- Email: [email protected]
ABT-874 versus methotrexate in moderate to severe psoriasis: Effects on health-related quality-of-life outcomes
P3343
P3345
Bilateral comparison study on the order of application of combination clobetasol proprionate spray and calcitriol ointment in the treatment of plaque psoriasis Michelle Henry, MD, Mount Sinai School of Medicine, New York, NY, United States; Amylynne Frankel, MD, Mount Sinai School of Medicine, New York, NY, United States; Jason Emer, MD, Mount Sinai School of Medicine, New York, NY, United States; Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, United States
Sustained efficacy of ustekinumab for the treatment of moderate to severe psoriasis in initial responders continuing with maintenance therapy through year 3 K. Gordon, MD, University of Chicago Pritzker School of Medicine/NorthShore University HealthSystems, Chicago, IL, United States; D. Baker, MD, Baker Allergy, Asthma and Dermatology Research Center, Lake Oswego, OR, United States; L. Guenther, MD, The Guenther Dermatology and Research Centre, London, Canada; N. Yeilding, MD, Centocor Research and Development, Malvern, PA, United States
Background: Psoriasis is an inflammatory skin condition with significant morbidity that has a prevalence of 1% to 3% worldwide. Common treatments for limited disease include topical medications such as corticosteroids and vitamin D analogues. Combination regimens have demonstrated synergistic efficacy while limiting the side effects of each individual therapy, although no studies have determined if the order of application of these therapies affect clinical outcome. Objective: To evaluate whether the order of application affects the efficacy of a combination treatment with clobetasol propionate spray and calcitriol ointment in mild to moderate plaque psoriasis. Methods: This was an investigator-blinded bilateral comparison study in 13 subjects (n ¼ 13) with mild to moderate plaque psoriasis defined by at least ‘‘mild’’ (2) intensity by the signs of psoriasis scale (erythema, scale, induration). Subjects were randomized into one of two treatment arms (ratio 1:1). One arm was instructed to apply clobetasol spray first followed by the calcitriol ointment to target lesions on the right side of the body, and calcitriol ointment first followed by clobetasol spray to target lesions on the left side of the body. The other arm was instructed to do the reverse. Treatment was applied twice daily for 4 weeks and patients were evaluated at weeks 0, 2, and 4. Assessments included the signs of psoriasis and photography. Results: Thirteen subjects (n ¼ 13) were enrolled and 10 (n ¼ 10) successfully completed the trial. Three subjects (n ¼ 3) withdrew because of failure to comply with study protocol. There was no statistically significant difference between the signs of psoriasis clinical assessments of erythema (P ¼ .22), scale (P ¼ .28), and induration (P ¼ .37) for either order of application. Upon averaging assessment values, both order of applications were equally effective (P ¼.39). No cutaneous side effects were noted. Conclusion: Combination therapy with clobetasol spray and calcitriol ointment is efficacious in the treatment of mild to moderate psoriasis regardless of order of application. Commercial support: 100% sponsored by Galderma.
Background: Ustekinumab (UST), a fully human monoclonal antibody against the p40 subunit of interleukins 12 and 23, has shown significant efficacy in treating pts with moderate to severe plaque psoriasis (PsO) in clinical trials. Objective: To assess long-term efficacy of q12 week maintenance therapy with UST in initial responders to treatment in the PHOENIX1 trial. Methods: Long-term safety and efficacy of UST were evaluated in a randomized withdrawal population of initial responders with up to 3 years of treatment in the PHOENIX1 double-blind, placebo controlled trial. Pts originally randomized to UST who achieved Psoriasis Area and Severity Index (PASI)75 at weeks 28 and 40 were rerandomized at week 40 to continue receiving the same dose of UST q12 weeks (n ¼ 162) or placebo (n ¼ 160). Pts withdrawn from UST reinitiated treatment after losing 50% of the improvement gained while on treatment. Results: Baseline demographic and clinical characteristics were comparable among all rerandomized groups. At week 40, 66% of the PASI75 responders on 45-mg UST and 73% of those on 90-mg achieved PASI90, and 64% and 84%, respectively, had a Physician’s Global Assessment (PGA) score of clear or minimal. At week 148, 82% and 87% in the 45- and 90-mg groups, respectively, had PASI75, 96% and 98% PASI50, 43% and 62% PASI90, and 53% and 63% PGA of clear or minimal responses. The median percent improvement in PASI score from baseline remained stable between weeks 40 and 148, ranging from 87% to 91% in the 45-mg group and 94% to 97% in the 90-mg group. Response rates of pts withdrawn from therapy at Wk40 progressively decreased with time; no cases of rebound were seen. Long-term use of UST was generally well tolerated. After rerandomization, 87% and 83% of pts maintained on 45-mg and 90-mg UST dosing, respectively, experienced $ 1 AE versus 93% and 92% of pts that interrupted dosing; 3.9% and 3.6% of pts maintained on 45-mg and 90-mg UST dosing experienced $ 1 serious AE versus 5.5% and 10.3% of pts that interrupted therapy; and 5.2% and 4.8% of pts maintained on 45-mg and 90-mg UST dosing discontinued treatment because of an AE versus 5.5% and 3.4% of pts that interrupted therapy. Conclusion: Clinical responses to UST were durable and generally sustained at high and stable rates in responders that continued q12 week maintenance therapy through week 148, while pts withdrawn from therapy lost response over time. Commercial support: This study and the printing of the poster is sponsored by Centocor Research and Development.
