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Pooled safety and efficacy results from two phase III trials comparing briakinumab with etanercept and placebo for the treatment of moderate to severe psoriasis
P3303
P3305
Pooled safety and efficacy results from two phase III trials comparing briakinumab with etanercept and placebo for the treatment of moderate to severe psoriasis Bruce Strober, New York University School of Medicine, New York, NY, United States; Alice Gottlieb, Tufts Medical Center, Boston, MA, United States; David Williams, Abbott Laboratories, Abbott Park, IL, United States; Yihua Gu, Abbott Laboratories, Abbott Park, IL, United States Background: To provide an integrated analysis of efficacy and safety results from two independent trials comparing briakinumab versus etanercept (ETN) and placebo (pbo) for moderate to severe psoriasis treatment. Methods: Efficacy and safety data were pooled from two 12-week, phase III, doubledummy, randomized trials (NCT00710580, NCT00691964). Patients were randomized 2:2:1 to receive briakinumab (200 mg at weeks 0 and 4, followed by 100 mg at week 8), ETN (50 mg twice weekly), or matching pbo. At week 12, primary efficacy endpoints were percentage of patients achieving a PGA score of ‘‘clear’’ or ‘‘minimal’’ (0/1) and percentage of patients achieving a PASI 75 response. Secondary endpoints included week 12 PASI 90 and PASI 100 response rates. Adverse events (AE) were assessed throughout the study. Nonresponder imputation (NRI) was used to handle missing data. Results: Individual trial results demonstrated superior efficacy of briakinumab versus ETN and pbo (P \.001, briakinumab vs ETN or pbo, both primary endpoints for both studies). For this pooled analysis, data from 697 patients were analyzed: briakinumab, N ¼ 277; ETN, N ¼ 280; pbo, N ¼ 140. At week 12, 71.8%, 34.6%, and 3.6% of briakinumab-, ETN-, and pbo-treated patients, respectively, achieved a PGA 0/1 (P \.001, briakinumab vs ETN or pbo). Week 12 PASI 75 response rates for briakinumab-, ETN-, and pbo-treated patients were 81.2%, 47.9%, and 7.1%, respectively (P \ .001, briakinumab vs ETN or pbo). Week 12 PASI 90 and PASI 100 response rates were 57.4%/18.6%/2.9% and 32.9%/6.4%/0.0% for patients treated with briakinumab/ETN/pbo, respectively (P \.001, briakinumab vs ETN or pbo for both PASI 90 and 100). Serious AE rates were: 2.2%/0.7%/2.1% for briakinumab/ETN/pbo patients. Serious infection rates were: 0.4%/0.4%/0% for briakinumab/ETN/pbo patients. There were no deaths or major adverse cardiovascular events (MACE) in any treatment group.
Effect of ustekinumab on cardiovascular events: Results from pooled phase II and III psoriasis trials K. Gordon, MD, University of Chicago Pritzker School of Medicine/NorthShore University HealthSystems, Chicago, IL, United States; K. Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; P. O. Szapary, MD, Centocor Research and Development, Malvern, PA, United States; R. G. Langley, MD, Dalhousie University, Halifax, Canada Objective: The prevalence of cardiovascular(CV) comorbidities and the risk of major CV events are increased in pts with moderate to severe psoriasis(PsO). We evaluated the impact of ustekinumab (UST) on CV adverse events. Methods: Rates of CV events were evaluated in phase II/III PsO trials including PHOENIX 1 (152 wks, n ¼ 766), PHOENIX 2 (100 wks, n ¼ 1230), ACCEPT (64 wks, n ¼ 903) and 36 wks from phase II (T04, n ¼ 320); all studies are placebo (PBO)controlled except ACCEPT (etanercept-controlled). Nonserious and serious CV events were evaluated during the common PBO-controlled period (through wk 12). Rates of major CV adverse events (MACE), including CV death, nonfatal myocardial infarction, or stroke were used to evaluate risk differences between PBO versus UST during the PBO-controlled period. Overall MACE rates were evaluated with up to 3 years of follow-up. MI/stroke rates were also compared with rates in a general US population based on the Framingham Heart Study, adjusted for selected baseline CV risk factors.
