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Major adverse cardiovascular events among initiators of biologic therapies in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study
P8154
P8155
Major adverse cardiovascular events among initiators of biologic therapies in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study Robert Bissonnette, MD, Innovaderm Research, Inc, Montreal, Quebec, Canada; Alice B. Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; Kim Papp, MD, Probity Research, Waterloo, Ontario, Canada; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States
Malignancy events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study: Current status of observations David Fiorentino, MD, PhD, Stanford University, Redwood City, CA, United States; Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States; Vincent Ho, MD, University of British Columbia, Vancouver, British Columbia, Canada Objective: To report the accrual of malignancies excluding nonmelanoma skin cancers (NMSC) in the PSOLAR study.
Objective: To assess rates of major adverse cardiovascular (CV) events (MACE) among patients who initiated a new biologic therapy during the PSOLAR study. Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. Rates of MACE (CV death, nonfatal stroke, and nonfatal myocardial infarction) among initiators of biologics in PSOLAR are summarized. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR. A total of 57 MACE occurred across biologic treatment groups; of these 20 MACE were reported among patients who initiated a new biologic. The proportions of patients who initiated a new biologic and had a MACE at any time after starting treatment were: adalimumab (ADA) 10/1121 (0.89%, 95% CI 0.49%-1.63%), etanercept (ETA) 3/468 (0.64%, 95% CI 0.22%-1.87%), infliximab (IFX) 3/250 (1.20%, 95% CI 0.41%-3.47%) and ustekinumab (UST) 4/1576 (0.25%, 95% CI 0.10%0.65%). Of patients with a MACE, 3/1121 (0.27%, 95% CI 0.09%-0.78%) in the ADA group, 1/468 (0.21%, 95% CI 0.04%-1.2%) in the ETA group, 0/250 (0%) in the IFX group and 0/1576 (0%) in the UST group had their MACE within 91 days of starting treatment. Baseline demographics and features were generally similar across groups with some exceptions (eg, higher body mass index, and proportions of patients with psoriatic arthritis and CV disease for IFX patients). Onset of MACE after starting treatment ranged from 16-789 days for TNF-a inhibitor initiators and 204-814 days for UST initiators. Among the subsets of biona€ıve new users, 8/698 (1.15%, 95% CI 0.58%-2.25%) in the TNF-a inhibitor group and 0/352 (0%) in the UST group had a MACE after starting treatment. Of those in the biona€ıve TNF-a inhibitor new user group, 4 occurred within 91 days of starting treatment.
Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of malignancies excluding NMSC (ie, basal/squamous cell carcinomas) in PSOLAR overall and by exposure sub-groups is reported. Rates of malignancy are assessed using a definition of exposure based on whether patients had ever been exposed to a given therapy at any time before the event. In cases of exposure to multiple therapies, malignancies are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR (22,918 cumulative patient-years of follow-up). Unadjusted rates of malignancy, excluding NMSC, across treatment groups were: ustekinumab 0.36 events per 100 patient years of observation (PYO) [95% CI: 0.21, 0.56; 19/5332 PYO], infliximab/golimumab 0.70 per 100 PYO [95% CI: 0.44, 1.06; 22/3136], other biologics (almost exclusively etanercept/adalimumab) 0.58 per 100 PYO [95% CI: 0.44, 0.75; 59/10093], nonbiologic therapy 0.64 per 100 PYO [95% CI: 0.43, 0.93; 28/4357], and overall 0.56 per 100 PYO [95% CI: 0.47, 0.66; 128/22918]. Limitations: Due to channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments.
Conclusion: At this time, no distinct patterns of MACE have been observed after initiation of biologic therapies among PSOLAR patients. Additional analyses adjusting for demographic features, CV risk factors, and biologic exposure are planned.
Conclusions: Although many patients exposed to biologics have been exposed to multiple prior immunosuppressive therapies, rates of malignancy appear limited overall. Unadjusted rates show a trend towards lower rates in ustekinumab-treated patients, despite the rules of event attribution, compared to other treatment groups. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR is a powerful resource for tracking safety events of interest among patients eligible to receive systemic therapies.
Sponsored 100% by Janssen Research & Development, LLC.
Sponsored 100% by Janssen Research & Development, LLC.