P3344 ABT-874 versus methotrexate in moderate to severe psoriasis: Effects on health-related quality-of-life outcomes Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany; Magda Tsaneva, Analysis Group, Boston, MA, United States; Murali Sundaram, Abbott Laboratories, Abbott Park, IL, United States; Yanjun Bao, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess effects of treatment with ABT-874 versus methotrexate (MTX) on health-related quality of life (HRQOL) in patients with moderate to severe psoriasis. Methods: In this 52-week double-blind trial, patients were randomized to ABT-874 (200 mg at weeks 0 and 4, and 100 mg every 4 weeks from weeks 8-48) or MTX (5-25 mg weekly). Nonresponding patients were discontinued from the study. Nonresponse was defined as \75% improvement in the Psoriasis Area and Severity Index (PASI) and a Physician’s Global Assessment (PGA) score of ‘‘mild’’ or worse at week 24 or PASI\50 improvement and a PGA score of ‘‘severe’’ or worse after week 24. HRQOL outcomes, including the Dermatology Life Quality Index (DLQI), visual analog scales for Ps-related pain (VAS-Ps), and EuroQOL 5D Index (EQ5DeIndex) score, were assessed at baseline and during follow-up. Lower DLQI and VAS scores and higher EQ-5DeIndex scores indicated better HRQOL. Analyses of covariance were used to compare mean improvements from baseline to weeks 12 and 52, with last observations carried forward for missing values. Percentages of patients with improvement $ the minimum clinically important difference (MCID response) and percentages of patients achieving DLQI # 1 were compared using chi-squared tests and nonresponder imputations for missing values. Results: At week 12, the ABT-874 group (N ¼ 154) had significantly (P \.05) greater percentages of patients achieving MCID response versus the MTX group (N ¼ 163) in DLQI (70.1% vs 50.9%), VAS-Ps (49.4% vs 35.0%), and EQ-5DeIndex (57.1% vs 43.6%). Mean improvements at week 12 were also significantly greater in the ABT874 group for DLQI (-8.88 vs -6.00), VAS-Ps (-23.38 vs -17.84), and EQ-5DeIndex (0.20 vs 0.14) (all P \.05). At week 52, ABT-874 versus MTX was associated with significantly greater MCID response rates for DLQI (56.5% vs 18.4%), VAS-Ps (38.3% vs 11.0%), and EQ-5DeIndex (48.7% vs 17.2%) and with significantly greater mean improvements from baseline in these measures (-9.62 vs -6.54 for DLQI, -24.30 vs -17.81 for VAS-Ps, and 0.24 vs 0.15 for EQ-5DeIndex). A significantly greater percentage of patients in the ABT-874 group versus the MTX group achieved DLQI # 1 at week 24 (70.8% vs 34.4%) and week 52 (61.7% vs 17.8%) (P \.05). Conclusion: ABT-874 treatment for moderate to severe psoriasis was associated with significantly greater and clinically meaningful improvements in HRQOL outcomes compared with MTX at both 12 and 52 weeks of treatment. Commercial support: This study was funded by Abbott Laboratories.
