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Long-term safety of adalimumab for psoriasis: An analysis of all adalimumab exposure in all global clinical trials
P3335
P3337
Combination regimen of acitretin and adalimumab for moderate to severe psoriasis WeiWei Dai, DO, Arlington Center for Dermatology, Arlington, TX, United States; Angela Yen Moore, MD, Arlington Center for Dermatology, Arlington, TX, United States
Long-term safety of adalimumab for psoriasis: An analysis of all adalimumab exposure in all global clinical trials Craig Leonardi, Department of Dermatology, Saint Louis University, Saint Louis, MO, United States; Kim Papp, Probity Medical Research, Waterloo, ON, Canada; Stephen Rozzo, Abbott, Abbott Park, IL, United States; Yihua Gu, Abbott, Abbott Park, IL, United States
Background: Monotherapy with a biologic or traditional systemic agent is often used to treat moderate to severe psoriasis. However, remission can be difficult to achieve and maintain in this patient population. Long-term use of a single systemic agent may result in loss of efficacy, adverse effects, and cumulative toxicities. Combination therapy with two systemic agents with alternate mechanisms of action may provide a synergistic therapeutic enhancement without a significant increase in adverse effects. Objective: To assess the therapeutic efficacy and adverse effect profile of the combination regimen acitretin and adalimumab for the treatment of moderate to severe psoriasis. Method: Retrospective analysis of 21 patients with moderate to severe psoriasis treated with a combination regimen of acitretin and adalimumab between January 2004 and June 2009. Of these 21 patients, 18 had plaque psoriasis, and three had palmoplantar psoriasis. All patients demonstrated an inadequate response to systemic monotherapies including acitretin (29%) and biological agents (71%) before this study. Patients were then started on a combination therapy of adalimumab 40mg every other week and acitretin 10 or 25 mg daily. Severity of the psoriasis was assessed by the percent of body surface affected (BSA). A change in BSA from baseline was used to assess the efficacy of this treatment. Moderate improvement was defined as [50% decrease in BSA and marked improvement was defined as [75% decrease. Presence of psoriatic arthritis was noted. All adverse events were reported in this study. Results: Of the 21 patients with moderate to severe psoriasis, the mean (6 SE) BSA before treatment initiation was 30% 6 5.8. Compared to this baseline, follow-up at 8 weeks, 14 weeks, and 20 weeks demonstrated a mean (6 SE) BSA of 24% 6 6.1 (P ¼ .003), 15% 6 5.2 (P ¼ .012), and 13% 6 6.0 (P ¼ .017), respectively. Percentage of patients with moderate improvement was 33% at 8 weeks, 65% at 14 weeks, and 64% at 20 weeks. Percentage of patients with marked improvement was 5% at 8 weeks, 18% at 14 weeks, and 21% at 20 weeks. Patients with palmoplantar psoriasis exhibited functional improvement in their daily activities at a mean of 4 weeks. Psoriatic arthritis was present in 19 patients; of these, 79% reported clinical resolution of joint symptoms during treatment. The combination regimen was well tolerated. Adverse effects include generalized pruritis (1/21), dry skin (1/21), sticky skin (1/21), upper respiratory tract infection (2/21), and cellulitis (2/21). All laboratory abnormalities were mild and did not warrant discontinuation of treatment.
Objective: To assess the long-term safety data for all patients treated with adalimumab in all phase II, II/III, III and IIIb clinical trials of moderate to severe psoriasis. Methods: Safety data from all patients receiving $ 1 dose of adalimumab in 11 clinical trials (7 RCTs and 4 extension trials) of adalimumab in moderate to severe psoriasis were included in this analysis. Two overlapping safety datasets were created by pooling all data collected from clinical trials through April 15, 2007 and through November 6, 2008, respectively. Most patients received adalimumab subcutaneously at a dosage of 40 mg every other week, begun either 1 week after an initial dose of 80mg, or after a period of treatment with placebo. Adverse events (AE) were counted if they occurred up to 70 days after discontinuation of adalimumab. The definition of ‘‘allergic reactions’’ was expanded for the November 6, 2008 dataset to include ‘‘urticaria’’ and other terms. Standardized Incidence Ratios (SIRs) were determined using the SEER data base for comparison. Results: The 2007 and 2008 datasets included 1819 and 2197 patients, respectively, with total exposures of 2424.7 and 4351.9 patient-years (PYs). Overall AE rates (as events per PY) for the 2007 and 2008 data sets were 2.975 and 2.757, and serious AE rates were 0.065 and 0.072, respectively. Rates of other types of AEs for the 2007 and 2008 data sets, respectively, were: infections, 0.839 and 0.802; serious infections, 0.013 and 0.014; opportunistic infections, 0.002 and 0.003; nonmelanoma skin cancer (NMSC), 0.008 and 0.007; demyelinating disorders, 0.000 and \0.001; congestive heart failure, \0.001 and 0.002; tuberculosis, 0.002 and \0.001; allergic reactions, 0.002 and 0.009; and malignancies (excluding NMSC), 0.005 and 0.006. SIR (95% CI) for malignancies (excluding NMSC) were 0.80 (0.41-1.39) and 0.89 (0.57-1.32), respectively, for 2007 and 2008. Rates were \0.001 for lupus-like syndrome in both data sets. No lymphomas were observed. Conclusions: AE rates from pooled results for all clinical trials of adalimumab in psoriasis were low and generally stable over time. Commercial support: Abbott sponsored the study and the poster.
