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Malignancy events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations
P6558
P6037
Malignancies in the ustekinumab psoriasis clinical development program: Final report with up to 5 years of follow-up Kim Papp, MD, Probity Medical Research, Waterloo, Canada; Kenneth Gordon, MD, Northwestern University, Feinberg School of Medicine, Skokie, IL, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Vincent Ho, MD, University of British Columbia, Vancouver, Canada Objective: To report rates and types of malignancies observed in the ustekinumab (UST) psoriasis clinical development program with up to 5yrs of follow-up. Methods: Data were pooled across psoriasis trials [Phase2 trial (n ¼ 320), ACCEPT (n ¼ 903), PHOENIX1 (n ¼ 766), and PHOENIX2 (n ¼ 1230)] including 3117 USTtreated patients (8998 patient-years of follow-up[PY]). Patients with a prior history of malignancy were generally excluded from these studies. Rates (events/100PY, 95%CI) and types of nonmelanoma skin cancers (NMSCs, including basal [BCC] and squamous [SCC] cell carcinomas) and other malignancies were reported. For malignancies other than NMSC, standardized incidence ratios (SIRs) compared observed rates of malignancies in UST-treated patients to rates expected in the general US population from the NIH SEER database; adjusted for age, sex and race to control for some of the differences between the general and trial populations.
Metabolic syndrome in psoriasis: Unusual findings from a South Indian cohort Deepika Lunawat, MBBS, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India; Anandan Subramanian, MD, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
Results: Through year 5, cumulative rates of NMSCs per 100 PY (95% CI) for UST 45 mg, UST 90 mg, and combined UST groups were 0.64 (0.41, 0.95), 0.44 (0.28, 0.66), and 0.52 (0.39, 0.70), respectively. 47 patients reported NMSCs (40 BCC and 10 SCC [3 patients reported both BCC and SCC]), for a BCC to SCC ratio of 4:1. Rates of NMSC per 100 PY (95% CI) by year of follow-up for the combined UST group were 0.94 (0.61, 1.41), 0.49 (0.21, 0.96), 0.40 (0.15, 0.87), 0.42 (0.15, 0.91), and 0.16 (0.03, 0.47), respectively in years 1, 2, 3, 4, and 5. Cumulative rates of other malignancies per 100 PY (95% CI) for the UST 45 mg, UST 90 mg, and combined UST groups were 0.59 (0.37, 0.89), 0.61 (0.42, 0.87), and 0.60 (0.45, 0.78), respectively. 54 patients reported other malignancies; most commonly reported were prostate, melanoma, colorectal, and breast. Rates of other malignancies per 100 PY (95% CI) for the combined UST group by year of follow-up were 0.39 (0.19, 0.72), 0.97 (0.56, 1.58), 0.40 (0.15, 0.87), 0.77 (0.38, 1.37), and 0.59 (0.29, 1.05), respectively in years 1, 2, 3, 4, and 5. Rate of other malignancies reported in the combined UST group was comparable to that expected in the general US (SEER) population (SIR ¼ 0.98, 95% CI:0.74, 1.29). Conclusion: With up to 5 years of follow-up, rates of malignancies remained consistent with earlier analyses and no apparent dose effect was observed. Rates were generally stable over time, and the ratio of BCC:SCC was preserved. Observed rate of other malignancies was consistent with the expected rate in the general US population.
