EADV: Secukinumab shows sustained high efficacy in SCULPTURE through 3 years

COPENHAGEN – Secukinumab maintained consistently high and previously unheard of long-term Psoriasis Area and Severity Index 90 and PASI 100 response rates in psoriasis patients through 3 years of prospective follow-up in an extension of the phase III SCULPTURE trial.

The key to maintaining these high response rates was to give secukinumab (Cosentyx) on a fixed schedule every 4 weeks. SCULPTURE tested the hypothesis that retreatment of initial responders only as needed based upon early evidence of relapse off treatment might be a reasonable alternative strategy. The answer turns out to be emphatically no.

“We can see from the 3-year data that retreatment as needed is probably not a good strategy over the long term. We see four times fewer patients with PASI 90s and 10 times fewer patients with PASI 100s if they are treated as needed. From the patient point of view, quality of life and satisfaction are not optimal with retreatment as needed,” Dr. Diamant Thaci said at the annual congress of the European Academy of Dermatology and Venereology.

The 3-year extension of SCULPTURE also provided reassuring safety data, he noted.

“It’s interesting that with long-term treatment out to 3 years, we don’t see any new safety signals. In fact, the signals we saw in the preapproval studies are slightly diluted here, and now that secukinumab is approved, we’re not seeing them as problems in real life clinical practice,” said Dr. Thaci of University Hospital in Lübeck, Germany.

The 52-week SCULPTURE results were published earlier this year (J Am Acad Dermatol. 2015 Jul;73[1]:27-36). Dr. Thaci’s update extended the findings from 52 weeks through 3 years.

The double-blind phase of the core SCULPTURE study began with 966 patients with moderate to severe plaque psoriasis and a baseline PASI score of about 23. After 12 weeks on subcutaneous secukinumab, the 842 subjects who had achieved 75% or more improvement from their baseline PASI score were randomized to one of four study arms: secukinumab at either 300 mg or 150 mg, administered either every 4 weeks or by retreatment as needed when an individual’s response dropped below PASI 75.

Picking up where the published 52-week results left off, Dr. Thaci focused special attention on the PASI 90 outcomes out to 3 years because he said he believes PASI 90 will become generally accepted as the new treatment target, now that secukinumab is on the market and other supereffective biologic agents are advancing through the developmental pipeline.

At 52 weeks, 68.5% of patients on fixed-dose secukinumab at 300 mg every 4 weeks had a PASI 90 response. At 3 years, after an additional 2 years on this schedule, the PASI 90 rate was still hovering around the two-thirds mark at 63.8%. In contrast, patients on retreatment with 300 mg as needed had a PASI 90 rate of 14.8% at 52 weeks and 13% at 3 years.

Although the Food and Drug Administration recommended the 300-mg dose when it approved secukinumab as a first-in-class biologic in January, the agency added that 150 mg may be acceptable in some patients. But the 150-mg dose was clearly inferior long term in the SCULPTURE extension. At 52 weeks, 50.3% of patients on secukinumab at 150 mg every 4 weeks had a PASI 90 response; at 3 years the rate was 36.8%. With retreatment as needed using 150 mg, the 52-week and 3-year PASI 90 rates were 12% and 11.8%, Dr. Thaci reported.

The PASI 100 (clear skin) response rate at 52 weeks with fixed-dose secukinumab at 300 mg was 43.8%. At 3 years it was 42.6%.

“These excellent responders kept their excellent response by continuing treatment for 3 years,” the dermatologist noted.

The PASI 100 rates with retreatment as needed were 5.3% and 3.8%.

In terms of safety through 3 years of treatment, rates of the adverse events of greatest interest with the use of immunomodulatory therapies – Candida infections, malignancies, serious infections, and major adverse cardiovascular events – were similarly low across all four treatment arms, ranging from 0 to 1.6 events per 100 subject-years. Thus, there was no safety advantage in using the retreatment as needed strategy.

“In the past we were all talking about the risk of Candida infection caused by inhibiting [interleukin]-17. But if you treat patients in real life clinical practice, you may see a signal of Candida infection in the beginning, yet in the long term you don’t see Candida as a significant side effect in our daily practice – and in this trial the incidence decreases,” Dr. Thaci said.

One audience member rose to criticize the way the analysis of the long-term extension of SCULPTURE was structured – namely, that only patients still on secukinumab at the 3-year mark were included in the results. This “as-observed” method inflates the efficacy results, he said. How many patients dropped out over time and weren’t counted? he asked.

Dr. Thaci replied that roughly 90% of patients in the trial at 52 weeks continued on secukinumab out to 3 years.

“It’s not a massive dropout. I wish it were a nonresponder imputation analysis, but in long-term studies, it’s very difficult to show that analysis because the vast majority of the trials that have been presented in the past have been ‘as observed.’ But I don’t think you’ll see a big difference between this as-observed analysis and a nonresponder imputation analysis. This is a very fair and convincing analysis,” he said.

