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Adalimumab treatment for moderate psoriasis reduces the risk of transitioning to severe psoriasis
P3377
P3379
Comorbidities of psoriasis have an independent effect on impairing patient health-related quality of life and work productivity Bruce Strober, MD, New York University School of Medicine, New York, NY, United States; Annie Guerin, Analysis Group, Boston, MA, United States; Parvez Mulani, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories, Abbott Park, IL, United States
Safety events in moderate to severe psoriasis patients treated with efalizumab Alison Ehrlich, MD, George Washington University, Washington, DC, United States; Ivor Caro, MD, Genentech, Inc, South San Francisco, CA, United States; Winifred Werther, Genentech, Inc, South San Francisco, CA, United States; Yun Chen, PhD, Genentech, Inc, South San Francisco, CA, United States
Objective: Psoriasis (Ps) is a chronic recurrent inflammatory skin disorder that impairs patient health-related quality of life (HRQOL) and work productivity. This study investigated whether comorbidities of Ps have independent effects on HRQOL and work productivity, adjusting for Ps severity. Methods: The study pooled patient (pt) populations with moderate (10 # PASI # 20) and severe (PASI[20) Ps from one phase II (M02-528) and two phase III trials (CHAMPION and REVEAL) of adalimumab. Study outcomes included the Dermatology Life Quality Index (DLQI), the SF-36 Mental and Physical Component Score (MCS and PCS), and the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP). Different samples were used to assess the impact of comorbidity on each outcome based on pt data available per clinical trial. Outcomes were compared between pts with at least one major comorbidity (ie, depression, psoriatic arthritis, angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, coronary artery disease, hypertension, arthritis, diabetes, hyperlipidemia, or obesity) and pts without these comorbidities. In addition, Ps pts with and without psoriatic arthritis (PsA) or depression were compared. Wilcoxon rank sum tests were used for descriptive comparisons. The incremental effect of the comorbidities was analyzed with analysis of covariance controlled for age, sex, race, and baseline PASI score. Results: Sample sizes for baseline measures included: DLQI (n ¼ 1585), SF-36 MCS and PCS (n ¼ 1314), and WPAI-SHP (n ¼ 847). The presence of any major comorbidity significantly impaired pt HRQOL and work productivity compared with pts not having comorbidities. There were significant differences between groups in DLQI (0.90; P ¼.012), WPAI-SHP (4.40; P ¼ .016), SF-36 MCS (1.90; P ¼ .007), and PCS (5.60; P \ .001) scores. There was a statistically significant and clinically meaningful difference in SF-36 MCS score in Ps pts with depression compared with those without it (7.96; P \ .001). Similarly, in Ps pts with PsA, a statistically significant and clinically meaningful decline in SF-36 PCS score (7.10; P \.001) was observed compared with those without PsA. Conclusion: The presence of at least one major comorbidity, depression, or PsA significantly impaired pt HRQOL and work productivity, independent of Ps severity.
Introduction: Moderate to severe psoriasis patients may have an increased risk for selected safety events including malignancies and infections. To measure the magnitude of this risk, we measured the risk of safety events in psoriasis cohorts identified in a health care database and in efalizumab-treated psoriasis patients enrolled in an observational study. Methods: Patients with and without psoriasis who were at least 18 years old were identified in the i3 LabRx (UnitedHealthcare) database during 2002 to 2005. Patients with $ 1 psoriasis diagnosis and $ 1 psoriasis therapy prescription (ultraviolet light, systemic, or biologic) were classified to the treated or moderate to severe psoriasis (SP) cohort and all other patients with at least one psoriasis diagnosis were classified to the untreated or mild psoriasis (MP) cohort. The nonpsoriasis cohort (NP) was a random sample of patients from the database who did not have a psoriasis diagnosis. Efalizumab-treated patients were identified from the Raptiva Epidemiologic Study of Psoriasis Outcomes and Safety Events (RESPONSE). Safety outcomes defined as malignancy, nonmelanoma skin cancer, infections, psoriasis, inflammatory/autoimmune diseases, thrombocytopenia, and hepatic events were identified using emergency department or inpatient hospital codes in the health care database and using Medical Dictionary for Regulatory Activities (MedDRA) coding of serious adverse events in RESPONSE. Results: We identified 43,739 SP, 89,492 MP, and 2,227,968 NP patients in LabRx and 1206 efalizumab-treated patients in RESPONSE. Incidence rates of malignancies were 19.1 (95% CI, 18.0-20.3), 10.6 (10.0-11.3), and 11.1 (11.0-11.2) per 1000 person years in the SP, MP, and NP cohorts, respectively. The incidence rate of malignancies in efalizumab-treated patients was 17.7 (95% CI, 11.4-26.1) per 1000 person years. Incidence rates of infections were 40.0 (95% CI, 38.3-41.8), 20.9 (95% CI, 20.1-21.8), and 20.7 (95% CI, 20.6-20.9) per 1000 person years in the SP, MP, and NP cohorts, respectively. The incidence rate of infections in efalizumab-treated patients was 21.6 (95% CI, 14.6-32.0) per 1000 person years. Results for other safety events will be shown. Conclusions: The risk of selected safety events in the moderate to severe psoriasis cohort was higher than the mild psoriasis or nonpsoriasis cohorts of the health care database. Risk of these safety events in efalizumab-treated psoriasis patients appears to be within the range expected based on the moderate to severe psoriasis cohort.