Conclusion: Pooled efficacy results from two independent trials show that briakinumab was superior to ETN and pbo for moderate to severe psoriasis treatment. Serious adverse events were low across all groups and no MACE were observed. Although the safety results of this study appear similar between the two medications, limited patient exposure makes broader safety conclusions incomplete at this time. Commercial support: Funded by Abbott Laboratories.
Results: This analysis included 3117 pts (4782 PYof follow-up),with 1247 pts treated for at least 2 years (median follow-up, 1.7 years). Through wk 12, 4.0% (64/1582) and 4.5% (33/732) of pts in the UST combined and PBO groups, respectively, had [1 serious or nonserious CV events. A numeric imbalance in MACE was observed in the phase II study (4:1 randomization) with three events across the four UST groups versus 0 for PBO. In the two larger PBO-controlled phase III trials (2:1 randomization), two additional MACE events were reported versus 0 for PBO. The pooled phase II/III rate during the PBO-controlled period was 1.23 per 100 PY (95% CI, 0.40-2.87) with a risk difference of 0.3 (95% CI, -0.5 to -1.1). Through 3 years of follow-up, the rate per 100 PY (95% CI) for the UST combined grps was 0.44 (0.27, 0.67). The number of MI and stroke events for the combined UST-treated groups, in up to 3 years of follow-up, was less than what would be expected in the general US population based on the Framingham Study (observed events ¼ 17, expected events ¼ 32.42, SIR ¼ 0.52 [0.31-0.84]). Conclusion: Overall CV adverse event rates were comparable between the UST and PBO-treated grps during the controlled period. The degree of numeric imbalance in MACE events observed in phase II was not reproduced in the overall larger phase III experience. Rates of MACE events with up to 3 years of follow-up were consistent with or lower than expected in the general population. The impact of UST on CV risk will continue to be monitored in ongoing clinical trials and observational registries. Commercial support: Sponsored by Centocor Research and Development.
P3304 An evaluation of the effect of tasocitinib (CP-690,550), an oral Janus kinase inhibitor, on pruritus in patients with plaque psoriasis Carla Mamolo, Pfizer, New London, CT, United States; Andrew Bushmakin, Pfizer, New London, CT, United States; Jane Harness, Pfizer, Niantic, CT, United States; Joseph Cappelleri, Pfizer, New London, CT, United States; Michelle Stewart, Pfizer, New London, CT, United States Background: Pruritus is a frequent and irritating symptom of psoriasis. The effect of oral tasocitinib (CP-690,550) on pruritus in patients with moderate-to-severe plaque psoriasis was evaluated. Methods: In a 12-week, double-blind, placebo-controlled phase IIb trial, adult patients (n ¼ 197) with moderate-to-severe psoriasis were randomized to tasocitinib (2, 5, or 15 mg BID) or placebo. Pruritus was assessed using the Itch Severity Item (ISI), a 0 (‘‘no itching’’) to 10 (‘‘worst possible itching’’) scale administered daily for the first 2 weeks of treatment (using a patient diary), and then administered at 2- or 4week intervals until the end of treatment. A repeated-measures longitudinal model was used to estimate mean changes in ISI scores over time for treatment group comparisons. An anchor-based approach, with Patient Global Assessment as the anchor, was used to define the clinically important difference (CID) and clinically important responder (CIR) on the ISI. Results: At baseline, mean (SD) ISI scores for patients in the tasocitinib 2, 5, and 15 mg BID and placebo groups were 7.04 (2.65), 6.98 (2.27), 6.96 (2.23), and 6.78 (2.77), respectively, indicating a moderate-to-high level of itch severity. A significant decrease in ISI score (improvement in itch severity) was observed as early as day 3. The estimated CID (95% confidence interval) for the ISI was 1.6 (1.5; 1.8) points; the CIR rate was 29.8% (23.3; 36.4). By day 10, all active treatment groups showed significant and clinically meaningful mean decreases in ISI scores (placebo-adjusted changes from baseline of 2.05, 1.82, 2.47, respectively, for 2, 5, and 15 mg BID; all P \.001). Significant and clinically meaningful mean decreases in ISI scores continued through week 12 for all active treatment groups (placebo-adjusted changes from baseline of 3.86, 3.75, and 5.14 respectively for 2, 5, and 15 mg BID, all P\.0001). At week 12, 87% to 100% of patients in the active treatment groups could be considered CIRs versus 29% of patients in the placebo group (P \ .05). Tasocitinib was generally efficacious and well-tolerated, with the most frequent adverse events being upper respiratory tract infections and headache.