AB156
J AM ACAD DERMATOL
P3346 Ustekinumab improves overall skin response and health-related quality of life in a subset of moderate to severe psoriasis patients with psoriatic arthritis: Analysis of PHOENIX 1 and 2 H. Sofen, MD, Dermatology Associates, Los Angeles, CA, United States; N. Wasel, MD, Stratica Medical, Edmonton, Canada; N. Yeilding, MD, Centocor Research and Development, Malvern, PA, United States; S. Lee, MPH, Johnson and Johnson Pharmaceutical Services, Horsham, PA, United States Objective: Ustekinumab (UST) has been shown to improve psoriasis (PsO) and health-related quality of life (HRQoL) in patients (pts) with moderate to severe PsO. This analysis examines the effects of UST on overall skin response and the impact on HRQoL in a subset of PsO pts with psoriatic arthritis (PsA). Methods: In PHOENIX 1 and 2, pts with moderate to severe PsO (n ¼ 1996) were randomized to UST 45 mg or 90 mg at weeks 0, 4, and q12 week thereafter, or placebo (PBO) at weeks 0 and 4 with crossover to UST at week 12. PsA was identified in pts by medical history. PsO severity was assessed using the Psoriasis Area and Severity Index (PASI) and HRQoL with the Dermatology Life Quality Index (DLQI). Results: At baseline, 563 (28.2%) pts had PsA. The mean PASI was 20.7 (SD ¼ 8.4) and the mean DLQI was 12.6 (SD ¼ 7.2), indicating significant poor quality of life. At week 12, UST-treated pts had a significantly greater percent improvement in mean PASI score than PBO-treated pts (45 mg: 73.7%, 90 mg: 75.3%, PBO: 2.4%; P \.001). A significantly greater portion of UST-treated pts achieved PASI75 compared to PBOtreated pts (45 mg: 63.0%, 90 mg: 61.5%, PBO: 3.6%; P \.001). UST-treated pts had a significantly greater decrease (improvement) in DLQI score at week 12 than PBOtreated pts (45 mg: -9.2 [SD ¼ 7.1], 90mg: -9.7 [SD ¼ 6.6], PBO: -0.01 [SD ¼ 5.0]; P\ .001). At week 12, 70.2% in the UST 45-mg group and 75.0% in the UST 90-mg group, respectively, experienced $ 5 point improvement in DLQI compared to 15.6 % for the PBO group (P \.001). UST-treated pts (50.0% and 57.1% in the 45-mg and 90-mg groups, respectively) had a DLQI score of 0 or 1, indicating no impact of the disease or treatment on quality of life compared with 1.0% of PBO-treated pts (P \.001). Conclusion: UST improved overall skin response and HRQoL in a subset of moderate to severe PsO pts with PsA. This finding will be further evaluated in various ongoing phase III studies. Commercial support: This study and the printing of the poster is sponsored by Centocor Research and Development.
FEBRUARY 2011
P3345
Bilateral comparison study on the order of application of combination clobetasol proprionate spray and calcitriol ointment in the treatment of plaque psoriasis Michelle Henry, MD, Mount Sinai School of Medicine, New York, NY, United States; Amylynne Frankel, MD, Mount Sinai School of Medicine, New York, NY, United States; Jason Emer, MD, Mount Sinai School of Medicine, New York, NY, United States; Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, United States
Sustained efficacy of ustekinumab for the treatment of moderate to severe psoriasis in initial responders continuing with maintenance therapy through year 3 K. Gordon, MD, University of Chicago Pritzker School of Medicine/NorthShore University HealthSystems, Chicago, IL, United States; D. Baker, MD, Baker Allergy, Asthma and Dermatology Research Center, Lake Oswego, OR, United States; L. Guenther, MD, The Guenther Dermatology and Research Centre, London, Canada; N. Yeilding, MD, Centocor Research and Development, Malvern, PA, United States
Background: Psoriasis is an inflammatory skin condition with significant morbidity that has a prevalence of 1% to 3% worldwide. Common treatments for limited disease include topical medications such as corticosteroids and vitamin D analogues. Combination regimens have demonstrated synergistic efficacy while limiting the side effects of each individual therapy, although no studies have determined if the order of application of these therapies affect clinical outcome. Objective: To evaluate whether the order of application affects the efficacy of a combination treatment with clobetasol propionate spray and calcitriol ointment in mild to moderate plaque psoriasis. Methods: This was an investigator-blinded bilateral comparison study in 13 subjects (n ¼ 13) with mild to moderate plaque psoriasis defined by at least ‘‘mild’’ (2) intensity by the signs of psoriasis scale (erythema, scale, induration). Subjects were randomized into one of two treatment arms (ratio 1:1). One arm was instructed to apply clobetasol spray first followed by the calcitriol ointment to target lesions on the right side of the body, and calcitriol ointment first followed by clobetasol spray to target lesions on the left side of the body. The other arm was instructed to do the reverse. Treatment was applied twice daily for 4 weeks and patients were evaluated at weeks 0, 2, and 4. Assessments included the signs of psoriasis and photography. Results: Thirteen subjects (n ¼ 13) were enrolled and 10 (n ¼ 10) successfully completed the trial. Three subjects (n ¼ 3) withdrew because of failure to comply with study protocol. There was no statistically significant difference between the signs of psoriasis clinical assessments of erythema (P ¼ .22), scale (P ¼ .28), and induration (P ¼ .37) for either order of application. Upon averaging assessment values, both order of applications were equally effective (P ¼.39). No cutaneous side effects were noted. Conclusion: Combination therapy with clobetasol spray and calcitriol ointment is efficacious in the treatment of mild to moderate psoriasis regardless of order of application. Commercial support: 100% sponsored by Galderma.
