EADV: Ixekizumab promising for psoriatic arthritis

COPENHAGEN – Ixekizumab not only shows considerable promise for the treatment of moderate to severe psoriasis, it looks like it may be a winner for comorbid psoriatic arthritis, too.

The investigational IgG4 humanized monoclonal antibody directed against interleukin-17A brought marked improvements in joint pain, systemic inflammatory burden, and quality of life as well as skin disease in patients with both psoriasis and self-reported psoriatic arthritis in a combined analysis of three phase III clinical trials, Dr. Alice B. Gottlieb reported at the annual congress of the European Academy of Dermatology and Venereology.

Of the 3,126 patients with moderate to severe psoriasis who participated in the 12-week, phase III UNCOVER-1, -2, and -3 trials, 751 (24%) also had self-reported psoriatic arthritis; her analysis focused on them.

She was quick to note that the UNCOVER trials were primarily psoriasis studies that relied upon patient self-report of psoriatic arthritis. Nevertheless, it seems likely that the great majority of self-reported psoriatic arthritis patients really did have the rheumatologic disease, since the mean baseline C-reactive protein (CRP) level in that group was 8.43 mg/L, a level far higher than expected in patients with psoriasis only.

In any case, more-rigorous phase III studies of ixekizumab conducted specifically in patients with formally rheumatologist-diagnosed psoriatic arthritis and treated in rheumatology practices are due to be presented at the annual meeting of the American College of Rheumatology in November. And while Dr. Gottlieb wasn’t at liberty to discuss those results, she did hint that the data will be strongly positive.

“If you’re happy about these UNCOVER findings, you’ll be ecstatic about those,” predicted Dr. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

Also coming up at the American College of Rheumatology meeting will be the results of the first-ever head-to-head comparison of an IL-17 inhibitor versus a tumor necrosis factor–alpha blocker in psoriatic arthritis patients. While at present most physicians consider a TNF inhibitor to be the treatment of choice in patients with psoriatic arthritis, that view may change as a result of the forthcoming comparative study, according to the dermatologist.

In each of the three phase III UNCOVER studies, patients were randomized to 12 weeks of subcutaneous ixekizumab at 80 mg every 2 or 4 weeks following a 160-mg loading dose, or to placebo. At baseline, the subgroup with self-reported psoriatic arthritis had a mean Psoriasis Area and Severity Index ( PASI) 0f about 21, a self-rated joint pain severity of 50 on a 0-100 scale, a CRP of 8.43 mg/L, and a Dermatology Life Quality Index (DLQI) score of 14.

Joint pain decreased dramatically in the two ixekizumab groups as early at 2 weeks into the trial, at which point, patients on treatment every 2 weeks averaged a 13.1-point reduction from baseline, with a similar 14.1-point drop noted in those on an every 4 weeks schedule. At week 12, the mean reductions from baseline were 25.2 and 26.8 points, compared with a 1.1-point increase in joint pain among placebo-treated controls.

Inflammatory burden plunged quickly, as evidenced by mean reductions in CRP of 4.63 mg/L and 4.33 mg/L at week 1 with biweekly and monthly dosing, respectively. These reductions were then maintained through week 12.

In terms of improvement in skin symptoms, with ixekizumab dosed every 2 weeks, the PASI 75 response was 89.8% at 12 weeks, the PASI 90 response was 69.3%, and the PASI 100 response (clear skin) was 37.1%. In patients treated every 4 weeks, the rates were 81.1%, 60.8%, and 34.7%.

“There’s good news in both groups, but I think the news is even better in the every-2-weeks group,” Dr. Gottlieb commented.

The mean 12-week decrease from baseline in DLQI was 11.8 points with biweekly dosing and 10.5 with 4-week dosing, compared with 0.8 points in controls. That’s impressive given that a 5-point reduction in DLQI is deemed clinically meaningful, the dermatologist observed. At 12 weeks, 56.5% of patients on ixekizumab every 2 weeks had a DLQI of 0 or 1, as did 54% on monthly dosing and 1.5% of controls.

The ixekizumab-treated groups also showed what Dr. Gottlieb described as “dramatic” improvements – in the 4+ to 5+ point range – in both the mental and physical component scores on the SF-36, another widely used quality of life measure.

Improvements in skin and self-reported joint symptoms appeared to correlate. Patients with a PASI 50 to less-than PASI 75 response had a mean 17-point reduction in joint pain scores, while those with a PASI 75 to less-than PASI 90 response averaged a 25.1-point improvement in joint pain, patients with a PASI 90 to less-than PASI 100 skin response averaged a 27.6-point reduction, and PASI 100 responders had a mean 30.3-point reduction in joint pain scores.

“Obviously, one needs to look at this more carefully in a phase III psoriatic arthritis study. That’ll provide a more robust answer. But this gives a hint,” the dermatologist said.

The UNCOVER program was sponsored by Eli Lilly. Dr. Gottlieb serves as an adviser to Lilly and numerous other pharmaceutical companies.