Secukinumab is marketed by Novartis, which sponsored the study. Dr. Thaci serves as an investigator and consultant to Novartis and other pharmaceutical companies.

bjancin@frontlinemedcom.com

COPENHAGEN – Secukinumab maintained consistently high and previously unheard of long-term Psoriasis Area and Severity Index 90 and PASI 100 response rates in psoriasis patients through 3 years of prospective follow-up in an extension of the phase III SCULPTURE trial.

The key to maintaining these high response rates was to give secukinumab (Cosentyx) on a fixed schedule every 4 weeks. SCULPTURE tested the hypothesis that retreatment of initial responders only as needed based upon early evidence of relapse off treatment might be a reasonable alternative strategy. The answer turns out to be emphatically no.

“We can see from the 3-year data that retreatment as needed is probably not a good strategy over the long term. We see four times fewer patients with PASI 90s and 10 times fewer patients with PASI 100s if they are treated as needed. From the patient point of view, quality of life and satisfaction are not optimal with retreatment as needed,” Dr. Diamant Thaci said at the annual congress of the European Academy of Dermatology and Venereology.

The 3-year extension of SCULPTURE also provided reassuring safety data, he noted.

“It’s interesting that with long-term treatment out to 3 years, we don’t see any new safety signals. In fact, the signals we saw in the preapproval studies are slightly diluted here, and now that secukinumab is approved, we’re not seeing them as problems in real life clinical practice,” said Dr. Thaci of University Hospital in Lübeck, Germany.

The 52-week SCULPTURE results were published earlier this year (J Am Acad Dermatol. 2015 Jul;73[1]:27-36). Dr. Thaci’s update extended the findings from 52 weeks through 3 years.

The double-blind phase of the core SCULPTURE study began with 966 patients with moderate to severe plaque psoriasis and a baseline PASI score of about 23. After 12 weeks on subcutaneous secukinumab, the 842 subjects who had achieved 75% or more improvement from their baseline PASI score were randomized to one of four study arms: secukinumab at either 300 mg or 150 mg, administered either every 4 weeks or by retreatment as needed when an individual’s response dropped below PASI 75.

Picking up where the published 52-week results left off, Dr. Thaci focused special attention on the PASI 90 outcomes out to 3 years because he said he believes PASI 90 will become generally accepted as the new treatment target, now that secukinumab is on the market and other supereffective biologic agents are advancing through the developmental pipeline.

At 52 weeks, 68.5% of patients on fixed-dose secukinumab at 300 mg every 4 weeks had a PASI 90 response. At 3 years, after an additional 2 years on this schedule, the PASI 90 rate was still hovering around the two-thirds mark at 63.8%. In contrast, patients on retreatment with 300 mg as needed had a PASI 90 rate of 14.8% at 52 weeks and 13% at 3 years.

Although the Food and Drug Administration recommended the 300-mg dose when it approved secukinumab as a first-in-class biologic in January, the agency added that 150 mg may be acceptable in some patients. But the 150-mg dose was clearly inferior long term in the SCULPTURE extension. At 52 weeks, 50.3% of patients on secukinumab at 150 mg every 4 weeks had a PASI 90 response; at 3 years the rate was 36.8%. With retreatment as needed using 150 mg, the 52-week and 3-year PASI 90 rates were 12% and 11.8%, Dr. Thaci reported.

The PASI 100 (clear skin) response rate at 52 weeks with fixed-dose secukinumab at 300 mg was 43.8%. At 3 years it was 42.6%.

“These excellent responders kept their excellent response by continuing treatment for 3 years,” the dermatologist noted.

The PASI 100 rates with retreatment as needed were 5.3% and 3.8%.

In terms of safety through 3 years of treatment, rates of the adverse events of greatest interest with the use of immunomodulatory therapies – Candida infections, malignancies, serious infections, and major adverse cardiovascular events – were similarly low across all four treatment arms, ranging from 0 to 1.6 events per 100 subject-years. Thus, there was no safety advantage in using the retreatment as needed strategy.

“In the past we were all talking about the risk of Candida infection caused by inhibiting [interleukin]-17. But if you treat patients in real life clinical practice, you may see a signal of Candida infection in the beginning, yet in the long term you don’t see Candida as a significant side effect in our daily practice – and in this trial the incidence decreases,” Dr. Thaci said.

One audience member rose to criticize the way the analysis of the long-term extension of SCULPTURE was structured – namely, that only patients still on secukinumab at the 3-year mark were included in the results. This “as-observed” method inflates the efficacy results, he said. How many patients dropped out over time and weren’t counted? he asked.

Dr. Thaci replied that roughly 90% of patients in the trial at 52 weeks continued on secukinumab out to 3 years.

“It’s not a massive dropout. I wish it were a nonresponder imputation analysis, but in long-term studies, it’s very difficult to show that analysis because the vast majority of the trials that have been presented in the past have been ‘as observed.’ But I don’t think you’ll see a big difference between this as-observed analysis and a nonresponder imputation analysis. This is a very fair and convincing analysis,” he said.