Commercial support: 100% sponsored by Abbott. Commercial support: Sponsored by Genentech, Inc.
P3378 Adalimumab treatment for moderate psoriasis reduces the risk of transitioning to severe psoriasis Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; James Signorovitch, PhD, Analysis Group, Inc, Boston, MA, United States; Parvzez Mulani, PhD, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, PharmD, MPH, Abbott Laboratories, Abbott Park, IL, United States Objectives: Without appropriate treatment, patients (pts) with moderate psoriasis (Ps) can experience worsening symptoms and transition to severe Ps. The efficacy of adalimumab (ADA) in reducing Ps symptoms has been established for pts with moderate to severe Ps. The aims of this study were to determine the risk of transitioning to severe Ps among placebo-treated pts with moderate Ps, and to evaluate whether ADA treatment of pts with moderate Ps can prevent transition to severe Ps. Methods: Pts with moderate Ps (ie, 10 # PASI # 20 and Physician’s Global Assessment [PGA] of ‘‘moderate’’) at baseline were identified from two phase III, randomized, placebo-controlled trials (CHAMPION and REVEAL). During the trials’ initial 16-week double-blind treatment periods, PASI and PGA were evaluated at weeks 0, 1, 2, 4, 8, 12, and 16 or at early termination. A transition to severe Ps was defined as a follow-up visit with a PASI score [20 that had increased by $ 25% from baseline and PGA of ‘‘severe’’ or ‘‘very severe.’’ The cumulative incidence of pts transitioning to severe Ps was estimated using the KaplaneMeier (KM) method and compared for ADA versus placebo using a log-rank test. At week 16, pts who transitioned to severe Ps were compared to those who had not in terms of their Dermatology Life Quality Index (DLQI) and their Ps/psoriatic arthritis (PsA)-related pain.
P3380 A phase IV randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of efalizumab in patients with moderate to severe plaque psoriasis involving the scalp Leon Kircik, MD, Physicians Skin Care, Louisville, KY, United States; Ivor Caro, MD, Genentech, Inc, South San Francisco, CA, United States; Joel Schlessinger, MD, Skin Specialists, Omaha, Nebraska, United States; Yun Chen, PhD, Genentech, Inc, South San Francisco, CA, United States Introduction: This is a phase IV randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of subcutaneous (SC) efalizumab in adult patients ( $ 18 yrs of age) with chronic moderate to severe plaque psoriasis with involvement of the scalp who have had no previous exposure to efalizumab.
Conclusions: Placebo-treated pts with moderate Ps had a high 17-week risk of transitioning to severe Ps. Transitions to severe Ps were associated with significantly greater impairment of dermatologic quality of life and increased pain. The risk of transitioning from moderate to severe Ps was almost eliminated by ADA treatment.
