Conference Coverage

For pain related to skin disorders, dermatologists should generally consider management as their direct responsibility without referrals, according to an expert who outlined his strategies at the American Academy of Dermatology Virtual Meeting Experience.

The exceptions relate primarily to patients with issues complicating pain control, such as those with psychosocial problems exacerbating the pain response, drug-seeking behavior, or both, according to Robert G. Micheletti, MD, chief of hospital dermatology, University of Pennsylvania, Philadelphia.

To stay out of trouble, Dr. Micheletti advocated a systematic approach to the control of pain that includes documentation, clear expectations, and a sparing use of opioids only at the lowest acceptable dose for periods measured in days.

Using a case of pyoderma gangrenosum to make several points, he recognized that some patients do have a level of pain that warrants a short course of opioids, but this is not his first step. Rather, the initial focus, after administering standard therapies for this disease, is wound care, which often attenuates symptoms. He adds non-pharmacologic treatments, such as ice, heat, and rest when appropriate. The initial pharmacologic approach is alternating doses of an NSAID and acetaminophen.

“If necessary, a short course of opioids is reasonable for patients with acute pain,” he acknowledged. But he wants to avoid providing more opioids than needed to address the initial period of acute pain. In the case of pyoderma gangrenosum, he suggested a typical prescription might be 12 pills of 5 mg oxycodone taken every six hours. A followup appointment within a week provides the opportunity to reassess.

“Set clear expectations,” Dr. Micheletti said. This includes explaining that the goal is manageable pain, not complete pain relief, which is often unobtainable. For painful conditions such as pyoderma gangrenosum, hidradenitis suppurativa, or vasculitis, a short course will generally be sufficient to get past the most significant discomfort.

There are several reasons that Dr. Micheletti encourages dermatologists to take responsibility for pain related to skin diseases. One is the potential for inefficiencies and delays common to referrals, but another is the value of the dermatologist’s expertise in judging pain as a symptom of the disorder. With effective treatment, pain should self-resolve.

“If the patient is not getting better medically, then change therapies,” Dr. Micheletti said. When referred to a non-dermatologist, the pain expert might not recognize what persistent pain is revealing about the underlying condition.

Repeatedly, Dr. Micheletti made the point that dermatologists should manage pain related to skin disorders because of their ability to assess complaints in the context of the disease.

“We are the experts. We should understand when what we are seeing should or should not be painful,” he said. He added that dermatologists are also in the best position to judge “when analgesia is no longer needed.”

With this same logic, dermatologists are in a good position to distinguish nociceptive from neuropathic pain. Some conditions are likely to have both, and this should influence choice of pain relief. Citing a patient with calciphylaxis as an example, Dr. Micheletti suggested that drugs with efficacy against neuropathic pain, such as gabapentin, should be one of the options to consider before moving to opioids. In those with sufficient pain to warrant an opioid, however, Dr. Micheletti would consider tramadol, which acts on both types of pain.

Treating pain is not always straightforward, Dr. Micheletti acknowledged. For example, depression and mood disorders are known to exacerbate pain and are reasonable targets of pain control. The stress related to disruptive psychosocial problems can be another factor in risk of pain.

“Be prepared to acknowledge and address these types of issues,” Dr. Micheletti said. Although these are the types of patients some dermatologists might prefer to refer to a pain specialist, he said that the contribution of factors outside of skin disease should not be allowed to obscure a dermatologic source of pain.

“Just because a patient has psychosocial issues does not mean that there is no pain,” he said.

A systematic approach to the assessment and treatment of pain will help sort out these issues, but Dr. Micheletti also said, “Know your comfort zone.” When patients require opioids, there are several appropriate steps important or mandatory to provide adequate protection for the patient and the physician. In addition to documentation, it is reasonable to verify that the patient is not obtaining opioids from other prescribers, a step that is mandatory in some states.

When opioids are needed, Dr. Micheletti suggested a standard approach that includes short courses without refills. He recommended avoiding long-acting opioids and drugs not commonly used by non-pain specialists, such as codeine, hydrocodone, or fentanyl.