Conclusions: In this series of patients, acitretin and adalimumab combination regimen shows efficacy without significant increase in adverse events in the treatment of moderate to severe psoriasis refractory to systemic monotherapy. Further clinical studies need to be conducted to address the efficacy and safety of this combination regimen. Commercial support: None identified.
P3336 The ustekinumab safety experience in patients with moderate to severe psoriasis: Results from pooled analyses of phase II and phase III clinical trial data Kenneth Gordon, MD, NorthShore University Health Systems, Skokie, IL, United States; Craig Leonardi, MD, Central Dermatology, Saint Louis, MO, United States; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; Newman Yeilding, MD, Centocor Research and Development, Inc, Malvern, PA, United States Aim: To analyze the cumulative safety experience of ustekinumab, a novel human monoclonal antibody against interleukin 12/23p40, across phase II and III psoriasis clinical trials through 18 months of treatment. Methods: Safety data were pooled from all phase II and III double-blind, placebocontrolled studies, including one phase II study (n ¼ 320 patients with up to 36 weeks safety experience), and two phase III studies: PHOENIX 1 (n ¼ 766 patients with up to 76 weeks safety experience) and PHOENIX 2 (n ¼ 1230 patients with up to 52 weeks safety experience). Ustekinumab 45mg and 90mg dosing were studied in each trial (phase II: 1 injection or 4 weekly injections; phase III: injections at week 0, 4, and every 12 weeks thereafter). Placebo-treated patients crossed over to ustekinumab at week 20 (phase II) or week 12 (phase III). Results: Across the phase II and III trials, a total of 2266 patients were exposed to ustekinumab, of whom 1970 patients were exposed for $ 6 months, 1285 exposed for $ 12 months, and 373 for $ 18 months. During the common 12-week controlled period of the trials, 50.4%,57.6%,and 51.6% of patients treated with placebo, 45-mg dosing, and 90-mg dosing, respectively, experienced $ 1 adverse event (AE). In these respective groups, 1.4%, 1.6%, and 1.4% experienced $ 1 serious AE (SAE); 23.2%, 27.0%, and 24.1% experienced $ 1 infection; and 1.9%, 1.1%, and 1.4% experienced an AE leading to treatment discontinuation Cumulative rates of AEs, SAEs, infections, and AEs leading to study agent discontinuation during the controlled and uncontrolled periods did not increase over time with increased duration of exposure or with increased cumulative exposure. Noncutaneous malignancies in the controlled period occurred at 0.25 per 100 PY for ustekinumab-treated patients compared to 0.57 per 100 PY for placebo-treated patients. The incidence of noncutaneous malignancies during the controlled and uncontrolled periods was 0.36 per 100 PY for ustekinumab-treated patients. Conclusion: Ustekinumab was well tolerated with a favorable safety profile which remained consistent over time with up to approximately 18 months of treatment. Commercial support: Centocor Research and Development.