Methods: The study consists of a screening period, a double-blind treatment period, an open-label treatment period, and an observation/follow-up period. The planned enrollment is 100 patients—67 in the efalizumab arm and 33 in the placebo arm. The patient’s plaque psoriasis must affect at least 30% of the scalp and the scalp psoriasis must have at least one of the following symptoms: erythema, desquamation, or induration. If the patient has psoriasis that involves only the scalp and nowhere else on the body, the patient may be eligible for the study if, in the investigator’s opinion, the plaque psoriasis is considered moderate to severe by Physician’s Global Assessment (PGA) and meets the minimum requirements. The primary objective is to evaluate the efficacy of a 12-week course of SC efalizumab compared with placebo in adults ( $ 18 yrs of age) with chronic moderate to severe plaque psoriasis involving the scalp, as measured by the proportion of patients achieving a $ 75% decrease of Psoriasis Scalp Severity Index (PSS) relative to day 0. Several secondary endpoints will also evaluate the efficacy of efalizumab. These will include PSSI-75 and PSSI-50; the proportion of patients achieving a PGA rating of clear (0), almost clear (1), or mild (2) at 12 and 24 weeks; Scalpdex, a quality of life instrument for scalp dermatoses; and an assessment of patient-reported scalp itch. Results: Currently, 121 patients have been screened and 83 patients have been enrolled in the study at 33 sites in the United States. Full enrollment is expected by August 2008. Conclusions: The results of this study will be the first from a placebo-controlled study that specifically addresses the efficacy of efalizumab on the treatment of scalp psoriasis. This presentation will include data from the first 12 weeks of the study.
Commercial support: 100% sponsored by Abbott.
Commercial support: Sponsored by Genentech, Inc.
Results: Among pts with moderate Ps at baseline (placebo, n ¼ 207; ADA, n ¼ 406), 21.3% (44/207) of placebo-treated pts and 2.2% (9/406) of ADA-treated pts transitioned to severe Ps, without adjusting for early dropout. By week 17, the KM-estimated risk of transitioning to severe Ps was 32.5% (95% CI, 20.0-49.8%) for placebo-treated pts and 2.3% (95% CI, 1.2-4.3%) for ADA-treated pts. The estimated hazard reduction of transitioning to severe Ps was 91.0% (95% CI, 81.3-95.5%) for ADA versus placebo. Compared with pts whose Ps remained moderate, pts who transitioned to severe Ps experienced, at week 16, more Ps/PsA-related pain by 39.9 (95% CI, 33.5-46.3) units on a scale of 0 to 100, and worse DLQI scores, by 9.4 units (95% CI, 7.9-10.8) on a scale of 0 to 30.
MARCH 2009
J AM ACAD DERMATOL
AB181
P3379
Comorbidities of psoriasis have an independent effect on impairing patient health-related quality of life and work productivity Bruce Strober, MD, New York University School of Medicine, New York, NY, United States; Annie Guerin, Analysis Group, Boston, MA, United States; Parvez Mulani, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories, Abbott Park, IL, United States
Safety events in moderate to severe psoriasis patients treated with efalizumab Alison Ehrlich, MD, George Washington University, Washington, DC, United States; Ivor Caro, MD, Genentech, Inc, South San Francisco, CA, United States; Winifred Werther, Genentech, Inc, South San Francisco, CA, United States; Yun Chen, PhD, Genentech, Inc, South San Francisco, CA, United States
Objective: Psoriasis (Ps) is a chronic recurrent inflammatory skin disorder that impairs patient health-related quality of life (HRQOL) and work productivity. This study investigated whether comorbidities of Ps have independent effects on HRQOL and work productivity, adjusting for Ps severity. Methods: The study pooled patient (pt) populations with moderate (10 # PASI # 20) and severe (PASI[20) Ps from one phase II (M02-528) and two phase III trials (CHAMPION and REVEAL) of adalimumab. Study outcomes included the Dermatology Life Quality Index (DLQI), the SF-36 Mental and Physical Component Score (MCS and PCS), and the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP). Different samples were used to assess the impact of comorbidity on each outcome based on pt data available per clinical trial. Outcomes were compared between pts with at least one major comorbidity (ie, depression, psoriatic arthritis, angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, coronary artery disease, hypertension, arthritis, diabetes, hyperlipidemia, or obesity) and pts without these comorbidities. In addition, Ps pts with and without psoriatic arthritis (PsA) or depression were compared. Wilcoxon rank sum tests were used for descriptive comparisons. The incremental effect of the comorbidities was analyzed with analysis of covariance controlled for age, sex, race, and baseline PASI score. Results: Sample sizes for baseline measures included: DLQI (n ¼ 1585), SF-36 MCS and PCS (n ¼ 1314), and WPAI-SHP (n ¼ 847). The presence of any major comorbidity significantly impaired pt HRQOL and work productivity compared with pts not having comorbidities. There were significant differences between groups in DLQI (0.90; P ¼.012), WPAI-SHP (4.40; P ¼ .016), SF-36 MCS (1.90; P ¼ .007), and PCS (5.60; P \ .001) scores. There was a statistically significant and clinically meaningful difference in SF-36 MCS score in Ps pts with depression compared with those without it (7.96; P \ .001). Similarly, in Ps pts with PsA, a statistically significant and clinically meaningful decline in SF-36 PCS score (7.10; P \.001) was observed compared with those without PsA. Conclusion: The presence of at least one major comorbidity, depression, or PsA significantly impaired pt HRQOL and work productivity, independent of Ps severity.