Limitations: MACE among biologic initiators were limited in number and rates were not adjusted for differences among groups. CV events were confirmed by registry personnel but have not been externally adjudicated.
P8152 Major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study: Current status of observations Alice B. Gottlieb, MD, PhD, Tufts Medical Center, Boston, PA, United States; Francisco Kerdel, MD, University of Miami, Miami, FL, United States; Luigi Naldi, MD, Centro Studi GISED, Bergamo, Italy; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States Objective: To report the accrual of major adverse cardiovascular events (MACE) in the PSOLAR study. Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of MACE in PSOLAR overall and by exposure subgroups is reported. MACE are defined as cardiovascular death, nonfatal stroke, and confirmed nonfatal myocardial infarction. Rates of MACE are assessed using definitions of exposure based on treatment at any time or treatment within 91 days preceding the reported event. In cases of exposure to multiple therapies, MACE are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR (22,918 cumulative patient-years of follow-up). Unadjusted MACE rates, based on exposure at any time, were: ustekinumab 0.28 events per 100 years of patient observation (PYO) [95% CI: 0.16, 0.46; 15/5332 PYO]; infliximab/golimumab 0.32 per 100 PYO [95% CI: 0.15, 0.59; 10/3136 PYO]; other biologics (almost exclusively etanercept and adalimumab) 0.34 per 100 PYO [95% CI: 0.23, 0.47; 34/10093 PYO]; nonbiologic therapy 0.55 per 100 PYO [95% CI: 0.35, 0.82; 24/4357 PYO]; overall 0.36 per 100 PYO [95% CI: 0.29, 0.45; 83/22918 PYO]. Similar rates of MACE per 100 PYO were observed in the analysis of exposure based on treatment received within 91 days of an event. Limitations: Because of channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments. Conclusion: Although the numbers of MACE are limited, unadjusted MACE rates are generally similar across biologic treatment groups and trended higher in the no biologic group. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR represents a powerful resource for tracking safety events of interest, such as MACE, among patients receiving treatment for moderate to severe psoriasis. Sponsored 100% by Janssen Research & Development, LLC.
MAY 2014
P7770 Methotrexate plus prednisone: A cost-effective therapy avoided in dermatology Scott Davis, Wake Forest School of Medicine, Winston-Salem, NC, United States; Arash Taheri, MD, Wake Forest School of Medicine, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest School of Medicine, WinstonSalem, NC, United States Background: Methotrexate, used alone or in combination with prednisone, is a much less expensive alternative to costly biologics. The combination of methotrexate and prednisone is a common practice treatment of rheumatologic diseases but not in psoriasis. There are no data regarding safety of coadministration of these 2 drugs in psoriasis. Objective: To compare how frequently methotrexate plus prednisone is used in psoriasis, rheumatoid arthritis (RA), and psoriatic arthritis (PsA) visits. Methods: We used the National Ambulatory Medical Care Survey database to assess how often prednisone is used together with methotrexate in the US. Office visits with a prescription of methotrexate between 1993 and 2010 were identified, and rates of prednisone coprescription were determined for psoriasis, RA, and PsA visits. Results: Methotrexate was used in 40.1 million visits, including 19,410,000 RA visits, 1,460,000 psoriasis visits, and 1,600,000 PsA visits. Within these visits, prednisone was coprescribed at 8,060,000 RA visits (41.5%), as compared to 170,000 PsA visits (10.5%) and just 30,000 psoriasis visits (2.2%). Dermatologists coprescribed prednisone in methotrexate visits much less (6.4%) than rheumatologists (41.9%), internists, general and family practitioners, or other specialties. Limitations: Safety data on methotrexate/prednisone combination therapy were not recorded. Conclusion: Coprescription of methotrexate and prednisone is well accepted within the standard of care for RA but it is also used commonly in PsA. Because rebound flares of psoriasis are not commonly observed in these populations, adding prednisone to methotrexate should be tested to see if it might be a cost-effective alternative to biologics. The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P.