“This is not a prescribe and walk away situation,” he said.

Although the same general approach is employed by Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, he is a little less reluctant to refer patients to pain specialists.

“For complex situations, you need complex solutions. In the case of significant pain and even itch, I will collaborate with the GW Pain Center,” he said. For severe pain, the solutions might include nerve blocks or even intravenous ketamine for in-patients.

He also made the point that dermatologists, even if they are uncomfortable prescribing opioids, “should be equipped to use relevant medications such as topical anesthetics, gabapentinoids, and SSRIs” to control pain related to skin conditions.

Dr. Micheletti reports no relevant conflicts of interest. Dr. Friedman has consulting relationships with several pharmaceutical companies, including Amgen, GlaxoSmithKline, and Valeant.

For pain related to skin disorders, dermatologists should generally consider management as their direct responsibility without referrals, according to an expert who outlined his strategies at the American Academy of Dermatology Virtual Meeting Experience.

The exceptions relate primarily to patients with issues complicating pain control, such as those with psychosocial problems exacerbating the pain response, drug-seeking behavior, or both, according to Robert G. Micheletti, MD, chief of hospital dermatology, University of Pennsylvania, Philadelphia.

To stay out of trouble, Dr. Micheletti advocated a systematic approach to the control of pain that includes documentation, clear expectations, and a sparing use of opioids only at the lowest acceptable dose for periods measured in days.

Using a case of pyoderma gangrenosum to make several points, he recognized that some patients do have a level of pain that warrants a short course of opioids, but this is not his first step. Rather, the initial focus, after administering standard therapies for this disease, is wound care, which often attenuates symptoms. He adds non-pharmacologic treatments, such as ice, heat, and rest when appropriate. The initial pharmacologic approach is alternating doses of an NSAID and acetaminophen.

“If necessary, a short course of opioids is reasonable for patients with acute pain,” he acknowledged. But he wants to avoid providing more opioids than needed to address the initial period of acute pain. In the case of pyoderma gangrenosum, he suggested a typical prescription might be 12 pills of 5 mg oxycodone taken every six hours. A followup appointment within a week provides the opportunity to reassess.

“Set clear expectations,” Dr. Micheletti said. This includes explaining that the goal is manageable pain, not complete pain relief, which is often unobtainable. For painful conditions such as pyoderma gangrenosum, hidradenitis suppurativa, or vasculitis, a short course will generally be sufficient to get past the most significant discomfort.

There are several reasons that Dr. Micheletti encourages dermatologists to take responsibility for pain related to skin diseases. One is the potential for inefficiencies and delays common to referrals, but another is the value of the dermatologist’s expertise in judging pain as a symptom of the disorder. With effective treatment, pain should self-resolve.

“If the patient is not getting better medically, then change therapies,” Dr. Micheletti said. When referred to a non-dermatologist, the pain expert might not recognize what persistent pain is revealing about the underlying condition.

Repeatedly, Dr. Micheletti made the point that dermatologists should manage pain related to skin disorders because of their ability to assess complaints in the context of the disease.

“We are the experts. We should understand when what we are seeing should or should not be painful,” he said. He added that dermatologists are also in the best position to judge “when analgesia is no longer needed.”

With this same logic, dermatologists are in a good position to distinguish nociceptive from neuropathic pain. Some conditions are likely to have both, and this should influence choice of pain relief. Citing a patient with calciphylaxis as an example, Dr. Micheletti suggested that drugs with efficacy against neuropathic pain, such as gabapentin, should be one of the options to consider before moving to opioids. In those with sufficient pain to warrant an opioid, however, Dr. Micheletti would consider tramadol, which acts on both types of pain.

Treating pain is not always straightforward, Dr. Micheletti acknowledged. For example, depression and mood disorders are known to exacerbate pain and are reasonable targets of pain control. The stress related to disruptive psychosocial problems can be another factor in risk of pain.