[email protected]

COPENHAGEN – Ixekizumab not only shows considerable promise for the treatment of moderate to severe psoriasis, it looks like it may be a winner for comorbid psoriatic arthritis, too.

The investigational IgG4 humanized monoclonal antibody directed against interleukin-17A brought marked improvements in joint pain, systemic inflammatory burden, and quality of life as well as skin disease in patients with both psoriasis and self-reported psoriatic arthritis in a combined analysis of three phase III clinical trials, Dr. Alice B. Gottlieb reported at the annual congress of the European Academy of Dermatology and Venereology.

Of the 3,126 patients with moderate to severe psoriasis who participated in the 12-week, phase III UNCOVER-1, -2, and -3 trials, 751 (24%) also had self-reported psoriatic arthritis; her analysis focused on them.

She was quick to note that the UNCOVER trials were primarily psoriasis studies that relied upon patient self-report of psoriatic arthritis. Nevertheless, it seems likely that the great majority of self-reported psoriatic arthritis patients really did have the rheumatologic disease, since the mean baseline C-reactive protein (CRP) level in that group was 8.43 mg/L, a level far higher than expected in patients with psoriasis only.

In any case, more-rigorous phase III studies of ixekizumab conducted specifically in patients with formally rheumatologist-diagnosed psoriatic arthritis and treated in rheumatology practices are due to be presented at the annual meeting of the American College of Rheumatology in November. And while Dr. Gottlieb wasn’t at liberty to discuss those results, she did hint that the data will be strongly positive.

“If you’re happy about these UNCOVER findings, you’ll be ecstatic about those,” predicted Dr. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

Also coming up at the American College of Rheumatology meeting will be the results of the first-ever head-to-head comparison of an IL-17 inhibitor versus a tumor necrosis factor–alpha blocker in psoriatic arthritis patients. While at present most physicians consider a TNF inhibitor to be the treatment of choice in patients with psoriatic arthritis, that view may change as a result of the forthcoming comparative study, according to the dermatologist.

In each of the three phase III UNCOVER studies, patients were randomized to 12 weeks of subcutaneous ixekizumab at 80 mg every 2 or 4 weeks following a 160-mg loading dose, or to placebo. At baseline, the subgroup with self-reported psoriatic arthritis had a mean Psoriasis Area and Severity Index ( PASI) 0f about 21, a self-rated joint pain severity of 50 on a 0-100 scale, a CRP of 8.43 mg/L, and a Dermatology Life Quality Index (DLQI) score of 14.

Joint pain decreased dramatically in the two ixekizumab groups as early at 2 weeks into the trial, at which point, patients on treatment every 2 weeks averaged a 13.1-point reduction from baseline, with a similar 14.1-point drop noted in those on an every 4 weeks schedule. At week 12, the mean reductions from baseline were 25.2 and 26.8 points, compared with a 1.1-point increase in joint pain among placebo-treated controls.

Inflammatory burden plunged quickly, as evidenced by mean reductions in CRP of 4.63 mg/L and 4.33 mg/L at week 1 with biweekly and monthly dosing, respectively. These reductions were then maintained through week 12.

In terms of improvement in skin symptoms, with ixekizumab dosed every 2 weeks, the PASI 75 response was 89.8% at 12 weeks, the PASI 90 response was 69.3%, and the PASI 100 response (clear skin) was 37.1%. In patients treated every 4 weeks, the rates were 81.1%, 60.8%, and 34.7%.

“There’s good news in both groups, but I think the news is even better in the every-2-weeks group,” Dr. Gottlieb commented.

The mean 12-week decrease from baseline in DLQI was 11.8 points with biweekly dosing and 10.5 with 4-week dosing, compared with 0.8 points in controls. That’s impressive given that a 5-point reduction in DLQI is deemed clinically meaningful, the dermatologist observed. At 12 weeks, 56.5% of patients on ixekizumab every 2 weeks had a DLQI of 0 or 1, as did 54% on monthly dosing and 1.5% of controls.

The ixekizumab-treated groups also showed what Dr. Gottlieb described as “dramatic” improvements – in the 4+ to 5+ point range – in both the mental and physical component scores on the SF-36, another widely used quality of life measure.

Improvements in skin and self-reported joint symptoms appeared to correlate. Patients with a PASI 50 to less-than PASI 75 response had a mean 17-point reduction in joint pain scores, while those with a PASI 75 to less-than PASI 90 response averaged a 25.1-point improvement in joint pain, patients with a PASI 90 to less-than PASI 100 skin response averaged a 27.6-point reduction, and PASI 100 responders had a mean 30.3-point reduction in joint pain scores.

“Obviously, one needs to look at this more carefully in a phase III psoriatic arthritis study. That’ll provide a more robust answer. But this gives a hint,” the dermatologist said.

The UNCOVER program was sponsored by Eli Lilly. Dr. Gottlieb serves as an adviser to Lilly and numerous other pharmaceutical companies.