Secukinumab is marketed by Novartis, which sponsored the study. Dr. Thaci serves as an investigator and consultant to Novartis and other pharmaceutical companies.

bjancin@frontlinemedcom.com

COPENHAGEN – Secukinumab maintained consistently high and previously unheard of long-term Psoriasis Area and Severity Index 90 and PASI 100 response rates in psoriasis patients through 3 years of prospective follow-up in an extension of the phase III SCULPTURE trial.

The key to maintaining these high response rates was to give secukinumab (Cosentyx) on a fixed schedule every 4 weeks. SCULPTURE tested the hypothesis that retreatment of initial responders only as needed based upon early evidence of relapse off treatment might be a reasonable alternative strategy. The answer turns out to be emphatically no.

“We can see from the 3-year data that retreatment as needed is probably not a good strategy over the long term. We see four times fewer patients with PASI 90s and 10 times fewer patients with PASI 100s if they are treated as needed. From the patient point of view, quality of life and satisfaction are not optimal with retreatment as needed,” Dr. Diamant Thaci said at the annual congress of the European Academy of Dermatology and Venereology.

The 3-year extension of SCULPTURE also provided reassuring safety data, he noted.

“It’s interesting that with long-term treatment out to 3 years, we don’t see any new safety signals. In fact, the signals we saw in the preapproval studies are slightly diluted here, and now that secukinumab is approved, we’re not seeing them as problems in real life clinical practice,” said Dr. Thaci of University Hospital in Lübeck, Germany.

The 52-week SCULPTURE results were published earlier this year (J Am Acad Dermatol. 2015 Jul;73[1]:27-36). Dr. Thaci’s update extended the findings from 52 weeks through 3 years.

The double-blind phase of the core SCULPTURE study began with 966 patients with moderate to severe plaque psoriasis and a baseline PASI score of about 23. After 12 weeks on subcutaneous secukinumab, the 842 subjects who had achieved 75% or more improvement from their baseline PASI score were randomized to one of four study arms: secukinumab at either 300 mg or 150 mg, administered either every 4 weeks or by retreatment as needed when an individual’s response dropped below PASI 75.

Picking up where the published 52-week results left off, Dr. Thaci focused special attention on the PASI 90 outcomes out to 3 years because he said he believes PASI 90 will become generally accepted as the new treatment target, now that secukinumab is on the market and other supereffective biologic agents are advancing through the developmental pipeline.

At 52 weeks, 68.5% of patients on fixed-dose secukinumab at 300 mg every 4 weeks had a PASI 90 response. At 3 years, after an additional 2 years on this schedule, the PASI 90 rate was still hovering around the two-thirds mark at 63.8%. In contrast, patients on retreatment with 300 mg as needed had a PASI 90 rate of 14.8% at 52 weeks and 13% at 3 years.

Although the Food and Drug Administration recommended the 300-mg dose when it approved secukinumab as a first-in-class biologic in January, the agency added that 150 mg may be acceptable in some patients. But the 150-mg dose was clearly inferior long term in the SCULPTURE extension. At 52 weeks, 50.3% of patients on secukinumab at 150 mg every 4 weeks had a PASI 90 response; at 3 years the rate was 36.8%. With retreatment as needed using 150 mg, the 52-week and 3-year PASI 90 rates were 12% and 11.8%, Dr. Thaci reported.

The PASI 100 (clear skin) response rate at 52 weeks with fixed-dose secukinumab at 300 mg was 43.8%. At 3 years it was 42.6%.

“These excellent responders kept their excellent response by continuing treatment for 3 years,” the dermatologist noted.

The PASI 100 rates with retreatment as needed were 5.3% and 3.8%.

In terms of safety through 3 years of treatment, rates of the adverse events of greatest interest with the use of immunomodulatory therapies – Candida infections, malignancies, serious infections, and major adverse cardiovascular events – were similarly low across all four treatment arms, ranging from 0 to 1.6 events per 100 subject-years. Thus, there was no safety advantage in using the retreatment as needed strategy.

“In the past we were all talking about the risk of Candida infection caused by inhibiting [interleukin]-17. But if you treat patients in real life clinical practice, you may see a signal of Candida infection in the beginning, yet in the long term you don’t see Candida as a significant side effect in our daily practice – and in this trial the incidence decreases,” Dr. Thaci said.

One audience member rose to criticize the way the analysis of the long-term extension of SCULPTURE was structured – namely, that only patients still on secukinumab at the 3-year mark were included in the results. This “as-observed” method inflates the efficacy results, he said. How many patients dropped out over time and weren’t counted? he asked.

Dr. Thaci replied that roughly 90% of patients in the trial at 52 weeks continued on secukinumab out to 3 years.

“It’s not a massive dropout. I wish it were a nonresponder imputation analysis, but in long-term studies, it’s very difficult to show that analysis because the vast majority of the trials that have been presented in the past have been ‘as observed.’ But I don’t think you’ll see a big difference between this as-observed analysis and a nonresponder imputation analysis. This is a very fair and convincing analysis,” he said.

Secukinumab is marketed by Novartis, which sponsored the study. Dr. Thaci serves as an investigator and consultant to Novartis and other pharmaceutical companies.

bjancin@frontlinemedcom.com