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Long-term costs of biologics in the treatment of moderate to severe psoriasis in the United States
P6731
P6924
Lichen planus in a patient with chronic myeloid leukemia taking imatinib mesylate Carlos Gustavo Carneiro de Castro, MD, Policlınica Geral do Rio de Janeiro PGRJ, Rio de Janeiro, Brazil; Aline Sarkis dos Santos, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Carolina Degen Meotti, MD, Clınica privada, Rio de Janeiro, Brazil; Carolina Mendonc¸a Gama, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Luisa Kelmer Silveira, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Natalia Battisti Serafini, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Raquel Noschang Pereira, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil
Long-term safety of ustekinumab in patients with moderate to severe psoriasis through up to 5 years of continuous follow-up Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States
Background: Imatinib mesylate (MI) is a molecular inhibitor of tyrosine kinase that targets the fusion protein bcr-abl, c-kit and growth factors derived from platelets. It is used mainly for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Various skin reactions may occur with its use, often being dose-dependent. We present a patient with CML that after five months taking MI showed lesions consistent with lichen planus. In the recent years, rare cases of lichenoid dermatoses associated with the use of MI were reported. Case report: A 56-year-old man from Rio de Janeiro showed slightly pruritic lesions that initially affected the hands, with 2 months of evolution, starting after 5 months taking Gleevec (MI) 400 mg orally per day. The lesions were nonscaly violaceous plaques on the nasal dorsum, scaly violaceous plaques on the umbilicus, left supraclavicular region, palms extending to the wrists, dorsum of the right hand and more keratotic lesion on his left leg. In the oral cavity, the dorsum of the tongue had whitish diffuse lesions in a reticular pattern and a similar localized lesion on the hard palate. Also, cheilitis was observed. The possible diagnoses were lichen planus and lichenoid eruption induced by the use of MI. Histopathologic examination of the lesion on the palm showed hyperkeratosis, basal layer vacuolization, Civatte bodies, pigmentary incontinence and focal lichenoid infiltrate in the papillary dermis consistent with lichen planus. Until now the hematologic disease did not allow to reduce or suspend the medication. Topical corticosteroid improved only the slight pruritus and the cheilitis. Discussion: There are known different reaction to the MI, including maculopapular rash, toxic epidermal necrolysis, StevenseJohnson syndrome, acute generalized exanthematous pustulosis, Sweet syndrome, nodosum erythema, and porphyria cutanea tarda. Recently, though few in number, cases of lichenoid dermatoses with various patterns have been reported. This case was classified as lichen planus based on clinical presentation and histopathologic examination that did not show features typically found in lichenoid eruption (spongiosis, parakeratosis, exocytosis of lymphocytes, and eosinophilic infiltrate).
Objective: We report cumulative safety experience from the ustekinumab (UST) psoriasis clinical development program with up to 5 years of follow-up. Methods: Pooled safety across a phase II (n ¼ 320) and phase III [PHOENIX 1 (n ¼ 766), PHOENIX 2 (n ¼ 1230), ACCEPT (n ¼ 903)] clinical trials were analyzed. Pts received UST 45 mg or 90 mg sc 12 weekly.Overall AEs, serious AEs, infections and AEs leading to discontinuation were analyzed by year of follow-up (year 1 to year 5). AEs of interest (serious infections, malignancies, ajudicated-reported major adverse CV events [MACE]) were analyzed by UST dose group (45 mg or 90 mg) and by year of follow-up. Results expressed as rates per 100 pt-years of follow-up (PY) and 95% CI. Results: The analysis included 3117 pts (8998 PY); with 1482 (47.5%) pts treated continuously for [4yrs or more (including 838 [26.9%] for [5yrs). Rates of overall AEs and infections consistently decreased over time from years 1 to 5 while the rates of serious AEs and AEs leading to discontinuation were stable over time. Cumulative rates of serious infections per 100 PY for UST 45 mg and UST 90 mg groups were 0.98 (0.69, 1.35) and 1.19 (0.91, 1.52), respectively; rates for the dose groups combined from years 1 to 5 were 1.33, 1.03, 0.66, 1.11, and 1.17, respectively. Cumulative rates of nonmelanoma skin cancer (NMSC) per 100 PY for UST 45 mg and UST 90 mg groups were 0.64 (0.41, 0.95) and 0.44 (0.28, 0.66), respectively; rates for the dose groups combined from yr 1 to 5 were 0.94, 0.49, 0.40, 0.42, and 0.16, respectively. Cumulative rates of other malignancies per 100PY for UST45mg and UST 90mg groups were 0.59 (0.37, 0.89) and 0.61 (0.42, 0.87), respectively; rates for the dose groups combined from yr 1 to 5 were 0.39, 0.97, 0.40, 0.77, and 0.59, respectively. Ajudicated MACE rates per 100PY for UST 45mg and UST 90mg groups were 0.56 (0.35, 0.85) and 0.36 (0.22, 0.57), respectively; rates per 100PY (95%CI) by yr of follow-up in the combined UST groups were 0.47 (0.24, 0.82), 0.36 (0.13, 0.79), 0.46 (0.19, 0.96), 0.56 (0.24, 1.10), and 0.37 (0.15, 0.77) for yrs 1, 2, 3, 4, and 5, respectively. No TB, or serious hypersensitivity reactions were reported. Rates of serious infections, malignancies, and MACE were stable over time and were consistent with rates previously described and with observations in the general and/or psoriasis population. Conclusions:With continuous exposure for up to 5yrs and approximately 9000 PY exposure, the long-term safety profile of UST remained stable over time and consistent with report after 4yrs of follow-up. Commercial Support: Janssen Research and Development, LLC.