J AM ACAD DERMATOL
AB175
P8155
Major adverse cardiovascular events among initiators of biologic therapies in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study Robert Bissonnette, MD, Innovaderm Research, Inc, Montreal, Quebec, Canada; Alice B. Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; Kim Papp, MD, Probity Research, Waterloo, Ontario, Canada; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States
Malignancy events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study: Current status of observations David Fiorentino, MD, PhD, Stanford University, Redwood City, CA, United States; Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States; Vincent Ho, MD, University of British Columbia, Vancouver, British Columbia, Canada Objective: To report the accrual of malignancies excluding nonmelanoma skin cancers (NMSC) in the PSOLAR study.
Objective: To assess rates of major adverse cardiovascular (CV) events (MACE) among patients who initiated a new biologic therapy during the PSOLAR study. Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. Rates of MACE (CV death, nonfatal stroke, and nonfatal myocardial infarction) among initiators of biologics in PSOLAR are summarized. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR. A total of 57 MACE occurred across biologic treatment groups; of these 20 MACE were reported among patients who initiated a new biologic. The proportions of patients who initiated a new biologic and had a MACE at any time after starting treatment were: adalimumab (ADA) 10/1121 (0.89%, 95% CI 0.49%-1.63%), etanercept (ETA) 3/468 (0.64%, 95% CI 0.22%-1.87%), infliximab (IFX) 3/250 (1.20%, 95% CI 0.41%-3.47%) and ustekinumab (UST) 4/1576 (0.25%, 95% CI 0.10%0.65%). Of patients with a MACE, 3/1121 (0.27%, 95% CI 0.09%-0.78%) in the ADA group, 1/468 (0.21%, 95% CI 0.04%-1.2%) in the ETA group, 0/250 (0%) in the IFX group and 0/1576 (0%) in the UST group had their MACE within 91 days of starting treatment. Baseline demographics and features were generally similar across groups with some exceptions (eg, higher body mass index, and proportions of patients with psoriatic arthritis and CV disease for IFX patients). Onset of MACE after starting treatment ranged from 16-789 days for TNF-a inhibitor initiators and 204-814 days for UST initiators. Among the subsets of biona€ıve new users, 8/698 (1.15%, 95% CI 0.58%-2.25%) in the TNF-a inhibitor group and 0/352 (0%) in the UST group had a MACE after starting treatment. Of those in the biona€ıve TNF-a inhibitor new user group, 4 occurred within 91 days of starting treatment.
Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of malignancies excluding NMSC (ie, basal/squamous cell carcinomas) in PSOLAR overall and by exposure sub-groups is reported. Rates of malignancy are assessed using a definition of exposure based on whether patients had ever been exposed to a given therapy at any time before the event. In cases of exposure to multiple therapies, malignancies are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR (22,918 cumulative patient-years of follow-up). Unadjusted rates of malignancy, excluding NMSC, across treatment groups were: ustekinumab 0.36 events per 100 patient years of observation (PYO) [95% CI: 0.21, 0.56; 19/5332 PYO], infliximab/golimumab 0.70 per 100 PYO [95% CI: 0.44, 1.06; 22/3136], other biologics (almost exclusively etanercept/adalimumab) 0.58 per 100 PYO [95% CI: 0.44, 0.75; 59/10093], nonbiologic therapy 0.64 per 100 PYO [95% CI: 0.43, 0.93; 28/4357], and overall 0.56 per 100 PYO [95% CI: 0.47, 0.66; 128/22918]. Limitations: Due to channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments.
Conclusion: At this time, no distinct patterns of MACE have been observed after initiation of biologic therapies among PSOLAR patients. Additional analyses adjusting for demographic features, CV risk factors, and biologic exposure are planned.
Conclusions: Although many patients exposed to biologics have been exposed to multiple prior immunosuppressive therapies, rates of malignancy appear limited overall. Unadjusted rates show a trend towards lower rates in ustekinumab-treated patients, despite the rules of event attribution, compared to other treatment groups. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR is a powerful resource for tracking safety events of interest among patients eligible to receive systemic therapies.
Sponsored 100% by Janssen Research & Development, LLC.
Sponsored 100% by Janssen Research & Development, LLC.
Limitations: MACE among biologic initiators were limited in number and rates were not adjusted for differences among groups. CV events were confirmed by registry personnel but have not been externally adjudicated.