P3306 Calcipotriene foam is an effective treatment for plaque-type psoriasis Steve Feldman, MD, PhD, Wake Forest University Health Sciences, Winston Salem, NC, United States; George Li, Stiefel, a GSK company, Research Triangle Park, NC, United States; Melody Wyres, Stiefel, a GSK company, Palo Alto, CA, United States; Merrie Van Syoc, Stiefel, a GSK company, Palo Alto, CA, United States; Steve Kempers, MD, Minnesota Clinical Study Center, Fridley, MN, United States Objectives: A calcipotriene 0.005% foam has been developed to provide convenient, localized application for plaque-type psoriasis. In two phase III studies, a greater percentage of subjects with plaque-type psoriasis achieved global treatment success, defined as having an ISGA score of clear (0) or almost clear (1) and a minimum improvement in the ISGA score of two grades from baseline to week 8. The secondary objective of these studies was to describe the effects of treatment on target lesions. Methods: Two phase III, multicenter, double-blind studies randomized 659 subjects 12 years of age and older with mild to moderate plaque-type psoriasis. Subjects were instructed to apply calcipotriene foam (n ¼ 437) or vehicle foam (n ¼ 222) twicedaily for 8 weeks to all affected psoriatic areas of the body, excluding those on the face and scalp. Target lesion erythema, scaling, and plaque thickness were assessed, and target lesion clearing success was defined as having a target lesion score of (0) or (1) at week 8 plus at least a two-grade improvement from baseline to week 8 for erythema and scaling and a target lesion score of 0 plus at least a two-grade improvement from baseline to week 8 for plaque thickness.
Conclusion: In patients with psoriasis, tasocitinib produces significant and rapid reduction in pruritus, as measured by the ISI, with severity continuing to diminish over 12 weeks of treatment. The reduction in pruritus observed with tasocitinib is clinically meaningful for the vast majority of patients.
Results: The percentage of subjects with a score of 0 (no erythema) or 1 (faint erythema) plus a two-grade improvement in the erythema score from baseline at week 8 was 25% for calcipotriene foam versus 15% for vehicle foam; 31% and 18% versus 20% and 10%, respectively, in each study. The percentage of subjects with a score of 0 (no evidence of scaling) or 1 (minimal evidence of scaling) plus a twograde improvement in the scaling score from baseline at week 8 was 27% for calcipotriene foam versus 15% for vehicle foam; 34% and 22% versus 18% and 11%, respectively, in each study. The percentage of subjects with a score of 0 (no elevation in plaque thickness over normal skin) was 16% versus 8% for calcipotriene foam and vehicle foam, respectively; 20% and 13% versus 11% and 4%, respectively, in each study. Conclusions: Calcipotriene foam used twice-daily for up to 8 weeks was effective in achieving target lesion improvement as assessed by improvement in erythema, scaling, and plaque thickness.
Commercial support: 100% sponsored by Pfizer.
Commercial support: 100% sponsored by Stiefel, a GSK company.
