Fixed maintenance secukinumab beats as-needed dosing

ISTANBUL – Psoriasis patients who initially achieve a high-level response to secukinumab are significantly more likely to retain it over the long haul if they follow a fixed maintenance therapy schedule of once-monthly subcutaneous dosing rather than dosing as needed in the event of the start of relapse, according to the phase III SCULPTURE trial.

Secukinumab is an investigational fully human IgG1 monoclonal antibody targeting interleukin-17A, a key player in psoriasis, because it generates downstream proinflammatory cytokines and stimulates keratinocyte growth. Earlier studies indicated the investigational biologic had unprecedented clinical efficacy and rapidity of response. These observations gave rise to the hypothesis in SCULPTURE that maintenance dosing as needed upon relapse would prove noninferior to conventional fixed once-monthly maintenance therapy.

If the study hypothesis proved valid, it would mean less exposure to potential medication side effects, lower drug costs, and greater patient convenience. However, the hypothesis wasn’t borne out in the 966-patient, double-blind, randomized SCULPTURE (Study Comparing Retreatment Upon Start of Relapse), Dr. Ulrich Mrowietz reported at the annual congress of the European Academy of Dermatology and Venereology.

SCULPTURE participants had moderate-to-severe chronic plaque psoriasis despite prior systemic therapies, including biologic agents in many cases. They were randomized double blind to induction therapy involving five once-weekly subcutaneous injections of secukinumab at either 150 or 300 mg. At week 8, 843 participants with a Psoriasis Area and Severity Index (PASI) 75 response were re-randomized to maintenance therapy at the same dose, to be delivered either once monthly or as needed for relapse. The definition of relapse in this study required two elements: loss of PASI 75 response, and at least a 20% fall from the maximum PASI improvement, compared with baseline.

At week 52, 78.2% of patients randomized to 300 mg of secukinumab on a fixed once-monthly schedule still maintained a PASI 75 response. This was a significantly better outcome than the 67.7% PASI 75 rate in patients assigned to secukinumab 300 mg as needed, the 62.1% rate in those on secukinumab 150 mg once monthly, and the 52% PASI 75 rate in patients on secukinumab 150 mg as needed, reported Dr. Mrowietz of the University Medical Center Schleswig-Holstein, Kiel (Germany).

He found a bright spot in the negative results: While patients assigned to as-needed maintenance therapy achieved roughly an absolute 10% lower PASI 75 rate at 1 year, those in the secukinumab 150-mg group did so with only 46% the number of doses received by patients in the fixed monthly therapy group, while those in the retreatment-as-needed with secukinumab 300-mg group got only 39% of the number of doses, compared with patients on fixed monthly therapy.

"Fixed monthly dosing is the best maintenance regimen. But, in selected patients, there may be an opportunity with secukinumab to deviate from the usual fixed dosing regimen in favor of an as-needed approach," he said.

This tradeoff of an absolute 10% reduction in efficacy in return for a dosing regimen that entails less than half as much medication over the course of a year could prove of interest to payers, he noted.

The key, according to Dr. Mrowietz, will be to try to identify criteria helpful in selecting patients with an increased likelihood of a high-level response to the retreat-as-needed management strategy. The phase III trial was completed so recently that those necessary subanalyses have yet to be done.

However, Dr. Kristian Reich, another investigator involved in the secukinumab clinical trials program, drew a different message from SCULPTURE. He observed that these newer biologic agents are so effective that the bar has been raised with regard to patient expectations. Many patients won’t be satisfied with a PASI 75 response once a PASI 90 is achievable. And with fixed monthly maintenance secukinumab, it often is.

Indeed, the week-52 PASI 90 rate in SCULPTURE was a highly robust 59.7% in patients on fixed monthly secukinumab 300 mg and 45.8% for fixed monthly low-dose therapy, compared with the unimpressive 13.8% and 11.2% PASI 90 rates with high- and low-dose as-needed therapy.

"My take from this is that the best way to use this drug for continuous disease control is to give the drug every 4 weeks. What this study tells us is for those patients where you have to stop, where you have to use on-and-off therapy because they go away for 2 months to Africa, or they have a major operation, or for other reasons, these data are reassuring that we can use the drug safely on an intermittent basis," said Dr. Reich of Georg-August University in Göttingen, Germany.

Prior to SCULPTURE, he and other investigators were concerned that intermittent secukinumab therapy might promote the development of harmful antidrug antibodies. But antidrug antibodies arose in only three patients on fixed monthly maintenance therapy and two patients on as-needed therapy, and had no impact upon clinical efficacy or safety, he noted.