AB132
J AM ACAD DERMATOL
P3338 Twice-weekly use of clobetasol propionate 0.05% shampoo is effective and safe for the long-term control of scalp psoriasis Yves Poulin, MD, Centre de Recherche Dermatologique du Quebec Me´tropolitain, Quebec City, Quebec, Canada; Kim Papp, K. Papp Clinical Research, Waterloo, Canada; Lyn Guenther, MD, MHS, The Guenther Dermatolgy Research Centre, London, Ontario, Canada; Robert Bissonnette, MD, Innovaderm Research Laval, Laval, Quebec, Canada An unmet need of scalp psoriasis treatment is the long-term maintenance of remission. A short-contact shampoo formulation of 0.05% clobetasol propionate, a super-potent corticosteroid was developed to optimize efficacy and reduce potential adverse effects. A study was conducted to assess the efficacy and safety profile of twice weekly use of this 0.05% clobetasol propionate (CP) shampoo formulation as maintenance treatment for scalp psoriasis. Patients aged 18 years or older, with moderate to severe scalp psoriasis, defined by a Global Severity Score (GSS) of 3 or 4 (on a 0 to 5 scale), first entered an initial phase where they applied CP shampoo once daily for up to 4 weeks. Patients showing a GSS # 2 then entered a doubleblind maintenance phase in which they were randomized to either CP shampoo or its vehicle, to be used twice weekly for up to 6 months. If relapse occurred (GSS[2), patients of both groups went back to a 4-week daily treatment with CP shampoo after which they re-entered in double-blind to the twice weekly maintenance regimen if the GSS was # 2. Patients with a GSS [ 2 at two consecutive visits were withdrawn from the study. The primary efficacy measure was the time to first relapse. Safety was evaluated throughout the trial by assessment of burning, skin atrophy and telangiectasia, and retrieval of adverse events. A morning serum cortisol dosage was done at the last visit. Out of the 288 enrolled in the initial phase, 217 patients (75%) entered the maintenance phase. Mean age was 50.4 years (range, 1882). Mean GSS at maintenance baseline was 1.5 in both groups. The median time to first relapse was 58 days with CP shampoo versus 29 days with the vehicle (P \ .0001), and mean time to first relapse was 93.7 days (6 6.6) with CP shampoo versus 55 days (64.8) with the vehicle (P \.0001). During the twice weekly maintenance regimen, 44.3% patients had no relapse with CP shampoo versus 15.5% with the vehicle after 3 months, and 31.1% and 8.1% patients, respectively (P \.001), after 6 months. During the entire study (initial phase and maintenance phase), the mean number of days of applications of CP shampoo was 80.5 in the CP shampoo arm and 60.3 in the vehicle arm. CP shampoo appeared to be safe. The vast majority of patients had no burning sensation. No skin atrophy, telangiectasia, or significant decrease of serum cortisol levels was observed. Adverse event rate was comparable in both treatment groups. Twice-weekly use of clobetasol propionate 0.05% shampoo is effective and safe for long-term maintenance treatment of scalp psoriasis. Commercial support: Study and poster support provided by Galderma Laboratories, L.P.
MARCH 2010
P3337
Combination regimen of acitretin and adalimumab for moderate to severe psoriasis WeiWei Dai, DO, Arlington Center for Dermatology, Arlington, TX, United States; Angela Yen Moore, MD, Arlington Center for Dermatology, Arlington, TX, United States
Long-term safety of adalimumab for psoriasis: An analysis of all adalimumab exposure in all global clinical trials Craig Leonardi, Department of Dermatology, Saint Louis University, Saint Louis, MO, United States; Kim Papp, Probity Medical Research, Waterloo, ON, Canada; Stephen Rozzo, Abbott, Abbott Park, IL, United States; Yihua Gu, Abbott, Abbott Park, IL, United States
Background: Monotherapy with a biologic or traditional systemic agent is often used to treat moderate to severe psoriasis. However, remission can be difficult to achieve and maintain in this patient population. Long-term use of a single systemic agent may result in loss of efficacy, adverse effects, and cumulative toxicities. Combination therapy with two systemic agents with alternate mechanisms of action may provide a synergistic therapeutic enhancement without a significant increase in adverse effects. Objective: To assess the therapeutic efficacy and adverse effect profile of the combination regimen acitretin and adalimumab for the treatment of moderate to severe psoriasis. Method: Retrospective analysis of 21 patients with moderate to severe psoriasis treated with a combination regimen of acitretin and adalimumab between January 2004 and June 2009. Of these 21 patients, 18 had plaque psoriasis, and three had palmoplantar psoriasis. All patients demonstrated an inadequate response to systemic monotherapies including acitretin (29%) and biological agents (71%) before this study. Patients were then started on a combination therapy of adalimumab 40mg every other week and acitretin 10 or 25 mg daily. Severity of the psoriasis was assessed by the percent of body surface affected (BSA). A change in BSA from baseline was used to assess the efficacy of this treatment. Moderate improvement was defined as [50% decrease in BSA and marked improvement was defined as [75% decrease. Presence of psoriatic arthritis was noted. All adverse events were reported in this study. Results: Of the 21 patients with moderate to severe psoriasis, the mean (6 SE) BSA before treatment initiation was 30% 6 5.8. Compared to this baseline, follow-up at 8 weeks, 14 weeks, and 20 weeks demonstrated a mean (6 SE) BSA of 24% 6 6.1 (P ¼ .003), 15% 6 5.2 (P ¼ .012), and 13% 6 6.0 (P ¼ .017), respectively. Percentage of patients with moderate improvement was 33% at 8 weeks, 65% at 14 weeks, and 64% at 20 weeks. Percentage of patients with marked improvement was 5% at 8 weeks, 18% at 14 weeks, and 21% at 20 weeks. Patients with palmoplantar psoriasis exhibited functional improvement in their daily activities at a mean of 4 weeks. Psoriatic arthritis was present in 19 patients; of these, 79% reported clinical resolution of joint symptoms during treatment. The combination regimen was well tolerated. Adverse effects include generalized pruritis (1/21), dry skin (1/21), sticky skin (1/21), upper respiratory tract infection (2/21), and cellulitis (2/21). All laboratory abnormalities were mild and did not warrant discontinuation of treatment.