AB146
J AM ACAD DERMATOL
FEBRUARY 2011
P3305
Pooled safety and efficacy results from two phase III trials comparing briakinumab with etanercept and placebo for the treatment of moderate to severe psoriasis Bruce Strober, New York University School of Medicine, New York, NY, United States; Alice Gottlieb, Tufts Medical Center, Boston, MA, United States; David Williams, Abbott Laboratories, Abbott Park, IL, United States; Yihua Gu, Abbott Laboratories, Abbott Park, IL, United States Background: To provide an integrated analysis of efficacy and safety results from two independent trials comparing briakinumab versus etanercept (ETN) and placebo (pbo) for moderate to severe psoriasis treatment. Methods: Efficacy and safety data were pooled from two 12-week, phase III, doubledummy, randomized trials (NCT00710580, NCT00691964). Patients were randomized 2:2:1 to receive briakinumab (200 mg at weeks 0 and 4, followed by 100 mg at week 8), ETN (50 mg twice weekly), or matching pbo. At week 12, primary efficacy endpoints were percentage of patients achieving a PGA score of ‘‘clear’’ or ‘‘minimal’’ (0/1) and percentage of patients achieving a PASI 75 response. Secondary endpoints included week 12 PASI 90 and PASI 100 response rates. Adverse events (AE) were assessed throughout the study. Nonresponder imputation (NRI) was used to handle missing data. Results: Individual trial results demonstrated superior efficacy of briakinumab versus ETN and pbo (P \.001, briakinumab vs ETN or pbo, both primary endpoints for both studies). For this pooled analysis, data from 697 patients were analyzed: briakinumab, N ¼ 277; ETN, N ¼ 280; pbo, N ¼ 140. At week 12, 71.8%, 34.6%, and 3.6% of briakinumab-, ETN-, and pbo-treated patients, respectively, achieved a PGA 0/1 (P \.001, briakinumab vs ETN or pbo). Week 12 PASI 75 response rates for briakinumab-, ETN-, and pbo-treated patients were 81.2%, 47.9%, and 7.1%, respectively (P \ .001, briakinumab vs ETN or pbo). Week 12 PASI 90 and PASI 100 response rates were 57.4%/18.6%/2.9% and 32.9%/6.4%/0.0% for patients treated with briakinumab/ETN/pbo, respectively (P \.001, briakinumab vs ETN or pbo for both PASI 90 and 100). Serious AE rates were: 2.2%/0.7%/2.1% for briakinumab/ETN/pbo patients. Serious infection rates were: 0.4%/0.4%/0% for briakinumab/ETN/pbo patients. There were no deaths or major adverse cardiovascular events (MACE) in any treatment group.
Effect of ustekinumab on cardiovascular events: Results from pooled phase II and III psoriasis trials K. Gordon, MD, University of Chicago Pritzker School of Medicine/NorthShore University HealthSystems, Chicago, IL, United States; K. Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; P. O. Szapary, MD, Centocor Research and Development, Malvern, PA, United States; R. G. Langley, MD, Dalhousie University, Halifax, Canada Objective: The prevalence of cardiovascular(CV) comorbidities and the risk of major CV events are increased in pts with moderate to severe psoriasis(PsO). We evaluated the impact of ustekinumab (UST) on CV adverse events. Methods: Rates of CV events were evaluated in phase II/III PsO trials including PHOENIX 1 (152 wks, n ¼ 766), PHOENIX 2 (100 wks, n ¼ 1230), ACCEPT (64 wks, n ¼ 903) and 36 wks from phase II (T04, n ¼ 320); all studies are placebo (PBO)controlled except ACCEPT (etanercept-controlled). Nonserious and serious CV events were evaluated during the common PBO-controlled period (through wk 12). Rates of major CV adverse events (MACE), including CV death, nonfatal myocardial infarction, or stroke were used to evaluate risk differences between PBO versus UST during the PBO-controlled period. Overall MACE rates were evaluated with up to 3 years of follow-up. MI/stroke rates were also compared with rates in a general US population based on the Framingham Heart Study, adjusted for selected baseline CV risk factors.