P8152 Major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study: Current status of observations Alice B. Gottlieb, MD, PhD, Tufts Medical Center, Boston, PA, United States; Francisco Kerdel, MD, University of Miami, Miami, FL, United States; Luigi Naldi, MD, Centro Studi GISED, Bergamo, Italy; Steve Fakharzadeh, MD, Janssen Services, LLC, Spring House, PA, United States Objective: To report the accrual of major adverse cardiovascular events (MACE) in the PSOLAR study. Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologics and/or conventional systemic agents. The accrual of MACE in PSOLAR overall and by exposure subgroups is reported. MACE are defined as cardiovascular death, nonfatal stroke, and confirmed nonfatal myocardial infarction. Rates of MACE are assessed using definitions of exposure based on treatment at any time or treatment within 91 days preceding the reported event. In cases of exposure to multiple therapies, MACE are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologics third, and nonbiologic therapy last. Results: As of the August 23, 2012 data cut, 11,900 of 12,000 patients had enrolled in PSOLAR (22,918 cumulative patient-years of follow-up). Unadjusted MACE rates, based on exposure at any time, were: ustekinumab 0.28 events per 100 years of patient observation (PYO) [95% CI: 0.16, 0.46; 15/5332 PYO]; infliximab/golimumab 0.32 per 100 PYO [95% CI: 0.15, 0.59; 10/3136 PYO]; other biologics (almost exclusively etanercept and adalimumab) 0.34 per 100 PYO [95% CI: 0.23, 0.47; 34/10093 PYO]; nonbiologic therapy 0.55 per 100 PYO [95% CI: 0.35, 0.82; 24/4357 PYO]; overall 0.36 per 100 PYO [95% CI: 0.29, 0.45; 83/22918 PYO]. Similar rates of MACE per 100 PYO were observed in the analysis of exposure based on treatment received within 91 days of an event. Limitations: Because of channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments. Conclusion: Although the numbers of MACE are limited, unadjusted MACE rates are generally similar across biologic treatment groups and trended higher in the no biologic group. These are preliminary results; PSOLAR will follow patients for up to 8 years, providing additional data over time. PSOLAR represents a powerful resource for tracking safety events of interest, such as MACE, among patients receiving treatment for moderate to severe psoriasis. Sponsored 100% by Janssen Research & Development, LLC.
MAY 2014
P7770 Methotrexate plus prednisone: A cost-effective therapy avoided in dermatology Scott Davis, Wake Forest School of Medicine, Winston-Salem, NC, United States; Arash Taheri, MD, Wake Forest School of Medicine, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest School of Medicine, WinstonSalem, NC, United States Background: Methotrexate, used alone or in combination with prednisone, is a much less expensive alternative to costly biologics. The combination of methotrexate and prednisone is a common practice treatment of rheumatologic diseases but not in psoriasis. There are no data regarding safety of coadministration of these 2 drugs in psoriasis. Objective: To compare how frequently methotrexate plus prednisone is used in psoriasis, rheumatoid arthritis (RA), and psoriatic arthritis (PsA) visits. Methods: We used the National Ambulatory Medical Care Survey database to assess how often prednisone is used together with methotrexate in the US. Office visits with a prescription of methotrexate between 1993 and 2010 were identified, and rates of prednisone coprescription were determined for psoriasis, RA, and PsA visits. Results: Methotrexate was used in 40.1 million visits, including 19,410,000 RA visits, 1,460,000 psoriasis visits, and 1,600,000 PsA visits. Within these visits, prednisone was coprescribed at 8,060,000 RA visits (41.5%), as compared to 170,000 PsA visits (10.5%) and just 30,000 psoriasis visits (2.2%). Dermatologists coprescribed prednisone in methotrexate visits much less (6.4%) than rheumatologists (41.9%), internists, general and family practitioners, or other specialties. Limitations: Safety data on methotrexate/prednisone combination therapy were not recorded. Conclusion: Coprescription of methotrexate and prednisone is well accepted within the standard of care for RA but it is also used commonly in PsA. Because rebound flares of psoriasis are not commonly observed in these populations, adding prednisone to methotrexate should be tested to see if it might be a cost-effective alternative to biologics. The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P.
J AM ACAD DERMATOL
AB175