Risankizumab outpaced ustekinumab for complete clearance of plaque psoriasis

SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.

In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.

Bruce Jancin/Frontline Medical News

“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”

Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.

Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.

The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.

In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.

Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.

At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.

In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).

As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).

Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.

A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.

“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”

The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).

Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.

The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.

"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."

AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.

msullivan@frontlinemedcom.com

SOURCE: Gordon et al. AAD, Abstract 6495

SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.

In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.

Bruce Jancin/Frontline Medical News

“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”

Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.

Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.

The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.

In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.

Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.

At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.

In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).

As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).

Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.

A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.

“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”

The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).

Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.

The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.

"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."

AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.

msullivan@frontlinemedcom.com

SOURCE: Gordon et al. AAD, Abstract 6495

SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.

In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.

Bruce Jancin/Frontline Medical News

“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”

Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.

Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.

The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.

In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.

Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.

At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.

In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).

As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).

Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.

A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.

“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”

The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).

Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.

The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.

"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."

AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.

msullivan@frontlinemedcom.com

SOURCE: Gordon et al. AAD, Abstract 6495