Background: Ustekinumab (UST), a fully human monoclonal antibody against the p40 subunit of interleukins 12 and 23, has shown significant efficacy in treating pts with moderate to severe plaque psoriasis (PsO) in clinical trials. Objective: To assess long-term efficacy of q12 week maintenance therapy with UST in initial responders to treatment in the PHOENIX1 trial. Methods: Long-term safety and efficacy of UST were evaluated in a randomized withdrawal population of initial responders with up to 3 years of treatment in the PHOENIX1 double-blind, placebo controlled trial. Pts originally randomized to UST who achieved Psoriasis Area and Severity Index (PASI)75 at weeks 28 and 40 were rerandomized at week 40 to continue receiving the same dose of UST q12 weeks (n ¼ 162) or placebo (n ¼ 160). Pts withdrawn from UST reinitiated treatment after losing 50% of the improvement gained while on treatment. Results: Baseline demographic and clinical characteristics were comparable among all rerandomized groups. At week 40, 66% of the PASI75 responders on 45-mg UST and 73% of those on 90-mg achieved PASI90, and 64% and 84%, respectively, had a Physician’s Global Assessment (PGA) score of clear or minimal. At week 148, 82% and 87% in the 45- and 90-mg groups, respectively, had PASI75, 96% and 98% PASI50, 43% and 62% PASI90, and 53% and 63% PGA of clear or minimal responses. The median percent improvement in PASI score from baseline remained stable between weeks 40 and 148, ranging from 87% to 91% in the 45-mg group and 94% to 97% in the 90-mg group. Response rates of pts withdrawn from therapy at Wk40 progressively decreased with time; no cases of rebound were seen. Long-term use of UST was generally well tolerated. After rerandomization, 87% and 83% of pts maintained on 45-mg and 90-mg UST dosing, respectively, experienced $ 1 AE versus 93% and 92% of pts that interrupted dosing; 3.9% and 3.6% of pts maintained on 45-mg and 90-mg UST dosing experienced $ 1 serious AE versus 5.5% and 10.3% of pts that interrupted therapy; and 5.2% and 4.8% of pts maintained on 45-mg and 90-mg UST dosing discontinued treatment because of an AE versus 5.5% and 3.4% of pts that interrupted therapy. Conclusion: Clinical responses to UST were durable and generally sustained at high and stable rates in responders that continued q12 week maintenance therapy through week 148, while pts withdrawn from therapy lost response over time. Commercial support: This study and the printing of the poster is sponsored by Centocor Research and Development.
P3344 ABT-874 versus methotrexate in moderate to severe psoriasis: Effects on health-related quality-of-life outcomes Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany; Magda Tsaneva, Analysis Group, Boston, MA, United States; Murali Sundaram, Abbott Laboratories, Abbott Park, IL, United States; Yanjun Bao, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess effects of treatment with ABT-874 versus methotrexate (MTX) on health-related quality of life (HRQOL) in patients with moderate to severe psoriasis. Methods: In this 52-week double-blind trial, patients were randomized to ABT-874 (200 mg at weeks 0 and 4, and 100 mg every 4 weeks from weeks 8-48) or MTX (5-25 mg weekly). Nonresponding patients were discontinued from the study. Nonresponse was defined as \75% improvement in the Psoriasis Area and Severity Index (PASI) and a Physician’s Global Assessment (PGA) score of ‘‘mild’’ or worse at week 24 or PASI\50 improvement and a PGA score of ‘‘severe’’ or worse after week 24. HRQOL outcomes, including the Dermatology Life Quality Index (DLQI), visual analog scales for Ps-related pain (VAS-Ps), and EuroQOL 5D Index (EQ5DeIndex) score, were assessed at baseline and during follow-up. Lower DLQI and VAS scores and higher EQ-5DeIndex scores indicated better HRQOL. Analyses of covariance were used to compare mean improvements from baseline to weeks 12 and 52, with last observations carried forward for missing values. Percentages of patients with