[email protected]

COPENHAGEN – Ixekizumab not only shows considerable promise for the treatment of moderate to severe psoriasis, it looks like it may be a winner for comorbid psoriatic arthritis, too.

The investigational IgG4 humanized monoclonal antibody directed against interleukin-17A brought marked improvements in joint pain, systemic inflammatory burden, and quality of life as well as skin disease in patients with both psoriasis and self-reported psoriatic arthritis in a combined analysis of three phase III clinical trials, Dr. Alice B. Gottlieb reported at the annual congress of the European Academy of Dermatology and Venereology.

Of the 3,126 patients with moderate to severe psoriasis who participated in the 12-week, phase III UNCOVER-1, -2, and -3 trials, 751 (24%) also had self-reported psoriatic arthritis; her analysis focused on them.

She was quick to note that the UNCOVER trials were primarily psoriasis studies that relied upon patient self-report of psoriatic arthritis. Nevertheless, it seems likely that the great majority of self-reported psoriatic arthritis patients really did have the rheumatologic disease, since the mean baseline C-reactive protein (CRP) level in that group was 8.43 mg/L, a level far higher than expected in patients with psoriasis only.

In any case, more-rigorous phase III studies of ixekizumab conducted specifically in patients with formally rheumatologist-diagnosed psoriatic arthritis and treated in rheumatology practices are due to be presented at the annual meeting of the American College of Rheumatology in November. And while Dr. Gottlieb wasn’t at liberty to discuss those results, she did hint that the data will be strongly positive.

“If you’re happy about these UNCOVER findings, you’ll be ecstatic about those,” predicted Dr. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

Also coming up at the American College of Rheumatology meeting will be the results of the first-ever head-to-head comparison of an IL-17 inhibitor versus a tumor necrosis factor–alpha blocker in psoriatic arthritis patients. While at present most physicians consider a TNF inhibitor to be the treatment of choice in patients with psoriatic arthritis, that view may change as a result of the forthcoming comparative study, according to the dermatologist.

In each of the three phase III UNCOVER studies, patients were randomized to 12 weeks of subcutaneous ixekizumab at 80 mg every 2 or 4 weeks following a 160-mg loading dose, or to placebo. At baseline, the subgroup with self-reported psoriatic arthritis had a mean Psoriasis Area and Severity Index ( PASI) 0f about 21, a self-rated joint pain severity of 50 on a 0-100 scale, a CRP of 8.43 mg/L, and a Dermatology Life Quality Index (DLQI) score of 14.

Joint pain decreased dramatically in the two ixekizumab groups as early at 2 weeks into the trial, at which point, patients on treatment every 2 weeks averaged a 13.1-point reduction from baseline, with a similar 14.1-point drop noted in those on an every 4 weeks schedule. At week 12, the mean reductions from baseline were 25.2 and 26.8 points, compared with a 1.1-point increase in joint pain among placebo-treated controls.

Inflammatory burden plunged quickly, as evidenced by mean reductions in CRP of 4.63 mg/L and 4.33 mg/L at week 1 with biweekly and monthly dosing, respectively. These reductions were then maintained through week 12.

In terms of improvement in skin symptoms, with ixekizumab dosed every 2 weeks, the PASI 75 response was 89.8% at 12 weeks, the PASI 90 response was 69.3%, and the PASI 100 response (clear skin) was 37.1%. In patients treated every 4 weeks, the rates were 81.1%, 60.8%, and 34.7%.

“There’s good news in both groups, but I think the news is even better in the every-2-weeks group,” Dr. Gottlieb commented.

The mean 12-week decrease from baseline in DLQI was 11.8 points with biweekly dosing and 10.5 with 4-week dosing, compared with 0.8 points in controls. That’s impressive given that a 5-point reduction in DLQI is deemed clinically meaningful, the dermatologist observed. At 12 weeks, 56.5% of patients on ixekizumab every 2 weeks had a DLQI of 0 or 1, as did 54% on monthly dosing and 1.5% of controls.

The ixekizumab-treated groups also showed what Dr. Gottlieb described as “dramatic” improvements – in the 4+ to 5+ point range – in both the mental and physical component scores on the SF-36, another widely used quality of life measure.

Improvements in skin and self-reported joint symptoms appeared to correlate. Patients with a PASI 50 to less-than PASI 75 response had a mean 17-point reduction in joint pain scores, while those with a PASI 75 to less-than PASI 90 response averaged a 25.1-point improvement in joint pain, patients with a PASI 90 to less-than PASI 100 skin response averaged a 27.6-point reduction, and PASI 100 responders had a mean 30.3-point reduction in joint pain scores.

“Obviously, one needs to look at this more carefully in a phase III psoriatic arthritis study. That’ll provide a more robust answer. But this gives a hint,” the dermatologist said.

The UNCOVER program was sponsored by Eli Lilly. Dr. Gottlieb serves as an adviser to Lilly and numerous other pharmaceutical companies.

[email protected]