Commercial support: None identified.
P6675 Long-term costs of biologics in the treatment of moderate to severe psoriasis in the United States Sandrine Cure, MS, OptumInsight UK, Middlesex, United Kingdom; Frank Zhang, MD, MPH, Celgene Corporation, Warren, NJ, United States; Helene Cawston, MS, OptumInsight France, Nanterre, France; Steven R. Feldman, MD, PhD, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Thomas Tencer, PhD, Celgene Corporation, Warren, NJ, United States; Vidya Damera, MS, OptumInsight UK, Middlesex, United Kingdom Background: Biologic therapies have dramatically changed the management of moderate to severe psoriasis. The objective of the study was to estimate long-term costs of biologics in the treatment of moderate to severe psoriatic patients in the United States. Methods: We developed a 10-year Markov model describing the treatment pathway of patients with moderate to severe psoriasis eligible for biologics, using a monthly cycle length. Clinical efficacy data were obtained from published pivotal studies. Costs, resource usation and treatment pathways were obtained from literature and expert opinion. Patients transitioned through two lines of biologics (etanercept (ETA), infliximab (IFX), or adalimumab (ADA) in first line, ETA, IFX, ADA or ustekinumab in second line) followed by best supportive care (including combination therapies). Responders were defined as having a PASI 75 at the end of the trial period. Patients transitioned to the next line of therapy for non-response or discontinuation due to other causes (a 20% annual drop-out rate was assumed). Death from all causes was included. Direct costs included treatment acquisition and administration, monitoring, and hospitalizations. Productivity losses were based on length of hospitalization. Costs were discounted at a rate of 3% annually. A probabilistic sensitivity analysis was conducted to assess the possible implications of uncertainty around treatment efficacy, drop-out rates, and probability and cost of hospitalization. Results: For each first-line therapy, we averaged results across second-line therapies. The average time spent on the first biologic therapy was 2.2, 3.3, and 3.0 years for ETA, IFX, and ADA, respectively. From a third party payer’s perspective, the estimated 10-year cumulative direct costs per patient were $222,128 (95% CI: $220,963; $223,351) with ETA as first-line therapy, $216,804 (95% CI: $216,226; $218,585) with IFX, and $217,404 (95% CI: $215,640; $218,045) with ADA. Across scenarios, drug costs represented between 92.4% and 92.8% of total costs, monitoring costs between 4.0% and 4.4%, and hospitalization costs between 3.1% and 3.4%. The estimated productivity losses per patient were respectively $4195, $3580, and $3721 at 10 years with ETA, IFX, and ADA as first line therapy. Conclusion: Biologic therapies represent a significant cost burden to payers. Costs were similar independent of which biologic was used as first-line treatment. This study was sponsored by Celgene Corporation.