“Be prepared to acknowledge and address these types of issues,” Dr. Micheletti said. Although these are the types of patients some dermatologists might prefer to refer to a pain specialist, he said that the contribution of factors outside of skin disease should not be allowed to obscure a dermatologic source of pain.

“Just because a patient has psychosocial issues does not mean that there is no pain,” he said.

A systematic approach to the assessment and treatment of pain will help sort out these issues, but Dr. Micheletti also said, “Know your comfort zone.” When patients require opioids, there are several appropriate steps important or mandatory to provide adequate protection for the patient and the physician. In addition to documentation, it is reasonable to verify that the patient is not obtaining opioids from other prescribers, a step that is mandatory in some states.

When opioids are needed, Dr. Micheletti suggested a standard approach that includes short courses without refills. He recommended avoiding long-acting opioids and drugs not commonly used by non-pain specialists, such as codeine, hydrocodone, or fentanyl.

“This is not a prescribe and walk away situation,” he said.

Although the same general approach is employed by Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, he is a little less reluctant to refer patients to pain specialists.

“For complex situations, you need complex solutions. In the case of significant pain and even itch, I will collaborate with the GW Pain Center,” he said. For severe pain, the solutions might include nerve blocks or even intravenous ketamine for in-patients.

He also made the point that dermatologists, even if they are uncomfortable prescribing opioids, “should be equipped to use relevant medications such as topical anesthetics, gabapentinoids, and SSRIs” to control pain related to skin conditions.

Dr. Micheletti reports no relevant conflicts of interest. Dr. Friedman has consulting relationships with several pharmaceutical companies, including Amgen, GlaxoSmithKline, and Valeant.

For pain related to skin disorders, dermatologists should generally consider management as their direct responsibility without referrals, according to an expert who outlined his strategies at the American Academy of Dermatology Virtual Meeting Experience.

The exceptions relate primarily to patients with issues complicating pain control, such as those with psychosocial problems exacerbating the pain response, drug-seeking behavior, or both, according to Robert G. Micheletti, MD, chief of hospital dermatology, University of Pennsylvania, Philadelphia.

To stay out of trouble, Dr. Micheletti advocated a systematic approach to the control of pain that includes documentation, clear expectations, and a sparing use of opioids only at the lowest acceptable dose for periods measured in days.

Using a case of pyoderma gangrenosum to make several points, he recognized that some patients do have a level of pain that warrants a short course of opioids, but this is not his first step. Rather, the initial focus, after administering standard therapies for this disease, is wound care, which often attenuates symptoms. He adds non-pharmacologic treatments, such as ice, heat, and rest when appropriate. The initial pharmacologic approach is alternating doses of an NSAID and acetaminophen.

“If necessary, a short course of opioids is reasonable for patients with acute pain,” he acknowledged. But he wants to avoid providing more opioids than needed to address the initial period of acute pain. In the case of pyoderma gangrenosum, he suggested a typical prescription might be 12 pills of 5 mg oxycodone taken every six hours. A followup appointment within a week provides the opportunity to reassess.

“Set clear expectations,” Dr. Micheletti said. This includes explaining that the goal is manageable pain, not complete pain relief, which is often unobtainable. For painful conditions such as pyoderma gangrenosum, hidradenitis suppurativa, or vasculitis, a short course will generally be sufficient to get past the most significant discomfort.

There are several reasons that Dr. Micheletti encourages dermatologists to take responsibility for pain related to skin diseases. One is the potential for inefficiencies and delays common to referrals, but another is the value of the dermatologist’s expertise in judging pain as a symptom of the disorder. With effective treatment, pain should self-resolve.

“If the patient is not getting better medically, then change therapies,” Dr. Micheletti said. When referred to a non-dermatologist, the pain expert might not recognize what persistent pain is revealing about the underlying condition.

Repeatedly, Dr. Micheletti made the point that dermatologists should manage pain related to skin disorders because of their ability to assess complaints in the context of the disease.

“We are the experts. We should understand when what we are seeing should or should not be painful,” he said. He added that dermatologists are also in the best position to judge “when analgesia is no longer needed.”