Background: Psoriasis, a chronic immune-mediated inflammatory disorder, has an estimated prevalence ranging between 0.6% and 4.8%. Several studies across different ethnicities have suggested a strong link between psoriasis and the individual components of metabolic syndrome. Objective: To investigate the prevalence of metabolic syndrome in South Indian patients accessing the psoriasis clinic of a tertiary care center and to evaluate specific disease characteristics for risk of metabolic syndrome. Methods: Adult patients registered at an outpatient psoriasis clinic at a tertiary care center in South India, were assessed on the following variables: age, gender, psoriasis type, height, weight, obesity, blood pressure, blood glucose, blood lipids, presence of cardiovascular disease, cerebrovascular accident, smoking, alcohol, tobacco consumption, physical activity, menopause, family history of psoriasis, age of disease onset, disease duration, nail and scalp involvement, arthropathy and metabolic syndrome, over a 1-year study period. Metabolic syndrome was diagnosed using the National Cholesterol Education Program Adult Treatment Panel III criteria. Statistical analysis of the data was done using SPSS 15. Results: A total of 141 patients (63 males, 44.7%) were enrolled with a median age of 48 years. Of these, 44% had systemic arterial hypertension, 51.8% had impaired fasting plasma glucose levels, 61% had low HDL levels, 39% had hypertriglyceridemia and 42.6% were obese. Nearly half, 45.4%, had metabolic syndrome. Psoriasis patients with metabolic syndrome (50.59yrs) were found to be significantly older than those without metabolic syndrome (42.90yrs) (P \.001). Scalp involvement in psoriasis was found to be significantly associated with metabolic syndrome (P ¼ .003). Males were found to have more severe psoriasis than females. No correlation was found between metabolic syndrome and psoriasis disease duration or with type of psoriasis. Conclusion: Our study found an unusually high prevalence of metabolic syndrome, dyslipidemia and impaired glucose metabolism, in patients with psoriasis, compared to national and international data from most previous studies. The strong correlation between scalp involvement and metabolic syndrome has never been reported so far. We report these findings, to highlight the need for screening for metabolic syndrome in all cases of psoriasis, to help prevent morbidity and improve patients’ quality of life. Commercial support: None identified.
Supported by Janssen Services, LLC.
P6448 Malignancy events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Bruce Strober, MD, University of Connecticut School of Medicine, Farmington, CT, United States; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; Mark Lebwohl, MD, Mount Sinai Medical Center, New York, NY, United States Objective: To report malignancy events observed in PSOLAR, a multicenter, longitudinal, observational study. Methods: PSOLAR captures events following exposure to systemic therapies. Safety observations captured for ustekinumab- and infliximab-exposed pts support sponsor regulatory commitments. Prevalence and incidence of malignancy in moderate to severe psoriasis populations using systemic immunomodulatory therapies are being evaluated. Accrual of malignancies by exposure subgroups through August 23, 2011 are summarized. Malignancies reported here are inclusive of all types except non-melanoma skin cancer (NMSC, ie, basal/squamous cell carcinomas). Results: 9495 pts enrolled in PSOLAR (13, 733 cumulative pt-years). Unadjusted rates of malignancy excluding NMSC, were generally similar across groups as follows (in order of attribution): ustekinumab 0.60 events/100 pt years of observation (PYO) [14 events/2332 PYO], anti-TNF sponsor biologics (infliximab and golimumab) 0.65/100 PYO [14/2158], nonsponsor biologics (almost exclusively etanercept/adalimumab) 0.60/100 PYO [39/6458], nonbiologic therapy 0.61/100 PYO [17/2784], and overall 0.61/100 PYO [84/13733]. (Exposure definition: event counts add to exposure group with highest position in the order of attribution, before/at the time of AE.) 57% of ustekinumab pts were exposed at/after entry into PSOLAR; ustekinumab cohort represents a balance of new and prior/ongoing exposure to sample event rates at varying levels of exposure. To better compare rates observed in pts with different exposure patterns, more malignancy events than currently available are needed to undertake rigorous, comparative statistical analyses. Limitations: Because of channeling of therapy, differences in subgroup characteristics (eg, more pts aged [65 yrs not exposed to biologics exist, which could influence malignancy rate, given long latency of cancer events and prevalence in the elderly). Any formal comparison will require statistical modeling to better adjust for pt characteristics and risks, including consideration of multiple treatments. Conclusion: These are preliminary observations and PSOLAR will follow pts for up to 8yrs, providing more robust results. Although the numbers of malignancy events are small, initial rates are generally similar to those in registrational programs with ustekinumab/infliximab. PSOLAR is a powerful resource for tracking safety events of interest among pts eligible to receive systemic therapies. Supported by Janssen Services, LLC.