Objective: To assess the long-term safety data for all patients treated with adalimumab in all phase II, II/III, III and IIIb clinical trials of moderate to severe psoriasis. Methods: Safety data from all patients receiving $ 1 dose of adalimumab in 11 clinical trials (7 RCTs and 4 extension trials) of adalimumab in moderate to severe psoriasis were included in this analysis. Two overlapping safety datasets were created by pooling all data collected from clinical trials through April 15, 2007 and through November 6, 2008, respectively. Most patients received adalimumab subcutaneously at a dosage of 40 mg every other week, begun either 1 week after an initial dose of 80mg, or after a period of treatment with placebo. Adverse events (AE) were counted if they occurred up to 70 days after discontinuation of adalimumab. The definition of ‘‘allergic reactions’’ was expanded for the November 6, 2008 dataset to include ‘‘urticaria’’ and other terms. Standardized Incidence Ratios (SIRs) were determined using the SEER data base for comparison. Results: The 2007 and 2008 datasets included 1819 and 2197 patients, respectively, with total exposures of 2424.7 and 4351.9 patient-years (PYs). Overall AE rates (as events per PY) for the 2007 and 2008 data sets were 2.975 and 2.757, and serious AE rates were 0.065 and 0.072, respectively. Rates of other types of AEs for the 2007 and 2008 data sets, respectively, were: infections, 0.839 and 0.802; serious infections, 0.013 and 0.014; opportunistic infections, 0.002 and 0.003; nonmelanoma skin cancer (NMSC), 0.008 and 0.007; demyelinating disorders, 0.000 and \0.001; congestive heart failure, \0.001 and 0.002; tuberculosis, 0.002 and \0.001; allergic reactions, 0.002 and 0.009; and malignancies (excluding NMSC), 0.005 and 0.006. SIR (95% CI) for malignancies (excluding NMSC) were 0.80 (0.41-1.39) and 0.89 (0.57-1.32), respectively, for 2007 and 2008. Rates were \0.001 for lupus-like syndrome in both data sets. No lymphomas were observed. Conclusions: AE rates from pooled results for all clinical trials of adalimumab in psoriasis were low and generally stable over time. Commercial support: Abbott sponsored the study and the poster.
Conclusions: In this series of patients, acitretin and adalimumab combination regimen shows efficacy without significant increase in adverse events in the treatment of moderate to severe psoriasis refractory to systemic monotherapy. Further clinical studies need to be conducted to address the efficacy and safety of this combination regimen. Commercial support: None identified.