Conclusion: Pooled efficacy results from two independent trials show that briakinumab was superior to ETN and pbo for moderate to severe psoriasis treatment. Serious adverse events were low across all groups and no MACE were observed. Although the safety results of this study appear similar between the two medications, limited patient exposure makes broader safety conclusions incomplete at this time. Commercial support: Funded by Abbott Laboratories.
Results: This analysis included 3117 pts (4782 PYof follow-up),with 1247 pts treated for at least 2 years (median follow-up, 1.7 years). Through wk 12, 4.0% (64/1582) and 4.5% (33/732) of pts in the UST combined and PBO groups, respectively, had [1 serious or nonserious CV events. A numeric imbalance in MACE was observed in the phase II study (4:1 randomization) with three events across the four UST groups versus 0 for PBO. In the two larger PBO-controlled phase III trials (2:1 randomization), two additional MACE events were reported versus 0 for PBO. The pooled phase II/III rate during the PBO-controlled period was 1.23 per 100 PY (95% CI, 0.40-2.87) with a risk difference of 0.3 (95% CI, -0.5 to -1.1). Through 3 years of follow-up, the rate per 100 PY (95% CI) for the UST combined grps was 0.44 (0.27, 0.67). The number of MI and stroke events for the combined UST-treated groups, in up to 3 years of follow-up, was less than what would be expected in the general US population based on the Framingham Study (observed events ¼ 17, expected events ¼ 32.42, SIR ¼ 0.52 [0.31-0.84]). Conclusion: Overall CV adverse event rates were comparable between the UST and PBO-treated grps during the controlled period. The degree of numeric imbalance in MACE events observed in phase II was not reproduced in the overall larger phase III experience. Rates of MACE events with up to 3 years of follow-up were consistent with or lower than expected in the general population. The impact of UST on CV risk will continue to be monitored in ongoing clinical trials and observational registries. Commercial support: Sponsored by Centocor Research and Development.
P3304 An evaluation of the effect of tasocitinib (CP-690,550), an oral Janus kinase inhibitor, on pruritus in patients with plaque psoriasis Carla Mamolo, Pfizer, New London, CT, United States; Andrew Bushmakin, Pfizer, New London, CT, United States; Jane Harness, Pfizer, Niantic, CT, United States; Joseph Cappelleri, Pfizer, New London, CT, United States; Michelle Stewart, Pfizer, New London, CT, United States Background: Pruritus is a frequent and irritating symptom of psoriasis. The effect of oral tasocitinib (CP-690,550) on pruritus in patients with moderate-to-severe plaque psoriasis was evaluated. Methods: In a 12-week, double-blind, placebo-controlled phase IIb trial, adult patients (n ¼ 197) with moderate-to-severe psoriasis were randomized to tasocitinib (2, 5, or 15 mg BID) or placebo. Pruritus was assessed using the Itch Severity Item (ISI), a 0 (‘‘no itching’’) to 10 (‘‘worst possible itching’’) scale administered daily for the first 2 weeks of treatment (using a patient diary), and then administered at 2- or 4week intervals until the end of treatment. A repeated-measures longitudinal model was used to estimate mean changes in ISI scores over time for treatment group comparisons. An anchor-based approach, with Patient Global Assessment as the anchor, was used to define the clinically important difference (CID) and clinically important responder (CIR) on the ISI. Results: At baseline, mean (SD) ISI scores for patients in the tasocitinib 2, 5, and 15 mg BID and placebo groups were 7.04 (2.65), 6.98 (2.27), 6.96 (2.23), and 6.78 (2.77), respectively, indicating a moderate-to-high level of itch severity. A significant decrease in ISI score (improvement in itch severity) was observed as early as day 3. The estimated CID (95% confidence interval) for the ISI was 1.6 (1.5; 1.8) points; the CIR rate was 29.8% (23.3; 36.4). By day 10, all active treatment groups showed significant and clinically meaningful mean decreases in ISI scores (placebo-adjusted changes from baseline of 2.05, 1.82, 2.47, respectively, for 2, 5, and 15 mg BID; all P \.001). Significant and clinically meaningful mean decreases in ISI scores continued through week 12 for all active treatment groups (placebo-adjusted changes from baseline of 3.86, 3.75, and 5.14 respectively for 2, 5, and 15 mg BID, all P\.0001). At week 12, 87% to 100% of patients in the active treatment groups could be considered CIRs versus 29% of patients in the placebo group (P \ .05). Tasocitinib was generally efficacious and well-tolerated, with the most frequent adverse events being upper respiratory tract infections and headache.