AB206
J AM ACAD DERMATOL
P6378 Palmoplantar hyperkeratotic psoriasis with a combination of adalimumab and alitretinoin: Clinical and histologic finding Nevena Skroza, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy; Claudio Di Cristofano, MD, PhD, Department of Medical-Surgical Sciences and Biotechnologies Experimental Medicine University of Rome ‘‘Sapienza,’’ Polo Pontino, Italy; Concetta Potenza, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy; Ilaria Proietti, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy Background: Palm and sole psoriasis occours approximately in 15% of patients. Occupational manual workers are especially at risk and the isomorphic Koebner reaction may actually contribute to significant palmar hyperkeratosis even refractory to biologics. Oral alitretinoin (9-cis retinoic acid), which has been emerging as novel treatment for recalcitrant chronic hand eczema, is a vitamin A derivative with immunomodulatory and antiinflammatory activities. The specific alitretinoin mechanism of action which finally leads to skin inflammatory changes improvement is still far from being understood. We evaluated the therapeutic effect of alitretinoin plus adalimumab in patients with recalcitrant palmoplantar psoriasis thus investigating subsequent immunopathological alterations. Methods: Fifteen patients with palmoplantar psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks plus adalimumab 40 mg once every 2 weeks. Efficacy was assessed by PASI, Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus along with an overall patient assessment. Immunostaining for TNFa, p40 IL12-23, RAR, and RXR was performed from skin lesions biopsied before and after 12 weeks of treatment. Results: PASI, PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with adalimumab plus alitretinoin. The overall patient assessment ranged from 60 to 90% clinical improvement. A significant reduction of TNFa, p40 IL12-23, RAR and RXR at immunohistochemistry was also observed reflecting clinical improvement. Discussion: Our findings suggest how alitretinoin may be used effectively in combination with adalimumab in patients with refractory palmoplantar hyperkeratotic psoriasis. Future randomized trials are required to confirm the safety and efficacy of such therapeutic option. Commercial support: None identified.
APRIL 2013
P6037
Malignancies in the ustekinumab psoriasis clinical development program: Final report with up to 5 years of follow-up Kim Papp, MD, Probity Medical Research, Waterloo, Canada; Kenneth Gordon, MD, Northwestern University, Feinberg School of Medicine, Skokie, IL, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Vincent Ho, MD, University of British Columbia, Vancouver, Canada Objective: To report rates and types of malignancies observed in the ustekinumab (UST) psoriasis clinical development program with up to 5yrs of follow-up. Methods: Data were pooled across psoriasis trials [Phase2 trial (n ¼ 320), ACCEPT (n ¼ 903), PHOENIX1 (n ¼ 766), and PHOENIX2 (n ¼ 1230)] including 3117 USTtreated patients (8998 patient-years of follow-up[PY]). Patients with a prior history of malignancy were generally excluded from these studies. Rates (events/100PY, 95%CI) and types of nonmelanoma skin cancers (NMSCs, including basal [BCC] and squamous [SCC] cell carcinomas) and other malignancies were reported. For malignancies other than NMSC, standardized incidence ratios (SIRs) compared observed rates of malignancies in UST-treated patients to rates expected in the general US population from the NIH SEER database; adjusted for age, sex and race to control for some of the differences between the general and trial populations.