P3336 The ustekinumab safety experience in patients with moderate to severe psoriasis: Results from pooled analyses of phase II and phase III clinical trial data Kenneth Gordon, MD, NorthShore University Health Systems, Skokie, IL, United States; Craig Leonardi, MD, Central Dermatology, Saint Louis, MO, United States; Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; Newman Yeilding, MD, Centocor Research and Development, Inc, Malvern, PA, United States Aim: To analyze the cumulative safety experience of ustekinumab, a novel human monoclonal antibody against interleukin 12/23p40, across phase II and III psoriasis clinical trials through 18 months of treatment. Methods: Safety data were pooled from all phase II and III double-blind, placebocontrolled studies, including one phase II study (n ¼ 320 patients with up to 36 weeks safety experience), and two phase III studies: PHOENIX 1 (n ¼ 766 patients with up to 76 weeks safety experience) and PHOENIX 2 (n ¼ 1230 patients with up to 52 weeks safety experience). Ustekinumab 45mg and 90mg dosing were studied in each trial (phase II: 1 injection or 4 weekly injections; phase III: injections at week 0, 4, and every 12 weeks thereafter). Placebo-treated patients crossed over to ustekinumab at week 20 (phase II) or week 12 (phase III). Results: Across the phase II and III trials, a total of 2266 patients were exposed to ustekinumab, of whom 1970 patients were exposed for $ 6 months, 1285 exposed for $ 12 months, and 373 for $ 18 months. During the common 12-week controlled period of the trials, 50.4%,57.6%,and 51.6% of patients treated with placebo, 45-mg dosing, and 90-mg dosing, respectively, experienced $ 1 adverse event (AE). In these respective groups, 1.4%, 1.6%, and 1.4% experienced $ 1 serious AE (SAE); 23.2%, 27.0%, and 24.1% experienced $ 1 infection; and 1.9%, 1.1%, and 1.4% experienced an AE leading to treatment discontinuation Cumulative rates of AEs, SAEs, infections, and AEs leading to study agent discontinuation during the controlled and uncontrolled periods did not increase over time with increased duration of exposure or with increased cumulative exposure. Noncutaneous malignancies in the controlled period occurred at 0.25 per 100 PY for ustekinumab-treated patients compared to 0.57 per 100 PY for placebo-treated patients. The incidence of noncutaneous malignancies during the controlled and uncontrolled periods was 0.36 per 100 PY for ustekinumab-treated patients. Conclusion: Ustekinumab was well tolerated with a favorable safety profile which remained consistent over time with up to approximately 18 months of treatment. Commercial support: Centocor Research and Development.
AB132
J AM ACAD DERMATOL
P3338 Twice-weekly use of clobetasol propionate 0.05% shampoo is effective and safe for the long-term control of scalp psoriasis Yves Poulin, MD, Centre de Recherche Dermatologique du Quebec Me´tropolitain, Quebec City, Quebec, Canada; Kim Papp, K. Papp Clinical Research, Waterloo, Canada; Lyn Guenther, MD, MHS, The Guenther Dermatolgy Research Centre, London, Ontario, Canada; Robert Bissonnette, MD, Innovaderm Research Laval, Laval, Quebec, Canada An unmet need of scalp psoriasis treatment is the long-term maintenance of remission. A short-contact shampoo formulation of 0.05% clobetasol propionate, a super-potent corticosteroid was developed to optimize efficacy and reduce potential adverse effects. A study was conducted to assess the efficacy and safety profile of twice weekly use of this 0.05% clobetasol propionate (CP) shampoo formulation as maintenance treatment for scalp psoriasis. Patients aged 18 years or older, with moderate to severe scalp psoriasis, defined by a Global Severity Score (GSS) of 3 or 4 (on a 0 to 5 scale), first entered an initial phase where they applied CP shampoo once daily for up to 4 weeks. Patients showing a GSS # 2 then entered a doubleblind maintenance phase in which they were randomized to either CP shampoo or its vehicle, to be used twice weekly for up to 6 months. If relapse occurred (GSS[2), patients of both groups went back to a 4-week daily treatment with CP shampoo after which they re-entered in double-blind to the twice weekly maintenance regimen if the GSS was # 2. Patients with a GSS [ 2 at two consecutive visits were withdrawn from the study. The primary efficacy measure was the time to first relapse. Safety was evaluated throughout the trial by assessment of burning, skin atrophy and telangiectasia, and retrieval of adverse events. A morning serum cortisol dosage was done at the last visit. Out of the 288 enrolled in the initial phase, 217 patients (75%) entered the maintenance phase. Mean age was 50.4 years (range, 1882). Mean GSS at maintenance baseline was 1.5 in both groups. The median time to first relapse was 58 days with CP shampoo versus 29 days with the vehicle (P \ .0001), and mean time to first relapse was 93.7 days (6 6.6) with CP shampoo versus 55 days (64.8) with the vehicle (P \.0001). During the twice weekly maintenance regimen, 44.3% patients had no relapse with CP shampoo versus 15.5% with the vehicle after 3 months, and 31.1% and 8.1% patients, respectively (P \.001), after 6 months. During the entire study (initial phase and maintenance phase), the mean number of days of applications of CP shampoo was 80.5 in the CP shampoo arm and 60.3 in the vehicle arm. CP shampoo appeared to be safe. The vast majority of patients had no burning sensation. No skin atrophy, telangiectasia, or significant decrease of serum cortisol levels was observed. Adverse event rate was comparable in both treatment groups. Twice-weekly use of clobetasol propionate 0.05% shampoo is effective and safe for long-term maintenance treatment of scalp psoriasis. Commercial support: Study and poster support provided by Galderma Laboratories, L.P.
MARCH 2010