Another phase III trial presented in Istanbul was ERASURE (Efficacy and Safety of Subcutaneous Secukinumab for Moderate to Severe Chronic Plaque-Type Psoriasis for Up to 1 Year). Dr. Boni E. Elewski reported on 738 patients with moderate-to-severe chronic plaque psoriasis who were randomized double blind to secukinumab at 150 mg or 300 mg, or to placebo. Participants averaged a PASI score of 22 at baseline, along with 33% body surface area involvement. Psoriatic arthritis was present in 23% of subjects.

The co-primary endpoints in ERASURE were the week 12 PASI 75 response rates and Investigator’s Global Assessment scores of 0/1, indicative of clear or almost clear on a modified 5-point scale. The week-12 PASI 75 rates were 81.6% in the secukinumab 300 mg group, 71.6% with secukinumab 150 mg, and 4.5% with placebo. The week-12 IGA 0/1 rates were 65.3%, 51.2%, and 2.4%, said Dr. Elewski of the University of Alabama, Birmingham.

Among the other notable findings in ERASURE were the 69.8% PASI 90 and 41.6% PASI 100 responses at week 16 in the group assigned to secukinumab 300 mg, the fact that only one patient, on secukinumab 150 mg, developed transient antidrug antibodies, and the complete absence of cardiovascular events during 52 weeks on secukinumab, observed Dr. Elewski, professor of dermatology at the University of Alabama, Birmingham.

Dr. Mrowietz, Dr. Reich, and Dr. Elewski reported having received research grants from and serving as consultants to Novartis, which sponsored the secukinumab clinical trials program. The dermatologists serve in similar capacities with other pharmaceutical companies developing new medications for psoriasis.

bjancin@frontlinemedcom.com

ISTANBUL – Psoriasis patients who initially achieve a high-level response to secukinumab are significantly more likely to retain it over the long haul if they follow a fixed maintenance therapy schedule of once-monthly subcutaneous dosing rather than dosing as needed in the event of the start of relapse, according to the phase III SCULPTURE trial.

Secukinumab is an investigational fully human IgG1 monoclonal antibody targeting interleukin-17A, a key player in psoriasis, because it generates downstream proinflammatory cytokines and stimulates keratinocyte growth. Earlier studies indicated the investigational biologic had unprecedented clinical efficacy and rapidity of response. These observations gave rise to the hypothesis in SCULPTURE that maintenance dosing as needed upon relapse would prove noninferior to conventional fixed once-monthly maintenance therapy.

If the study hypothesis proved valid, it would mean less exposure to potential medication side effects, lower drug costs, and greater patient convenience. However, the hypothesis wasn’t borne out in the 966-patient, double-blind, randomized SCULPTURE (Study Comparing Retreatment Upon Start of Relapse), Dr. Ulrich Mrowietz reported at the annual congress of the European Academy of Dermatology and Venereology.

SCULPTURE participants had moderate-to-severe chronic plaque psoriasis despite prior systemic therapies, including biologic agents in many cases. They were randomized double blind to induction therapy involving five once-weekly subcutaneous injections of secukinumab at either 150 or 300 mg. At week 8, 843 participants with a Psoriasis Area and Severity Index (PASI) 75 response were re-randomized to maintenance therapy at the same dose, to be delivered either once monthly or as needed for relapse. The definition of relapse in this study required two elements: loss of PASI 75 response, and at least a 20% fall from the maximum PASI improvement, compared with baseline.

At week 52, 78.2% of patients randomized to 300 mg of secukinumab on a fixed once-monthly schedule still maintained a PASI 75 response. This was a significantly better outcome than the 67.7% PASI 75 rate in patients assigned to secukinumab 300 mg as needed, the 62.1% rate in those on secukinumab 150 mg once monthly, and the 52% PASI 75 rate in patients on secukinumab 150 mg as needed, reported Dr. Mrowietz of the University Medical Center Schleswig-Holstein, Kiel (Germany).

He found a bright spot in the negative results: While patients assigned to as-needed maintenance therapy achieved roughly an absolute 10% lower PASI 75 rate at 1 year, those in the secukinumab 150-mg group did so with only 46% the number of doses received by patients in the fixed monthly therapy group, while those in the retreatment-as-needed with secukinumab 300-mg group got only 39% of the number of doses, compared with patients on fixed monthly therapy.

"Fixed monthly dosing is the best maintenance regimen. But, in selected patients, there may be an opportunity with secukinumab to deviate from the usual fixed dosing regimen in favor of an as-needed approach," he said.

This tradeoff of an absolute 10% reduction in efficacy in return for a dosing regimen that entails less than half as much medication over the course of a year could prove of interest to payers, he noted.

The key, according to Dr. Mrowietz, will be to try to identify criteria helpful in selecting patients with an increased likelihood of a high-level response to the retreat-as-needed management strategy. The phase III trial was completed so recently that those necessary subanalyses have yet to be done.