APRIL 2013
P6658 Major adverse cardiovascular events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Alice Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; L Naldi, MD, Centro Studi GISED, Bergamo, Italy; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; R Bissonnette, MD, Innovaderm Research, Inc, Montreal, Canada Objective: To report accrual rates of major adverse cardiovascular events (MACE) captured in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving/eligible to receive treatment with biologics and/or conventional systemic agents in academic/community practices. PSOLAR captures adverse events with recent or long-term prior exposure to systemic therapies. PSOLAR supports regulatory pharmacovigilance reporting for ustekinumab and infliximab. The accrual of MACE reported in the overall PSOLAR cohort and by exposure sub-groups through August 23, 2011 are summarized. MACE are defined as non-fatal cerebrovascular accident, confirmed non-fatal myocardial infarction, and cardiovascular death. Results: A total of 9, 495 patients had enrolled in PSOLAR (13, 733 cumulative patient-years). Differences in subgroup characteristics are noted (e.g., there are more patients over 65 years of age that have not been exposed to biologics, due to channeling of therapies). MACE rates were based on any prior exposure in order of attribution: ustekinumab 0.21 events per 100 years of patient observation (PYO) (95% CI: 0.07, 0.50, 5/2332 PYO); non-sponsor biologics (almost exclusively etanercept and adalimumab) 0.31 per 100 PYO (95% CI: 0.19, 0.48; 20/6458 PYO); non-biologic therapy 0.76 per 100 PYO (95% CI: 0.47, 1.15; 21/2784 PYO); overall 0.36 per 100 PYO (95% CI: 0.27, 0.48; 50/13733 PYO). The rate for infliximabeexposed patients was 0.22 per 100 PYO (95% CI: 0.08, 0.49, 6/2688 PYO; 2 pts with MACE were exposed to both infliximab and ustekinumab). Of ustekinumab patients, 57% were newly exposed at or after entry into PSOLAR, permitting assessment of events at the start of therapy. Formal, rigorous comparisons will require accrual of more events and statistical modeling to adjust for patient characteristics and risk factors. Conclusion: PSOLAR will follow patients for up to 8 years, providing more robust longitudinal results in the future. Although numbers of MACE events are small, large differences in MACE rates linked to ustekinumab or infliximab were not observed. PSOLAR represents a powerful resource for tracking safety events of interest among patients receiving treatment for moderate to severe psoriasis. Commercial Support: Janssen Services, LLC.
J AM ACAD DERMATOL
AB205
P6924
Lichen planus in a patient with chronic myeloid leukemia taking imatinib mesylate Carlos Gustavo Carneiro de Castro, MD, Policlınica Geral do Rio de Janeiro PGRJ, Rio de Janeiro, Brazil; Aline Sarkis dos Santos, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Carolina Degen Meotti, MD, Clınica privada, Rio de Janeiro, Brazil; Carolina Mendonc¸a Gama, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Luisa Kelmer Silveira, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Natalia Battisti Serafini, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil; Raquel Noschang Pereira, MD, Policlınica Geral do Rio de Janeiro - PGRJ, Rio de Janeiro, Brazil
Long-term safety of ustekinumab in patients with moderate to severe psoriasis through up to 5 years of continuous follow-up Kim Papp, MD, Probity Medical Research, Waterloo, Ontario, Canada; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States
Background: Imatinib mesylate (MI) is a molecular inhibitor of tyrosine kinase that targets the fusion protein bcr-abl, c-kit and growth factors derived from platelets. It is used mainly for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Various skin reactions may occur with its use, often being dose-dependent. We present a patient with CML that after five months taking MI showed lesions consistent with lichen planus. In the recent years, rare cases of lichenoid dermatoses associated with the use of MI were reported. Case report: A 56-year-old man from Rio de Janeiro showed slightly pruritic lesions that initially affected the hands, with 2 months of evolution, starting after 5 months taking Gleevec (MI) 400 mg orally per day. The lesions were nonscaly violaceous plaques on the nasal dorsum, scaly violaceous plaques on the umbilicus, left supraclavicular region, palms extending to the wrists, dorsum of the right hand and more keratotic lesion on his left leg. In the oral cavity, the dorsum of the tongue had whitish diffuse lesions in a reticular pattern and a similar localized lesion on the hard palate. Also, cheilitis was observed. The possible diagnoses were lichen planus and lichenoid eruption induced by the use of MI. Histopathologic examination of the lesion on the palm showed hyperkeratosis, basal layer vacuolization, Civatte bodies, pigmentary incontinence and focal lichenoid infiltrate in the papillary dermis consistent with lichen planus. Until now the hematologic disease did not allow to reduce or suspend the medication. Topical corticosteroid improved only the slight pruritus and the cheilitis. Discussion: There are known different reaction to the MI, including maculopapular rash, toxic epidermal necrolysis, StevenseJohnson syndrome, acute generalized exanthematous pustulosis, Sweet syndrome, nodosum erythema, and porphyria cutanea tarda. Recently, though few in number, cases of lichenoid dermatoses with various patterns have been reported. This case was classified as lichen planus based on clinical presentation and histopathologic examination that did not show features typically found in lichenoid eruption (spongiosis, parakeratosis, exocytosis of lymphocytes, and eosinophilic infiltrate).