With this same logic, dermatologists are in a good position to distinguish nociceptive from neuropathic pain. Some conditions are likely to have both, and this should influence choice of pain relief. Citing a patient with calciphylaxis as an example, Dr. Micheletti suggested that drugs with efficacy against neuropathic pain, such as gabapentin, should be one of the options to consider before moving to opioids. In those with sufficient pain to warrant an opioid, however, Dr. Micheletti would consider tramadol, which acts on both types of pain.

Treating pain is not always straightforward, Dr. Micheletti acknowledged. For example, depression and mood disorders are known to exacerbate pain and are reasonable targets of pain control. The stress related to disruptive psychosocial problems can be another factor in risk of pain.

“Be prepared to acknowledge and address these types of issues,” Dr. Micheletti said. Although these are the types of patients some dermatologists might prefer to refer to a pain specialist, he said that the contribution of factors outside of skin disease should not be allowed to obscure a dermatologic source of pain.

“Just because a patient has psychosocial issues does not mean that there is no pain,” he said.

A systematic approach to the assessment and treatment of pain will help sort out these issues, but Dr. Micheletti also said, “Know your comfort zone.” When patients require opioids, there are several appropriate steps important or mandatory to provide adequate protection for the patient and the physician. In addition to documentation, it is reasonable to verify that the patient is not obtaining opioids from other prescribers, a step that is mandatory in some states.

When opioids are needed, Dr. Micheletti suggested a standard approach that includes short courses without refills. He recommended avoiding long-acting opioids and drugs not commonly used by non-pain specialists, such as codeine, hydrocodone, or fentanyl.

“This is not a prescribe and walk away situation,” he said.

Although the same general approach is employed by Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, he is a little less reluctant to refer patients to pain specialists.

“For complex situations, you need complex solutions. In the case of significant pain and even itch, I will collaborate with the GW Pain Center,” he said. For severe pain, the solutions might include nerve blocks or even intravenous ketamine for in-patients.

He also made the point that dermatologists, even if they are uncomfortable prescribing opioids, “should be equipped to use relevant medications such as topical anesthetics, gabapentinoids, and SSRIs” to control pain related to skin conditions.

Dr. Micheletti reports no relevant conflicts of interest. Dr. Friedman has consulting relationships with several pharmaceutical companies, including Amgen, GlaxoSmithKline, and Valeant.

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

A version of this article first appeared on Medscape.com.

Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

A version of this article first appeared on Medscape.com.

Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

A version of this article first appeared on Medscape.com.

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

A version of this article first appeared on Medscape.com.

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

A version of this article first appeared on Medscape.com.

Intranasal zavegepant, a third-generation calcitonin gene-related peptide (CGRP) receptor agonist, is effective and well tolerated in the treatment of acute migraine, new research shows. In a randomized dose-ranging, placebo-controlled, phase 2/3 trial, investigators found both the 10- and 20-mg doses of the drug were associated with pain freedom in more than 20% of patients and alleviated the most bothersome symptom, defined as photophobia, phonophobia, or nausea, in more than 40% of patients.

Most adverse events associated with zavegepant were mild or moderate. The drug is not associated with liver toxicity.

Three doses

Zavegepant is the only intranasal CGRP receptor antagonist undergoing late-stage development for the acute treatment of migraine. A previous single ascending dose study suggested the drug provided systemic exposure and had potentially therapeutic effects.

The study included participants age 18 years or older who had a diagnosis of migraine for at least 1 year, had two to eight migraine attacks of moderate or severe intensity and fewer than 15 monthly headache days over the previous 3 months.

The investigators randomly assigned participants in this phase 2/3 trial to placebo or a 5-mg, 10-mg, or 20-mg dose of intranasal zavegepant. Participants treated a single attack of moderate to severe pain with their assigned treatment.

The study’s two primary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours after dosing.

The investigators randomly assigned 1,673 participants to treatment. Of this group, 1,588 treated an attack with study medication. The researchers also included 1,581 participants in the modified intention-to-treat population. Of this group, 387 received the 5-mg dose, 391 received the 10-mg dose, 402 received the 20-mg dose, and 401 received placebo.
 