Introduction: Moderate to severe psoriasis patients may have an increased risk for selected safety events including malignancies and infections. To measure the magnitude of this risk, we measured the risk of safety events in psoriasis cohorts identified in a health care database and in efalizumab-treated psoriasis patients enrolled in an observational study. Methods: Patients with and without psoriasis who were at least 18 years old were identified in the i3 LabRx (UnitedHealthcare) database during 2002 to 2005. Patients with $ 1 psoriasis diagnosis and $ 1 psoriasis therapy prescription (ultraviolet light, systemic, or biologic) were classified to the treated or moderate to severe psoriasis (SP) cohort and all other patients with at least one psoriasis diagnosis were classified to the untreated or mild psoriasis (MP) cohort. The nonpsoriasis cohort (NP) was a random sample of patients from the database who did not have a psoriasis diagnosis. Efalizumab-treated patients were identified from the Raptiva Epidemiologic Study of Psoriasis Outcomes and Safety Events (RESPONSE). Safety outcomes defined as malignancy, nonmelanoma skin cancer, infections, psoriasis, inflammatory/autoimmune diseases, thrombocytopenia, and hepatic events were identified using emergency department or inpatient hospital codes in the health care database and using Medical Dictionary for Regulatory Activities (MedDRA) coding of serious adverse events in RESPONSE. Results: We identified 43,739 SP, 89,492 MP, and 2,227,968 NP patients in LabRx and 1206 efalizumab-treated patients in RESPONSE. Incidence rates of malignancies were 19.1 (95% CI, 18.0-20.3), 10.6 (10.0-11.3), and 11.1 (11.0-11.2) per 1000 person years in the SP, MP, and NP cohorts, respectively. The incidence rate of malignancies in efalizumab-treated patients was 17.7 (95% CI, 11.4-26.1) per 1000 person years. Incidence rates of infections were 40.0 (95% CI, 38.3-41.8), 20.9 (95% CI, 20.1-21.8), and 20.7 (95% CI, 20.6-20.9) per 1000 person years in the SP, MP, and NP cohorts, respectively. The incidence rate of infections in efalizumab-treated patients was 21.6 (95% CI, 14.6-32.0) per 1000 person years. Results for other safety events will be shown. Conclusions: The risk of selected safety events in the moderate to severe psoriasis cohort was higher than the mild psoriasis or nonpsoriasis cohorts of the health care database. Risk of these safety events in efalizumab-treated psoriasis patients appears to be within the range expected based on the moderate to severe psoriasis cohort.
Commercial support: 100% sponsored by Abbott. Commercial support: Sponsored by Genentech, Inc.
P3378 Adalimumab treatment for moderate psoriasis reduces the risk of transitioning to severe psoriasis Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; James Signorovitch, PhD, Analysis Group, Inc, Boston, MA, United States; Parvzez Mulani, PhD, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, PharmD, MPH, Abbott Laboratories, Abbott Park, IL, United States Objectives: Without appropriate treatment, patients (pts) with moderate psoriasis (Ps) can experience worsening symptoms and transition to severe Ps. The efficacy of adalimumab (ADA) in reducing Ps symptoms has been established for pts with moderate to severe Ps. The aims of this study were to determine the risk of transitioning to severe Ps among placebo-treated pts with moderate Ps, and to evaluate whether ADA treatment of pts with moderate Ps can prevent transition to severe Ps. Methods: Pts with moderate Ps (ie, 10 # PASI # 20 and Physician’s Global Assessment [PGA] of ‘‘moderate’’) at baseline were identified from two phase III, randomized, placebo-controlled trials (CHAMPION and REVEAL). During the trials’ initial 16-week double-blind treatment periods, PASI and PGA were evaluated at weeks 0, 1, 2, 4, 8, 12, and 16 or at early termination. A transition to severe Ps was defined as a follow-up visit with a PASI score [20 that had increased by $ 25% from baseline and PGA of ‘‘severe’’ or ‘‘very severe.’’ The cumulative incidence of pts transitioning to severe Ps was estimated using the KaplaneMeier (KM) method and compared for ADA versus placebo using a log-rank test. At week 16, pts who transitioned to severe Ps were compared to those who had not in terms of their Dermatology Life Quality Index (DLQI) and their Ps/psoriatic arthritis (PsA)-related pain.