Objective: We report cumulative safety experience from the ustekinumab (UST) psoriasis clinical development program with up to 5 years of follow-up. Methods: Pooled safety across a phase II (n ¼ 320) and phase III [PHOENIX 1 (n ¼ 766), PHOENIX 2 (n ¼ 1230), ACCEPT (n ¼ 903)] clinical trials were analyzed. Pts received UST 45 mg or 90 mg sc 12 weekly.Overall AEs, serious AEs, infections and AEs leading to discontinuation were analyzed by year of follow-up (year 1 to year 5). AEs of interest (serious infections, malignancies, ajudicated-reported major adverse CV events [MACE]) were analyzed by UST dose group (45 mg or 90 mg) and by year of follow-up. Results expressed as rates per 100 pt-years of follow-up (PY) and 95% CI. Results: The analysis included 3117 pts (8998 PY); with 1482 (47.5%) pts treated continuously for [4yrs or more (including 838 [26.9%] for [5yrs). Rates of overall AEs and infections consistently decreased over time from years 1 to 5 while the rates of serious AEs and AEs leading to discontinuation were stable over time. Cumulative rates of serious infections per 100 PY for UST 45 mg and UST 90 mg groups were 0.98 (0.69, 1.35) and 1.19 (0.91, 1.52), respectively; rates for the dose groups combined from years 1 to 5 were 1.33, 1.03, 0.66, 1.11, and 1.17, respectively. Cumulative rates of nonmelanoma skin cancer (NMSC) per 100 PY for UST 45 mg and UST 90 mg groups were 0.64 (0.41, 0.95) and 0.44 (0.28, 0.66), respectively; rates for the dose groups combined from yr 1 to 5 were 0.94, 0.49, 0.40, 0.42, and 0.16, respectively. Cumulative rates of other malignancies per 100PY for UST45mg and UST 90mg groups were 0.59 (0.37, 0.89) and 0.61 (0.42, 0.87), respectively; rates for the dose groups combined from yr 1 to 5 were 0.39, 0.97, 0.40, 0.77, and 0.59, respectively. Ajudicated MACE rates per 100PY for UST 45mg and UST 90mg groups were 0.56 (0.35, 0.85) and 0.36 (0.22, 0.57), respectively; rates per 100PY (95%CI) by yr of follow-up in the combined UST groups were 0.47 (0.24, 0.82), 0.36 (0.13, 0.79), 0.46 (0.19, 0.96), 0.56 (0.24, 1.10), and 0.37 (0.15, 0.77) for yrs 1, 2, 3, 4, and 5, respectively. No TB, or serious hypersensitivity reactions were reported. Rates of serious infections, malignancies, and MACE were stable over time and were consistent with rates previously described and with observations in the general and/or psoriasis population. Conclusions:With continuous exposure for up to 5yrs and approximately 9000 PY exposure, the long-term safety profile of UST remained stable over time and consistent with report after 4yrs of follow-up. Commercial Support: Janssen Research and Development, LLC.
Commercial support: None identified.