However, Dr. Kristian Reich, another investigator involved in the secukinumab clinical trials program, drew a different message from SCULPTURE. He observed that these newer biologic agents are so effective that the bar has been raised with regard to patient expectations. Many patients won’t be satisfied with a PASI 75 response once a PASI 90 is achievable. And with fixed monthly maintenance secukinumab, it often is.

Indeed, the week-52 PASI 90 rate in SCULPTURE was a highly robust 59.7% in patients on fixed monthly secukinumab 300 mg and 45.8% for fixed monthly low-dose therapy, compared with the unimpressive 13.8% and 11.2% PASI 90 rates with high- and low-dose as-needed therapy.

"My take from this is that the best way to use this drug for continuous disease control is to give the drug every 4 weeks. What this study tells us is for those patients where you have to stop, where you have to use on-and-off therapy because they go away for 2 months to Africa, or they have a major operation, or for other reasons, these data are reassuring that we can use the drug safely on an intermittent basis," said Dr. Reich of Georg-August University in Göttingen, Germany.

Prior to SCULPTURE, he and other investigators were concerned that intermittent secukinumab therapy might promote the development of harmful antidrug antibodies. But antidrug antibodies arose in only three patients on fixed monthly maintenance therapy and two patients on as-needed therapy, and had no impact upon clinical efficacy or safety, he noted.

Another phase III trial presented in Istanbul was ERASURE (Efficacy and Safety of Subcutaneous Secukinumab for Moderate to Severe Chronic Plaque-Type Psoriasis for Up to 1 Year). Dr. Boni E. Elewski reported on 738 patients with moderate-to-severe chronic plaque psoriasis who were randomized double blind to secukinumab at 150 mg or 300 mg, or to placebo. Participants averaged a PASI score of 22 at baseline, along with 33% body surface area involvement. Psoriatic arthritis was present in 23% of subjects.

The co-primary endpoints in ERASURE were the week 12 PASI 75 response rates and Investigator’s Global Assessment scores of 0/1, indicative of clear or almost clear on a modified 5-point scale. The week-12 PASI 75 rates were 81.6% in the secukinumab 300 mg group, 71.6% with secukinumab 150 mg, and 4.5% with placebo. The week-12 IGA 0/1 rates were 65.3%, 51.2%, and 2.4%, said Dr. Elewski of the University of Alabama, Birmingham.

Among the other notable findings in ERASURE were the 69.8% PASI 90 and 41.6% PASI 100 responses at week 16 in the group assigned to secukinumab 300 mg, the fact that only one patient, on secukinumab 150 mg, developed transient antidrug antibodies, and the complete absence of cardiovascular events during 52 weeks on secukinumab, observed Dr. Elewski, professor of dermatology at the University of Alabama, Birmingham.

Dr. Mrowietz, Dr. Reich, and Dr. Elewski reported having received research grants from and serving as consultants to Novartis, which sponsored the secukinumab clinical trials program. The dermatologists serve in similar capacities with other pharmaceutical companies developing new medications for psoriasis.

bjancin@frontlinemedcom.com

ISTANBUL – Psoriasis patients who initially achieve a high-level response to secukinumab are significantly more likely to retain it over the long haul if they follow a fixed maintenance therapy schedule of once-monthly subcutaneous dosing rather than dosing as needed in the event of the start of relapse, according to the phase III SCULPTURE trial.

Secukinumab is an investigational fully human IgG1 monoclonal antibody targeting interleukin-17A, a key player in psoriasis, because it generates downstream proinflammatory cytokines and stimulates keratinocyte growth. Earlier studies indicated the investigational biologic had unprecedented clinical efficacy and rapidity of response. These observations gave rise to the hypothesis in SCULPTURE that maintenance dosing as needed upon relapse would prove noninferior to conventional fixed once-monthly maintenance therapy.

If the study hypothesis proved valid, it would mean less exposure to potential medication side effects, lower drug costs, and greater patient convenience. However, the hypothesis wasn’t borne out in the 966-patient, double-blind, randomized SCULPTURE (Study Comparing Retreatment Upon Start of Relapse), Dr. Ulrich Mrowietz reported at the annual congress of the European Academy of Dermatology and Venereology.

SCULPTURE participants had moderate-to-severe chronic plaque psoriasis despite prior systemic therapies, including biologic agents in many cases. They were randomized double blind to induction therapy involving five once-weekly subcutaneous injections of secukinumab at either 150 or 300 mg. At week 8, 843 participants with a Psoriasis Area and Severity Index (PASI) 75 response were re-randomized to maintenance therapy at the same dose, to be delivered either once monthly or as needed for relapse. The definition of relapse in this study required two elements: loss of PASI 75 response, and at least a 20% fall from the maximum PASI improvement, compared with baseline.