Metabolic syndrome in psoriasis: Unusual findings from a South Indian cohort Deepika Lunawat, MBBS, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India; Anandan Subramanian, MD, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
Results: Through year 5, cumulative rates of NMSCs per 100 PY (95% CI) for UST 45 mg, UST 90 mg, and combined UST groups were 0.64 (0.41, 0.95), 0.44 (0.28, 0.66), and 0.52 (0.39, 0.70), respectively. 47 patients reported NMSCs (40 BCC and 10 SCC [3 patients reported both BCC and SCC]), for a BCC to SCC ratio of 4:1. Rates of NMSC per 100 PY (95% CI) by year of follow-up for the combined UST group were 0.94 (0.61, 1.41), 0.49 (0.21, 0.96), 0.40 (0.15, 0.87), 0.42 (0.15, 0.91), and 0.16 (0.03, 0.47), respectively in years 1, 2, 3, 4, and 5. Cumulative rates of other malignancies per 100 PY (95% CI) for the UST 45 mg, UST 90 mg, and combined UST groups were 0.59 (0.37, 0.89), 0.61 (0.42, 0.87), and 0.60 (0.45, 0.78), respectively. 54 patients reported other malignancies; most commonly reported were prostate, melanoma, colorectal, and breast. Rates of other malignancies per 100 PY (95% CI) for the combined UST group by year of follow-up were 0.39 (0.19, 0.72), 0.97 (0.56, 1.58), 0.40 (0.15, 0.87), 0.77 (0.38, 1.37), and 0.59 (0.29, 1.05), respectively in years 1, 2, 3, 4, and 5. Rate of other malignancies reported in the combined UST group was comparable to that expected in the general US (SEER) population (SIR ¼ 0.98, 95% CI:0.74, 1.29). Conclusion: With up to 5 years of follow-up, rates of malignancies remained consistent with earlier analyses and no apparent dose effect was observed. Rates were generally stable over time, and the ratio of BCC:SCC was preserved. Observed rate of other malignancies was consistent with the expected rate in the general US population.
Background: Psoriasis, a chronic immune-mediated inflammatory disorder, has an estimated prevalence ranging between 0.6% and 4.8%. Several studies across different ethnicities have suggested a strong link between psoriasis and the individual components of metabolic syndrome. Objective: To investigate the prevalence of metabolic syndrome in South Indian patients accessing the psoriasis clinic of a tertiary care center and to evaluate specific disease characteristics for risk of metabolic syndrome. Methods: Adult patients registered at an outpatient psoriasis clinic at a tertiary care center in South India, were assessed on the following variables: age, gender, psoriasis type, height, weight, obesity, blood pressure, blood glucose, blood lipids, presence of cardiovascular disease, cerebrovascular accident, smoking, alcohol, tobacco consumption, physical activity, menopause, family history of psoriasis, age of disease onset, disease duration, nail and scalp involvement, arthropathy and metabolic syndrome, over a 1-year study period. Metabolic syndrome was diagnosed using the National Cholesterol Education Program Adult Treatment Panel III criteria. Statistical analysis of the data was done using SPSS 15. Results: A total of 141 patients (63 males, 44.7%) were enrolled with a median age of 48 years. Of these, 44% had systemic arterial hypertension, 51.8% had impaired fasting plasma glucose levels, 61% had low HDL levels, 39% had hypertriglyceridemia and 42.6% were obese. Nearly half, 45.4%, had metabolic syndrome. Psoriasis patients with metabolic syndrome (50.59yrs) were found to be significantly older than those without metabolic syndrome (42.90yrs) (P \.001). Scalp involvement in psoriasis was found to be significantly associated with metabolic syndrome (P ¼ .003). Males were found to have more severe psoriasis than females. No correlation was found between metabolic syndrome and psoriasis disease duration or with type of psoriasis. Conclusion: Our study found an unusually high prevalence of metabolic syndrome, dyslipidemia and impaired glucose metabolism, in patients with psoriasis, compared to national and international data from most previous studies. The strong correlation between scalp involvement and metabolic syndrome has never been reported so far. We report these findings, to highlight the need for screening for metabolic syndrome in all cases of psoriasis, to help prevent morbidity and improve patients’ quality of life. Commercial support: None identified.
Supported by Janssen Services, LLC.
