EADV: Long-term apremilast results show what to expect for psoriasis

COPENHAGEN – What can physicians and their psoriasis patients realistically expect from long-term apremilast therapy?

“I think the take-home number is a 50%-plus PASI-75 response after 1 year among patients with moderate to severe plaque psoriasis,” Dr. Kristian Reich said at the annual congress of the European Academy of Dermatology and Venereology.

He presented what he considers to be the first solid data addressing this key question. The data come from a new analysis of the 52-week results of the LIBERATE trial.

“Due to the randomized withdrawal design and long-term treatment only of responders in the original pivotal phase III ESTEEM program, I think we’ve had no real understanding from clinical trials of what the long-term efficacy of apremilast [Otezla] is. Of course, with psoriasis being a chronic disease, this is really what we want to know. And we can get this data very nicely from the LIBERATE study. I should point out that although LIBERATE is a relatively small study, every single patient is included here. So I think this is a very robust analysis of 1-year efficacy data,” said Dr. Reich, managing partner of Dermatologikum Hamburg (Germany).

In contrast to the inclusive analysis performed in LIBERATE, in the pivotal ESTEEM I trial a mere 77 of 562 psoriasis patients randomized to apremilast were on the oral phosphodiesterase type 4 inhibitor for the full 52-week study period, with 61% of that superselect subgroup showing a PASI-75 response (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

LIBERATE included 250 psoriasis patients. Their baseline Psoriasis Area and Severity Index (PASI) score was about 20, with 27% body surface area involved, a body mass index of 29 kg/m², 89 kg of body weight, and a mean Dermatology Life Quality Index (DLQI) score of 13. Seventy percent to 80% of subjects had previously used conventional systemic therapies, but no one was allowed to have prior use of biologic therapies.

Patients were randomized to one of three study arms: 16 weeks of oral apremilast at the approved dose of 30 mg twice daily plus a weekly placebo injection, subcutaneous etanercept (Enbrel) at 50 mg once weekly plus a placebo tablet, or dual placebos. At 16 weeks, all patients were switched to apremilast at 30 mg twice daily with no placebos through week 52.

The PASI-75 response rate at week 16 was 11.9% in the placebo group, 39.8% with apremilast, and 48.2% with etanercept.

“I am surprised to see in the more recent studies the high response to etanercept. This is fantastic data. Etanercept seems to ripen like old wine. It’s getting better the longer we have it,” the dermatologist commented.

The PASI-75 rates at 1 year were 46.4% with placebo/apremilast, 50.6% with apremilast throughout, and 55.4% with etanercept/apremilast.

The mean improvement in DLQI from baseline to 52 weeks – a secondary endpoint – was 6.6 points with placebo/apremilast, 8.0 with apremilast/apremilast, and 8.9 points with etanercept/apremilast. A noteworthy finding was that during the first 16 weeks apremilast brought a clinically meaningful improvement in quality of life significantly faster than etanercept did, with a significant difference seen between the two study arms even in the first 1-2 weeks.

The likely explanation for this benefit is that the mean reduction in pruritus visual analog scale scores was significantly greater with apremilast than etanercept through the first 8 weeks. Although pruritus is traditionally thought of more in the context of atopic dermatitis, it’s actually also the No. 1 complaint among psoriasis patients, according to Dr. Reich.

“This is a special thing with apremilast, that the pruritus really goes down very significantly early on. It raises an interesting question about what the role of phosphodiesterase-4 inhibition might be in pruritus. I couldn’t give you a molecular explanation, but I think because pruritus is so annoying and it definitely affects quality of life, this could be a possible explanation for why there is more rapid improvement in quality of life independent of the PASI improvement,” he said.

Switching from etanercept to apremilast didn’t result in any clinically significant safety findings through week 52. No meaningful laboratory changes occurred during 52 weeks of monitoring. There were no cases of suicidal ideation, no increase in serious infections, and only a single cardiac event. The most common apremilast-associated side effects seen in LIBERATE were loose stools in 8%-15% of patients, nausea in 10%, and headache in 13%. These adverse events were mild to moderate in nature and decreased in prevalence over time. The maximum weight loss noted over the course of 52 weeks occurred in the placebo-to-apremilast group, with a mean 1.3-kg reduction.

“I would call the LIBERATE results a validation of the earlier data showing a very clean safety profile with this drug,” Dr. Reich said.

This is reflected in the product labeling, which unlike other systemic therapies for psoriasis includes no requirements for laboratory monitoring or tuberculosis testing.

Both the LIBERATE and the ESTEEM trials were sponsored by Celgene. Dr. Reich received research grants as an investigator in both programs.