improvement $ the minimum clinically important difference (MCID response) and percentages of patients achieving DLQI # 1 were compared using chi-squared tests and nonresponder imputations for missing values. Results: At week 12, the ABT-874 group (N ¼ 154) had significantly (P \.05) greater percentages of patients achieving MCID response versus the MTX group (N ¼ 163) in DLQI (70.1% vs 50.9%), VAS-Ps (49.4% vs 35.0%), and EQ-5DeIndex (57.1% vs 43.6%). Mean improvements at week 12 were also significantly greater in the ABT874 group for DLQI (-8.88 vs -6.00), VAS-Ps (-23.38 vs -17.84), and EQ-5DeIndex (0.20 vs 0.14) (all P \.05). At week 52, ABT-874 versus MTX was associated with significantly greater MCID response rates for DLQI (56.5% vs 18.4%), VAS-Ps (38.3% vs 11.0%), and EQ-5DeIndex (48.7% vs 17.2%) and with significantly greater mean improvements from baseline in these measures (-9.62 vs -6.54 for DLQI, -24.30 vs -17.81 for VAS-Ps, and 0.24 vs 0.15 for EQ-5DeIndex). A significantly greater percentage of patients in the ABT-874 group versus the MTX group achieved DLQI # 1 at week 24 (70.8% vs 34.4%) and week 52 (61.7% vs 17.8%) (P \.05). Conclusion: ABT-874 treatment for moderate to severe psoriasis was associated with significantly greater and clinically meaningful improvements in HRQOL outcomes compared with MTX at both 12 and 52 weeks of treatment. Commercial support: This study was funded by Abbott Laboratories.
AB156
J AM ACAD DERMATOL
P3346 Ustekinumab improves overall skin response and health-related quality of life in a subset of moderate to severe psoriasis patients with psoriatic arthritis: Analysis of PHOENIX 1 and 2 H. Sofen, MD, Dermatology Associates, Los Angeles, CA, United States; N. Wasel, MD, Stratica Medical, Edmonton, Canada; N. Yeilding, MD, Centocor Research and Development, Malvern, PA, United States; S. Lee, MPH, Johnson and Johnson Pharmaceutical Services, Horsham, PA, United States Objective: Ustekinumab (UST) has been shown to improve psoriasis (PsO) and health-related quality of life (HRQoL) in patients (pts) with moderate to severe PsO. This analysis examines the effects of UST on overall skin response and the impact on HRQoL in a subset of PsO pts with psoriatic arthritis (PsA). Methods: In PHOENIX 1 and 2, pts with moderate to severe PsO (n ¼ 1996) were randomized to UST 45 mg or 90 mg at weeks 0, 4, and q12 week thereafter, or placebo (PBO) at weeks 0 and 4 with crossover to UST at week 12. PsA was identified in pts by medical history. PsO severity was assessed using the Psoriasis Area and Severity Index (PASI) and HRQoL with the Dermatology Life Quality Index (DLQI). Results: At baseline, 563 (28.2%) pts had PsA. The mean PASI was 20.7 (SD ¼ 8.4) and the mean DLQI was 12.6 (SD ¼ 7.2), indicating significant poor quality of life. At week 12, UST-treated pts had a significantly greater percent improvement in mean PASI score than PBO-treated pts (45 mg: 73.7%, 90 mg: 75.3%, PBO: 2.4%; P \.001). A significantly greater portion of UST-treated pts achieved PASI75 compared to PBOtreated pts (45 mg: 63.0%, 90 mg: 61.5%, PBO: 3.6%; P \.001). UST-treated pts had a significantly greater decrease (improvement) in DLQI score at week 12 than PBOtreated pts (45 mg: -9.2 [SD ¼ 7.1], 90mg: -9.7 [SD ¼ 6.6], PBO: -0.01 [SD ¼ 5.0]; P\ .001). At week 12, 70.2% in the UST 45-mg group and 75.0% in the UST 90-mg group, respectively, experienced $ 5 point improvement in DLQI compared to 15.6 % for the PBO group (P \.001). UST-treated pts (50.0% and 57.1% in the 45-mg and 90-mg groups, respectively) had a DLQI score of 0 or 1, indicating no impact of the disease or treatment on quality of life compared with 1.0% of PBO-treated pts (P \.001). Conclusion: UST improved overall skin response and HRQoL in a subset of moderate to severe PsO pts with PsA. This finding will be further evaluated in various ongoing phase III studies. Commercial support: This study and the printing of the poster is sponsored by Centocor Research and Development.
FEBRUARY 2011