site at the study site (2 injections per visit). The SIAQ measures overall subject experience with SC self-injection before the first self-injection and after dosing on the domains of feelings about injections, self-confidence, satisfaction with self-injection, injection-site reactions, ease of use, and self-image. The SIAQ was completed at baseline and weeks 1, 4, 8, 12, 24, 36, and 48. Subjects rated each item of the SIAQ on a 5-point scale: 1 (worst experience) to 5 (best experience). Scores were transformed to 0 (worst experience) to 10 (best experience). Summary statistics for the domain scores and item scores will be provided by visit and treatment group. Item and domain scores from the module taken before the first self-injection at baseline will be compared with those from the module taken after the 2 self-injections. Results: SIAQ data were available for 182 subjects. Scores for feelings about selfinjections, self-confidence, and satisfaction with self-injections improved from baseline to week 12 for all groups. Mean absolute increases (baseline to week 12) were 1.00 (7.81 to 8.82), 1.47 (7.40 to 8.88), and 2.35 (6.68 to 9.03), respectively. Results up to week 48 are expected in January 2014 and will be provided in the final presentation. Conclusions: Patient satisfaction with administration mode is an important consideration for a chronic disease such as psoriasis. Results from this study suggest usability and patient satisfaction with secukinumab AI in the study subjects. Sponsored by Novartis Pharmaceuticals (100%).
MAY 2014