P6675 Long-term costs of biologics in the treatment of moderate to severe psoriasis in the United States Sandrine Cure, MS, OptumInsight UK, Middlesex, United Kingdom; Frank Zhang, MD, MPH, Celgene Corporation, Warren, NJ, United States; Helene Cawston, MS, OptumInsight France, Nanterre, France; Steven R. Feldman, MD, PhD, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Thomas Tencer, PhD, Celgene Corporation, Warren, NJ, United States; Vidya Damera, MS, OptumInsight UK, Middlesex, United Kingdom Background: Biologic therapies have dramatically changed the management of moderate to severe psoriasis. The objective of the study was to estimate long-term costs of biologics in the treatment of moderate to severe psoriatic patients in the United States. Methods: We developed a 10-year Markov model describing the treatment pathway of patients with moderate to severe psoriasis eligible for biologics, using a monthly cycle length. Clinical efficacy data were obtained from published pivotal studies. Costs, resource usation and treatment pathways were obtained from literature and expert opinion. Patients transitioned through two lines of biologics (etanercept (ETA), infliximab (IFX), or adalimumab (ADA) in first line, ETA, IFX, ADA or ustekinumab in second line) followed by best supportive care (including combination therapies). Responders were defined as having a PASI 75 at the end of the trial period. Patients transitioned to the next line of therapy for non-response or discontinuation due to other causes (a 20% annual drop-out rate was assumed). Death from all causes was included. Direct costs included treatment acquisition and administration, monitoring, and hospitalizations. Productivity losses were based on length of hospitalization. Costs were discounted at a rate of 3% annually. A probabilistic sensitivity analysis was conducted to assess the possible implications of uncertainty around treatment efficacy, drop-out rates, and probability and cost of hospitalization. Results: For each first-line therapy, we averaged results across second-line therapies. The average time spent on the first biologic therapy was 2.2, 3.3, and 3.0 years for ETA, IFX, and ADA, respectively. From a third party payer’s perspective, the estimated 10-year cumulative direct costs per patient were $222,128 (95% CI: $220,963; $223,351) with ETA as first-line therapy, $216,804 (95% CI: $216,226; $218,585) with IFX, and $217,404 (95% CI: $215,640; $218,045) with ADA. Across scenarios, drug costs represented between 92.4% and 92.8% of total costs, monitoring costs between 4.0% and 4.4%, and hospitalization costs between 3.1% and 3.4%. The estimated productivity losses per patient were respectively $4195, $3580, and $3721 at 10 years with ETA, IFX, and ADA as first line therapy. Conclusion: Biologic therapies represent a significant cost burden to payers. Costs were similar independent of which biologic was used as first-line treatment. This study was sponsored by Celgene Corporation.
APRIL 2013
P6658 Major adverse cardiovascular events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Alice Gottlieb, MD, PhD, Tufts Medical Center, Boston, MA, United States; L Naldi, MD, Centro Studi GISED, Bergamo, Italy; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; R Bissonnette, MD, Innovaderm Research, Inc, Montreal, Canada Objective: To report accrual rates of major adverse cardiovascular events (MACE) captured in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients receiving/eligible to receive treatment with biologics and/or conventional systemic agents in academic/community practices. PSOLAR captures adverse events with recent or long-term prior exposure to systemic therapies. PSOLAR supports regulatory pharmacovigilance reporting for ustekinumab and infliximab. The accrual of MACE reported in the overall PSOLAR cohort and by exposure sub-groups through August 23, 2011 are summarized. MACE are defined as non-fatal cerebrovascular accident, confirmed non-fatal myocardial infarction, and cardiovascular death. Results: A total of 9, 495 patients had enrolled in PSOLAR (13, 733 cumulative patient-years). Differences in subgroup characteristics are noted (e.g., there are more patients over 65 years of age that have not been exposed to biologics, due to channeling of therapies). MACE rates were based on any prior exposure in order of attribution: ustekinumab 0.21 events per 100 years of patient observation (PYO) (95% CI: 0.07, 0.50, 5/2332 PYO); non-sponsor biologics (almost exclusively etanercept and adalimumab) 0.31 per 100 PYO (95% CI: 0.19, 0.48; 20/6458 PYO); non-biologic therapy 0.76 per 100 PYO (95% CI: 0.47, 1.15; 21/2784 PYO); overall 0.36 per 100 PYO (95% CI: 0.27, 0.48; 50/13733 PYO). The rate for infliximabeexposed patients was 0.22 per 100 PYO (95% CI: 0.08, 0.49, 6/2688 PYO; 2 pts with MACE were exposed to both infliximab and ustekinumab). Of ustekinumab patients, 57% were newly exposed at or after entry into PSOLAR, permitting assessment of events at the start of therapy. Formal, rigorous comparisons will require accrual of more events and statistical modeling to adjust for patient characteristics and risk factors. Conclusion: PSOLAR will follow patients for up to 8 years, providing more robust longitudinal results in the future. Although numbers of MACE events are small, large differences in MACE rates linked to ustekinumab or infliximab were not observed. PSOLAR represents a powerful resource for tracking safety events of interest among patients receiving treatment for moderate to severe psoriasis. Commercial Support: Janssen Services, LLC.
J AM ACAD DERMATOL
AB205