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In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.
Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.
The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.
Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.
The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:
- Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
- Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
- The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
- Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
- Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
- None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
- No antibrodalumab antibodies were detected in any serum samples.
The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.
George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”
“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.
“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.
Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.
“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.
“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”
But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”
“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”
Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.
Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.
The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.
Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.
The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:
- Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
- Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
- The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
- Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
- Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
- None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
- No antibrodalumab antibodies were detected in any serum samples.
The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.
George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”
“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.
“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.
Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.
“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.
“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”
But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”
“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”
Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.
Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.
The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.
Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.
The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:
- Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
- Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
- The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
- Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
- Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
- None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
- No antibrodalumab antibodies were detected in any serum samples.
The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.
George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”
“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.
“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.
Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.
“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.
“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”
But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”
“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”
Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
FROM JAMA DERMATOLOGY