Article Type
Changed
Fri, 01/18/2019 - 18:05

 

Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. David Rosmarin of Tufts University, Boston
Bruce Jancin/MDedge News
Dr. David Rosmarin

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

 

 


Participants were an average of 33 years and had a disease duration of 12 years; 14 patients were Hurley Stage II, the rest Stage III. Their mean baseline DLQI was 12.

“Patients with hidradenitis suppurativa have a horrible quality of life,” Dr. Rosmarin commented. “When we compare it to patients who have atopic dermatitis, psoriasis, or chronic idiopathic urticaria, oftentimes patients with hidradenitis suppurativa suffer the worst and have the most quality of life impairment.”

Of the 18 patients, 14 – 7 of 9 in each group – achieved HiSCR. This included five of the six patients who were previous nonresponders to adalimumab or another anti-TNF biologic.



“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.



In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

Meeting/Event
Publications
Topics
Sections
Meeting/Event
Meeting/Event

 

Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. David Rosmarin of Tufts University, Boston
Bruce Jancin/MDedge News
Dr. David Rosmarin

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

 

 


Participants were an average of 33 years and had a disease duration of 12 years; 14 patients were Hurley Stage II, the rest Stage III. Their mean baseline DLQI was 12.

“Patients with hidradenitis suppurativa have a horrible quality of life,” Dr. Rosmarin commented. “When we compare it to patients who have atopic dermatitis, psoriasis, or chronic idiopathic urticaria, oftentimes patients with hidradenitis suppurativa suffer the worst and have the most quality of life impairment.”

Of the 18 patients, 14 – 7 of 9 in each group – achieved HiSCR. This included five of the six patients who were previous nonresponders to adalimumab or another anti-TNF biologic.



“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.



In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

 

Secukinumab racked up impressive results for the treatment of moderate to severe hidradenitis suppurativa in 18 patients in an open-label, proof-of-concept study, David Rosmarin, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. David Rosmarin of Tufts University, Boston
Bruce Jancin/MDedge News
Dr. David Rosmarin

“It was especially notable that secukinumab was effective in five of the six patients who had previously failed anti-TNF [tumor necrosis factor] therapy,” said Dr. Rosmarin, a dermatologist at Tufts University, Boston.

At present, the sole medication approved for treatment of hidradenitis suppurativa (HS) is the TNF inhibitor adalimumab (Humira). The rationale for investigating secukinumab (Cosentyx), a biologic that blocks the interleukin-17A receptor and is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, lies in the observation that HS lesions exhibit an increased ratio of Th17- to T-regulatory cells, compared with normal skin. Lesional skin also features elevated IL-17 levels. These abnormalities can be reversed by anti-TNF therapy, he explained.

Dr. Rosmarin presented a 28-week, open-label study in which 18 patients with moderate to severe HS received an induction regimen consisting of 300 mg secukinumab given subcutaneously once weekly for 5 weeks and were then randomized to the same dose of the biologic given either every 2 or 4 weeks until week 24.

The primary endpoint was achievement of a Hidradenitis Suppurativa Clinical Response (HiSCR) at 24 weeks. This requires no increase in the number of draining fistulae or abscesses, compared with baseline, plus at least a 50% reduction in total inflammatory nodules. Secondary endpoints were the mean change from baseline in the Sartorius Scale as well as on the Dermatology Life Quality Index (DLQI).

 

 


Participants were an average of 33 years and had a disease duration of 12 years; 14 patients were Hurley Stage II, the rest Stage III. Their mean baseline DLQI was 12.

“Patients with hidradenitis suppurativa have a horrible quality of life,” Dr. Rosmarin commented. “When we compare it to patients who have atopic dermatitis, psoriasis, or chronic idiopathic urticaria, oftentimes patients with hidradenitis suppurativa suffer the worst and have the most quality of life impairment.”

Of the 18 patients, 14 – 7 of 9 in each group – achieved HiSCR. This included five of the six patients who were previous nonresponders to adalimumab or another anti-TNF biologic.



“The other thing we noticed was the rapidity of response, which is important to a lot of our patients. It took an average of 7 weeks to achieve HiSCR, and eight patients achieved HiSCR during the induction phase of treatment,” the dermatologist said.

Mean scores on the Sartorius Scale dropped by 28%. Similarly, scores on the DLQI improved by a mean of 3.6 points, or 26%. Nine patients experienced a reduction of 5 points or more on the DLQI. “This happened largely in the first 1-2 months of therapy,” Dr. Rosmarin continued.

Secukinumab was well tolerated. There were no treatment discontinuations because of adverse events. Four patients, all in the biweekly dosing arm, developed Candida infections, all easily cured using topical ketoconazole.

The next step will be to conduct a large, placebo-controlled, randomized trial to firmly establish the efficacy of secukinumab for HS. Also, the optimal dosing of the biologic for induction and long-term maintenance therapy have yet to be determined. Over the long term, it will be important to see whether marked improvement in HS is accompanied by a reduction in the elevated cardiovascular risk associated with this inflammatory disease, he added.



In 2019, a trial will get underway to compare two doses of secukinumab for patients with HS. Based on a search of clinical trials at ClinicalTrials.gov, a wide range of monoclonal antibody therapies are being investigated for the treatment of HS.

The results of this preliminary study of secukinumab emphasize the importance of the Th17 pathway in HS and open the door to alternative strategies targeting this pathway. Dr. Rosmarin noted that he and his coinvestigators have collected a case series of positive responses to guselkumab (Tremfya), which targets the IL-23 p19 subunit, which also lies along the Th17 pathway.

The secukinumab study was sponsored by Novartis. Dr. Rosmarin reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

Publications
Publications
Topics
Article Type
Click for Credit Status
Ready
Sections
Article Source

REPORTING FROM THE EADV CONGRESS

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Vitals

 

Key clinical point: Secukinumab shows considerable promise for treatment of hidradenitis suppurativa.

Major finding: Hidradenitis suppurativa improved markedly in response to secukinumab in 14 of 18 patients.

Study details: This prospective, open-label, 28-week study included 18 patients with hidradenitis suppurativa who were randomized to one of two secukinumab dosing regimens.

Disclosures: The study was sponsored by Novartis. The presenter reported serving as a consultant to or on speakers’ bureaus for that company and more than half a dozen other pharmaceutical companies.

Disqus Comments
Default
Use ProPublica