[email protected]

COPENHAGEN – What can physicians and their psoriasis patients realistically expect from long-term apremilast therapy?

“I think the take-home number is a 50%-plus PASI-75 response after 1 year among patients with moderate to severe plaque psoriasis,” Dr. Kristian Reich said at the annual congress of the European Academy of Dermatology and Venereology.

He presented what he considers to be the first solid data addressing this key question. The data come from a new analysis of the 52-week results of the LIBERATE trial.

“Due to the randomized withdrawal design and long-term treatment only of responders in the original pivotal phase III ESTEEM program, I think we’ve had no real understanding from clinical trials of what the long-term efficacy of apremilast [Otezla] is. Of course, with psoriasis being a chronic disease, this is really what we want to know. And we can get this data very nicely from the LIBERATE study. I should point out that although LIBERATE is a relatively small study, every single patient is included here. So I think this is a very robust analysis of 1-year efficacy data,” said Dr. Reich, managing partner of Dermatologikum Hamburg (Germany).

In contrast to the inclusive analysis performed in LIBERATE, in the pivotal ESTEEM I trial a mere 77 of 562 psoriasis patients randomized to apremilast were on the oral phosphodiesterase type 4 inhibitor for the full 52-week study period, with 61% of that superselect subgroup showing a PASI-75 response (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

LIBERATE included 250 psoriasis patients. Their baseline Psoriasis Area and Severity Index (PASI) score was about 20, with 27% body surface area involved, a body mass index of 29 kg/m², 89 kg of body weight, and a mean Dermatology Life Quality Index (DLQI) score of 13. Seventy percent to 80% of subjects had previously used conventional systemic therapies, but no one was allowed to have prior use of biologic therapies.

Patients were randomized to one of three study arms: 16 weeks of oral apremilast at the approved dose of 30 mg twice daily plus a weekly placebo injection, subcutaneous etanercept (Enbrel) at 50 mg once weekly plus a placebo tablet, or dual placebos. At 16 weeks, all patients were switched to apremilast at 30 mg twice daily with no placebos through week 52.

The PASI-75 response rate at week 16 was 11.9% in the placebo group, 39.8% with apremilast, and 48.2% with etanercept.

“I am surprised to see in the more recent studies the high response to etanercept. This is fantastic data. Etanercept seems to ripen like old wine. It’s getting better the longer we have it,” the dermatologist commented.

The PASI-75 rates at 1 year were 46.4% with placebo/apremilast, 50.6% with apremilast throughout, and 55.4% with etanercept/apremilast.

The mean improvement in DLQI from baseline to 52 weeks – a secondary endpoint – was 6.6 points with placebo/apremilast, 8.0 with apremilast/apremilast, and 8.9 points with etanercept/apremilast. A noteworthy finding was that during the first 16 weeks apremilast brought a clinically meaningful improvement in quality of life significantly faster than etanercept did, with a significant difference seen between the two study arms even in the first 1-2 weeks.

The likely explanation for this benefit is that the mean reduction in pruritus visual analog scale scores was significantly greater with apremilast than etanercept through the first 8 weeks. Although pruritus is traditionally thought of more in the context of atopic dermatitis, it’s actually also the No. 1 complaint among psoriasis patients, according to Dr. Reich.

“This is a special thing with apremilast, that the pruritus really goes down very significantly early on. It raises an interesting question about what the role of phosphodiesterase-4 inhibition might be in pruritus. I couldn’t give you a molecular explanation, but I think because pruritus is so annoying and it definitely affects quality of life, this could be a possible explanation for why there is more rapid improvement in quality of life independent of the PASI improvement,” he said.

Switching from etanercept to apremilast didn’t result in any clinically significant safety findings through week 52. No meaningful laboratory changes occurred during 52 weeks of monitoring. There were no cases of suicidal ideation, no increase in serious infections, and only a single cardiac event. The most common apremilast-associated side effects seen in LIBERATE were loose stools in 8%-15% of patients, nausea in 10%, and headache in 13%. These adverse events were mild to moderate in nature and decreased in prevalence over time. The maximum weight loss noted over the course of 52 weeks occurred in the placebo-to-apremilast group, with a mean 1.3-kg reduction.

“I would call the LIBERATE results a validation of the earlier data showing a very clean safety profile with this drug,” Dr. Reich said.

This is reflected in the product labeling, which unlike other systemic therapies for psoriasis includes no requirements for laboratory monitoring or tuberculosis testing.

Both the LIBERATE and the ESTEEM trials were sponsored by Celgene. Dr. Reich received research grants as an investigator in both programs.