P3306 Calcipotriene foam is an effective treatment for plaque-type psoriasis Steve Feldman, MD, PhD, Wake Forest University Health Sciences, Winston Salem, NC, United States; George Li, Stiefel, a GSK company, Research Triangle Park, NC, United States; Melody Wyres, Stiefel, a GSK company, Palo Alto, CA, United States; Merrie Van Syoc, Stiefel, a GSK company, Palo Alto, CA, United States; Steve Kempers, MD, Minnesota Clinical Study Center, Fridley, MN, United States Objectives: A calcipotriene 0.005% foam has been developed to provide convenient, localized application for plaque-type psoriasis. In two phase III studies, a greater percentage of subjects with plaque-type psoriasis achieved global treatment success, defined as having an ISGA score of clear (0) or almost clear (1) and a minimum improvement in the ISGA score of two grades from baseline to week 8. The secondary objective of these studies was to describe the effects of treatment on target lesions. Methods: Two phase III, multicenter, double-blind studies randomized 659 subjects 12 years of age and older with mild to moderate plaque-type psoriasis. Subjects were instructed to apply calcipotriene foam (n ¼ 437) or vehicle foam (n ¼ 222) twicedaily for 8 weeks to all affected psoriatic areas of the body, excluding those on the face and scalp. Target lesion erythema, scaling, and plaque thickness were assessed, and target lesion clearing success was defined as having a target lesion score of (0) or (1) at week 8 plus at least a two-grade improvement from baseline to week 8 for erythema and scaling and a target lesion score of 0 plus at least a two-grade improvement from baseline to week 8 for plaque thickness.
Conclusion: In patients with psoriasis, tasocitinib produces significant and rapid reduction in pruritus, as measured by the ISI, with severity continuing to diminish over 12 weeks of treatment. The reduction in pruritus observed with tasocitinib is clinically meaningful for the vast majority of patients.
Results: The percentage of subjects with a score of 0 (no erythema) or 1 (faint erythema) plus a two-grade improvement in the erythema score from baseline at week 8 was 25% for calcipotriene foam versus 15% for vehicle foam; 31% and 18% versus 20% and 10%, respectively, in each study. The percentage of subjects with a score of 0 (no evidence of scaling) or 1 (minimal evidence of scaling) plus a twograde improvement in the scaling score from baseline at week 8 was 27% for calcipotriene foam versus 15% for vehicle foam; 34% and 22% versus 18% and 11%, respectively, in each study. The percentage of subjects with a score of 0 (no elevation in plaque thickness over normal skin) was 16% versus 8% for calcipotriene foam and vehicle foam, respectively; 20% and 13% versus 11% and 4%, respectively, in each study. Conclusions: Calcipotriene foam used twice-daily for up to 8 weeks was effective in achieving target lesion improvement as assessed by improvement in erythema, scaling, and plaque thickness.
Commercial support: 100% sponsored by Pfizer.
Commercial support: 100% sponsored by Stiefel, a GSK company.
AB146
J AM ACAD DERMATOL
FEBRUARY 2011