P3380 A phase IV randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of efalizumab in patients with moderate to severe plaque psoriasis involving the scalp Leon Kircik, MD, Physicians Skin Care, Louisville, KY, United States; Ivor Caro, MD, Genentech, Inc, South San Francisco, CA, United States; Joel Schlessinger, MD, Skin Specialists, Omaha, Nebraska, United States; Yun Chen, PhD, Genentech, Inc, South San Francisco, CA, United States Introduction: This is a phase IV randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of subcutaneous (SC) efalizumab in adult patients ( $ 18 yrs of age) with chronic moderate to severe plaque psoriasis with involvement of the scalp who have had no previous exposure to efalizumab.
Conclusions: Placebo-treated pts with moderate Ps had a high 17-week risk of transitioning to severe Ps. Transitions to severe Ps were associated with significantly greater impairment of dermatologic quality of life and increased pain. The risk of transitioning from moderate to severe Ps was almost eliminated by ADA treatment.
Methods: The study consists of a screening period, a double-blind treatment period, an open-label treatment period, and an observation/follow-up period. The planned enrollment is 100 patients—67 in the efalizumab arm and 33 in the placebo arm. The patient’s plaque psoriasis must affect at least 30% of the scalp and the scalp psoriasis must have at least one of the following symptoms: erythema, desquamation, or induration. If the patient has psoriasis that involves only the scalp and nowhere else on the body, the patient may be eligible for the study if, in the investigator’s opinion, the plaque psoriasis is considered moderate to severe by Physician’s Global Assessment (PGA) and meets the minimum requirements. The primary objective is to evaluate the efficacy of a 12-week course of SC efalizumab compared with placebo in adults ( $ 18 yrs of age) with chronic moderate to severe plaque psoriasis involving the scalp, as measured by the proportion of patients achieving a $ 75% decrease of Psoriasis Scalp Severity Index (PSS) relative to day 0. Several secondary endpoints will also evaluate the efficacy of efalizumab. These will include PSSI-75 and PSSI-50; the proportion of patients achieving a PGA rating of clear (0), almost clear (1), or mild (2) at 12 and 24 weeks; Scalpdex, a quality of life instrument for scalp dermatoses; and an assessment of patient-reported scalp itch. Results: Currently, 121 patients have been screened and 83 patients have been enrolled in the study at 33 sites in the United States. Full enrollment is expected by August 2008. Conclusions: The results of this study will be the first from a placebo-controlled study that specifically addresses the efficacy of efalizumab on the treatment of scalp psoriasis. This presentation will include data from the first 12 weeks of the study.
Commercial support: 100% sponsored by Abbott.
Commercial support: Sponsored by Genentech, Inc.
Results: Among pts with moderate Ps at baseline (placebo, n ¼ 207; ADA, n ¼ 406), 21.3% (44/207) of placebo-treated pts and 2.2% (9/406) of ADA-treated pts transitioned to severe Ps, without adjusting for early dropout. By week 17, the KM-estimated risk of transitioning to severe Ps was 32.5% (95% CI, 20.0-49.8%) for placebo-treated pts and 2.3% (95% CI, 1.2-4.3%) for ADA-treated pts. The estimated hazard reduction of transitioning to severe Ps was 91.0% (95% CI, 81.3-95.5%) for ADA versus placebo. Compared with pts whose Ps remained moderate, pts who transitioned to severe Ps experienced, at week 16, more Ps/PsA-related pain by 39.9 (95% CI, 33.5-46.3) units on a scale of 0 to 100, and worse DLQI scores, by 9.4 units (95% CI, 7.9-10.8) on a scale of 0 to 30.
MARCH 2009
J AM ACAD DERMATOL
AB181