[email protected]

COPENHAGEN – What can physicians and their psoriasis patients realistically expect from long-term apremilast therapy?

“I think the take-home number is a 50%-plus PASI-75 response after 1 year among patients with moderate to severe plaque psoriasis,” Dr. Kristian Reich said at the annual congress of the European Academy of Dermatology and Venereology.

He presented what he considers to be the first solid data addressing this key question. The data come from a new analysis of the 52-week results of the LIBERATE trial.

“Due to the randomized withdrawal design and long-term treatment only of responders in the original pivotal phase III ESTEEM program, I think we’ve had no real understanding from clinical trials of what the long-term efficacy of apremilast [Otezla] is. Of course, with psoriasis being a chronic disease, this is really what we want to know. And we can get this data very nicely from the LIBERATE study. I should point out that although LIBERATE is a relatively small study, every single patient is included here. So I think this is a very robust analysis of 1-year efficacy data,” said Dr. Reich, managing partner of Dermatologikum Hamburg (Germany).

In contrast to the inclusive analysis performed in LIBERATE, in the pivotal ESTEEM I trial a mere 77 of 562 psoriasis patients randomized to apremilast were on the oral phosphodiesterase type 4 inhibitor for the full 52-week study period, with 61% of that superselect subgroup showing a PASI-75 response (J Am Acad Dermatol. 2015 Jul;73[1]:37-49).

LIBERATE included 250 psoriasis patients. Their baseline Psoriasis Area and Severity Index (PASI) score was about 20, with 27% body surface area involved, a body mass index of 29 kg/m², 89 kg of body weight, and a mean Dermatology Life Quality Index (DLQI) score of 13. Seventy percent to 80% of subjects had previously used conventional systemic therapies, but no one was allowed to have prior use of biologic therapies.

Patients were randomized to one of three study arms: 16 weeks of oral apremilast at the approved dose of 30 mg twice daily plus a weekly placebo injection, subcutaneous etanercept (Enbrel) at 50 mg once weekly plus a placebo tablet, or dual placebos. At 16 weeks, all patients were switched to apremilast at 30 mg twice daily with no placebos through week 52.

The PASI-75 response rate at week 16 was 11.9% in the placebo group, 39.8% with apremilast, and 48.2% with etanercept.

“I am surprised to see in the more recent studies the high response to etanercept. This is fantastic data. Etanercept seems to ripen like old wine. It’s getting better the longer we have it,” the dermatologist commented.

The PASI-75 rates at 1 year were 46.4% with placebo/apremilast, 50.6% with apremilast throughout, and 55.4% with etanercept/apremilast.

The mean improvement in DLQI from baseline to 52 weeks – a secondary endpoint – was 6.6 points with placebo/apremilast, 8.0 with apremilast/apremilast, and 8.9 points with etanercept/apremilast. A noteworthy finding was that during the first 16 weeks apremilast brought a clinically meaningful improvement in quality of life significantly faster than etanercept did, with a significant difference seen between the two study arms even in the first 1-2 weeks.

The likely explanation for this benefit is that the mean reduction in pruritus visual analog scale scores was significantly greater with apremilast than etanercept through the first 8 weeks. Although pruritus is traditionally thought of more in the context of atopic dermatitis, it’s actually also the No. 1 complaint among psoriasis patients, according to Dr. Reich.

“This is a special thing with apremilast, that the pruritus really goes down very significantly early on. It raises an interesting question about what the role of phosphodiesterase-4 inhibition might be in pruritus. I couldn’t give you a molecular explanation, but I think because pruritus is so annoying and it definitely affects quality of life, this could be a possible explanation for why there is more rapid improvement in quality of life independent of the PASI improvement,” he said.

Switching from etanercept to apremilast didn’t result in any clinically significant safety findings through week 52. No meaningful laboratory changes occurred during 52 weeks of monitoring. There were no cases of suicidal ideation, no increase in serious infections, and only a single cardiac event. The most common apremilast-associated side effects seen in LIBERATE were loose stools in 8%-15% of patients, nausea in 10%, and headache in 13%. These adverse events were mild to moderate in nature and decreased in prevalence over time. The maximum weight loss noted over the course of 52 weeks occurred in the placebo-to-apremilast group, with a mean 1.3-kg reduction.

“I would call the LIBERATE results a validation of the earlier data showing a very clean safety profile with this drug,” Dr. Reich said.

This is reflected in the product labeling, which unlike other systemic therapies for psoriasis includes no requirements for laboratory monitoring or tuberculosis testing.

Both the LIBERATE and the ESTEEM trials were sponsored by Celgene. Dr. Reich received research grants as an investigator in both programs.

[email protected]