IL inhibitor options move psoriasis treatment forward

Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.

“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.

Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).

Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.

Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.

For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.

Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.

Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.

Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.

What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.

IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).

For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.

In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.

Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.

“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.

Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).

Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.

Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.

For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.

Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.

Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.

Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.

What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.

IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).

For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.

In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.

Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Psoriasis patients have many options, and more are on the way, according to J. Mark Jackson, MD, of the University of Louisville, Ky.

“Know the information regarding each [treatment] to best care for your patients,” Dr. Jackson said in a presentation at the annual Coastal Dermatology Symposium.

Dr. Jackson particularly addressed the interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, and secukinumab) and the IL-23 inhibitors (guselkumab, risankizumab, and tildrakizumab).

Complete clearance rates can reach 50% and higher over the long term when treating patients with IL-17 inhibitors, but patients must maintain regular dosing to maintain a response, he said.

Overall, comparisons of IL-17 inhibitors with etanercept, adalimumab, and ustekinumab “demonstrate better efficacy with no evidence of compromising safety,” he noted.

For example, secukinumab demonstrated significantly superior results when compared with ustekinumab in a randomized trial (J Am Acad Dermatol. 2015;73: 400-9). After 16 weeks of treatment, 79% of secukinumab patients achieved a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) versus 58% of ustekinumab patients, he said, and the drug safety profile was consistent with the pivotal phase 3 studies of secukinumab.

Concerns persist about increased risk of inflammatory bowel disease, Crohn’s disease, and ulcerative colitis in patients taking secukinumab and other IL-17 inhibitors, but data indicate that rates are low. The risk is low “and may be related to psoriasis and not the therapy,” he explained.

Ixekizumab has been associated with more injection site reactions than secukinumab, but these tend to be mild, Dr. Jackson said. Advantages of ixekizumab are that it works quickly and has demonstrated effectiveness against genital, palmoplantar, scalp, and nail psoriasis, he added.

Brodalumab also works quickly, but it has the unique inclusion of a Risk Evaluation and Mitigation Strategies (REMS) program because of suicidal ideation and behavior in clinical trials, he noted, adding that there are more data showing rates are low and the REMS program is easier to deal with than the isotretinoin REMS. The increased risk of superficial Staphylococcus and Candida infections are noted on IL-17 inhibitor labels, but this has not been a significant issue in trials or clinical practice, he said.

What is also exciting about the IL-17 inhibitors are the approvals of ixekizumab and secukinumab for patients with psoriatic arthritis (PsA), with both agents demonstrating the ability to inhibit the structural progression of joint damage over time, Dr. Jackson commented. These data seem to be on par with that of the TNF-inhibitors, although time will tell how this bears out clinically, he noted.

IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab (not yet approved) have shown similar effectiveness and are well tolerated by patients, with few injection site reactions or adverse events reported, Dr. Jackson said. The dosing regimens of each of these drugs, administered subcutaneously, are easy to follow: Treatment starts with an initial dose of either 100 mg (guselkumab and tildrakizumab) or 150 mg (risankizumab), which is followed by doses at 4 weeks and then doses every 8 weeks (guselkumab) or 12 weeks (tildrakizumab and risankizumab).

For example, in a comparison study of risankizumab with a dosage of 150 mg subcutaneously at week 0, 4, then every 12 weeks, 75% of risankizumab patients achieved PASI 90 at 16 weeks and 82% at 52 weeks, compared with 42% and 44%, respectively, for adalimumab patients.

In addition, the IL-23 inhibitors have demonstrated some benefits for PsA patients in clinical trials, but they are not currently indicated for PsA, he said.

Dr. Jackson disclosed having received research, honoraria, consulting, and/or other support from AbbVie, Accuitis, Aclaris, Celgene, Dr. Reddy’s, Galderma, Janssen, Lilly, Medimetriks, Novartis, Pfizer, Promius, Ralexar, Sienna, and TopMD.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.