P6448 Malignancy events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Bruce Strober, MD, University of Connecticut School of Medicine, Farmington, CT, United States; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; Mark Lebwohl, MD, Mount Sinai Medical Center, New York, NY, United States Objective: To report malignancy events observed in PSOLAR, a multicenter, longitudinal, observational study. Methods: PSOLAR captures events following exposure to systemic therapies. Safety observations captured for ustekinumab- and infliximab-exposed pts support sponsor regulatory commitments. Prevalence and incidence of malignancy in moderate to severe psoriasis populations using systemic immunomodulatory therapies are being evaluated. Accrual of malignancies by exposure subgroups through August 23, 2011 are summarized. Malignancies reported here are inclusive of all types except non-melanoma skin cancer (NMSC, ie, basal/squamous cell carcinomas). Results: 9495 pts enrolled in PSOLAR (13, 733 cumulative pt-years). Unadjusted rates of malignancy excluding NMSC, were generally similar across groups as follows (in order of attribution): ustekinumab 0.60 events/100 pt years of observation (PYO) [14 events/2332 PYO], anti-TNF sponsor biologics (infliximab and golimumab) 0.65/100 PYO [14/2158], nonsponsor biologics (almost exclusively etanercept/adalimumab) 0.60/100 PYO [39/6458], nonbiologic therapy 0.61/100 PYO [17/2784], and overall 0.61/100 PYO [84/13733]. (Exposure definition: event counts add to exposure group with highest position in the order of attribution, before/at the time of AE.) 57% of ustekinumab pts were exposed at/after entry into PSOLAR; ustekinumab cohort represents a balance of new and prior/ongoing exposure to sample event rates at varying levels of exposure. To better compare rates observed in pts with different exposure patterns, more malignancy events than currently available are needed to undertake rigorous, comparative statistical analyses. Limitations: Because of channeling of therapy, differences in subgroup characteristics (eg, more pts aged [65 yrs not exposed to biologics exist, which could influence malignancy rate, given long latency of cancer events and prevalence in the elderly). Any formal comparison will require statistical modeling to better adjust for pt characteristics and risks, including consideration of multiple treatments. Conclusion: These are preliminary observations and PSOLAR will follow pts for up to 8yrs, providing more robust results. Although the numbers of malignancy events are small, initial rates are generally similar to those in registrational programs with ustekinumab/infliximab. PSOLAR is a powerful resource for tracking safety events of interest among pts eligible to receive systemic therapies. Supported by Janssen Services, LLC.
AB206
J AM ACAD DERMATOL
P6378 Palmoplantar hyperkeratotic psoriasis with a combination of adalimumab and alitretinoin: Clinical and histologic finding Nevena Skroza, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy; Claudio Di Cristofano, MD, PhD, Department of Medical-Surgical Sciences and Biotechnologies Experimental Medicine University of Rome ‘‘Sapienza,’’ Polo Pontino, Italy; Concetta Potenza, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy; Ilaria Proietti, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino, Italy Background: Palm and sole psoriasis occours approximately in 15% of patients. Occupational manual workers are especially at risk and the isomorphic Koebner reaction may actually contribute to significant palmar hyperkeratosis even refractory to biologics. Oral alitretinoin (9-cis retinoic acid), which has been emerging as novel treatment for recalcitrant chronic hand eczema, is a vitamin A derivative with immunomodulatory and antiinflammatory activities. The specific alitretinoin mechanism of action which finally leads to skin inflammatory changes improvement is still far from being understood. We evaluated the therapeutic effect of alitretinoin plus adalimumab in patients with recalcitrant palmoplantar psoriasis thus investigating subsequent immunopathological alterations. Methods: Fifteen patients with palmoplantar psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks plus adalimumab 40 mg once every 2 weeks. Efficacy was assessed by PASI, Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus along with an overall patient assessment. Immunostaining for TNFa, p40 IL12-23, RAR, and RXR was performed from skin lesions biopsied before and after 12 weeks of treatment. Results: PASI, PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with adalimumab plus alitretinoin. The overall patient assessment ranged from 60 to 90% clinical improvement. A significant reduction of TNFa, p40 IL12-23, RAR and RXR at immunohistochemistry was also observed reflecting clinical improvement. Discussion: Our findings suggest how alitretinoin may be used effectively in combination with adalimumab in patients with refractory palmoplantar hyperkeratotic psoriasis. Future randomized trials are required to confirm the safety and efficacy of such therapeutic option. Commercial support: None identified.
APRIL 2013