At week 52, 78.2% of patients randomized to 300 mg of secukinumab on a fixed once-monthly schedule still maintained a PASI 75 response. This was a significantly better outcome than the 67.7% PASI 75 rate in patients assigned to secukinumab 300 mg as needed, the 62.1% rate in those on secukinumab 150 mg once monthly, and the 52% PASI 75 rate in patients on secukinumab 150 mg as needed, reported Dr. Mrowietz of the University Medical Center Schleswig-Holstein, Kiel (Germany).

He found a bright spot in the negative results: While patients assigned to as-needed maintenance therapy achieved roughly an absolute 10% lower PASI 75 rate at 1 year, those in the secukinumab 150-mg group did so with only 46% the number of doses received by patients in the fixed monthly therapy group, while those in the retreatment-as-needed with secukinumab 300-mg group got only 39% of the number of doses, compared with patients on fixed monthly therapy.

"Fixed monthly dosing is the best maintenance regimen. But, in selected patients, there may be an opportunity with secukinumab to deviate from the usual fixed dosing regimen in favor of an as-needed approach," he said.

This tradeoff of an absolute 10% reduction in efficacy in return for a dosing regimen that entails less than half as much medication over the course of a year could prove of interest to payers, he noted.

The key, according to Dr. Mrowietz, will be to try to identify criteria helpful in selecting patients with an increased likelihood of a high-level response to the retreat-as-needed management strategy. The phase III trial was completed so recently that those necessary subanalyses have yet to be done.

However, Dr. Kristian Reich, another investigator involved in the secukinumab clinical trials program, drew a different message from SCULPTURE. He observed that these newer biologic agents are so effective that the bar has been raised with regard to patient expectations. Many patients won’t be satisfied with a PASI 75 response once a PASI 90 is achievable. And with fixed monthly maintenance secukinumab, it often is.

Indeed, the week-52 PASI 90 rate in SCULPTURE was a highly robust 59.7% in patients on fixed monthly secukinumab 300 mg and 45.8% for fixed monthly low-dose therapy, compared with the unimpressive 13.8% and 11.2% PASI 90 rates with high- and low-dose as-needed therapy.

"My take from this is that the best way to use this drug for continuous disease control is to give the drug every 4 weeks. What this study tells us is for those patients where you have to stop, where you have to use on-and-off therapy because they go away for 2 months to Africa, or they have a major operation, or for other reasons, these data are reassuring that we can use the drug safely on an intermittent basis," said Dr. Reich of Georg-August University in Göttingen, Germany.

Prior to SCULPTURE, he and other investigators were concerned that intermittent secukinumab therapy might promote the development of harmful antidrug antibodies. But antidrug antibodies arose in only three patients on fixed monthly maintenance therapy and two patients on as-needed therapy, and had no impact upon clinical efficacy or safety, he noted.

Another phase III trial presented in Istanbul was ERASURE (Efficacy and Safety of Subcutaneous Secukinumab for Moderate to Severe Chronic Plaque-Type Psoriasis for Up to 1 Year). Dr. Boni E. Elewski reported on 738 patients with moderate-to-severe chronic plaque psoriasis who were randomized double blind to secukinumab at 150 mg or 300 mg, or to placebo. Participants averaged a PASI score of 22 at baseline, along with 33% body surface area involvement. Psoriatic arthritis was present in 23% of subjects.

The co-primary endpoints in ERASURE were the week 12 PASI 75 response rates and Investigator’s Global Assessment scores of 0/1, indicative of clear or almost clear on a modified 5-point scale. The week-12 PASI 75 rates were 81.6% in the secukinumab 300 mg group, 71.6% with secukinumab 150 mg, and 4.5% with placebo. The week-12 IGA 0/1 rates were 65.3%, 51.2%, and 2.4%, said Dr. Elewski of the University of Alabama, Birmingham.

Among the other notable findings in ERASURE were the 69.8% PASI 90 and 41.6% PASI 100 responses at week 16 in the group assigned to secukinumab 300 mg, the fact that only one patient, on secukinumab 150 mg, developed transient antidrug antibodies, and the complete absence of cardiovascular events during 52 weeks on secukinumab, observed Dr. Elewski, professor of dermatology at the University of Alabama, Birmingham.

Dr. Mrowietz, Dr. Reich, and Dr. Elewski reported having received research grants from and serving as consultants to Novartis, which sponsored the secukinumab clinical trials program. The dermatologists serve in similar capacities with other pharmaceutical companies developing new medications for psoriasis.

bjancin@frontlinemedcom.com