Pain freedom

The population’s median age was approximately 41 years, 86% of participants were female, and 14% were taking preventive migraine medication. Participants’ mean number of moderate or severe attacks per month was 4.9 overall. The most common most bothersome symptom was photophobia.

The researchers observed a difference in outcome between the active and placebo arms as early as 15 minutes post-dose, but this difference was not statistically significant. At 2 hours, the rate of pain freedom was 15.5% in the placebo group, 22.5% in the 10-mg group (P = .0113), and 23.1% in the 20-mg group (P = .0055). The result for the 5-mg group (19.6%) was not significantly different from that of the placebo group.

The rate of freedom from the most bothersome symptom was 33.7% in the placebo group, 41.9% in the 10-mg group (P = .0155), and 42.5% in the 20-mg group (P = .0094). For this endpoint as well, the result of the 5-mg group (39%) was not significantly different from that among controls.

The most common adverse events were dysgeusia (impaired sense of taste) and nasal discomfort. The rate of dysgeusia ranged from 13.5% to 16.1% in the zavegepant groups, compared with 3.5% among controls. The rate of nasal discomfort ranged from 1.3% to 5.2% in the zavegepant groups, compared with 0.2% among controls. The investigators concluded that intranasal zavegepant had a favorable safety profile.
 

‘Exciting potential addition’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said: “Zavegepant is an exciting potential addition to rimegepant for the acute care of migraine.”

Many patients like the orally dissolving tablet formulation of rimegepant (Nurtec), but some have nausea and do not absorb oral preparations well, said Dr. Rapoport, who is editor-in-chief of Neurology Reviews and a past president of the International Headache Society. “So, it makes sense to have a gepant, which is not a vasoconstrictor and has few adverse events, developed as a nasal spray.” Nasal preparations often work more quickly than oral preparations, he added.

Other intranasal treatments available for migraine include dihydroergotamine (Migranal), zolmitriptan (Zomig), sumatriptan (Imitrex), and ketorolac (Sprix). It is not possible to compare zavegepant with these medications, or with other CGRP receptor antagonists, because they have not been studied in head-to-head trials, said Dr. Rapoport, who was not involved in the study but has previously consulted for Biohaven Pharmaceuticals, the drug’s manufacturer.

“I would predict a nasal spray would work somewhat faster and better in some patients with nausea or poor absorption, so I would be happy to have it approved and available.”

The current study uses endpoints typically prescribed by the U.S. Food and Drug Administration and includes a large sample size, said Dr. Rapoport.

“During the informed consent [stage], the patients in this trial would be told that there is a 3-in-4 chance that they would be getting an active drug versus placebo, and that often increases the placebo response,” he added. “In this trial, a placebo response of 15.5% is slightly high, but not atypical,” he added.

This study raises the question of whether other acute-care migraine medications should be studied as nasal preparations. “I think the answer is yes,” said Dr. Rapoport. “Fast-acting, effective nasal preparations that are easy to use and cause few adverse events [are] what we need.”

Biohaven Pharmaceuticals sponsored the study. Dr. Lipton has been a consultant for Biohaven, has conducted studies funded by the company, and has stock in the company. Dr. Rapoport has consulted and spoken for Biohaven, but did not participate in the current study.

A version of this article first appeared on Medscape.com.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

Hispanic diabetes patients are significantly less likely than Black or White patients to receive preventive guideline-based care soon after diagnosis, based on data from more than 7,000 individuals.

Racial and ethnic disparities in diabetes care remain a pervasive health problem, and minorities including non-Hispanic Blacks and Hispanics experience higher rates of complications, including retinopathy and neuropathy, compared with other groups, Felippe Ottoni Marcondes, MD, of Massachusetts General Hospital, Boston, and colleagues noted in a poster presented at the annual meeting of the Society for General Internal Medicine.

Data from previous studies have shown that diabetes patients who receive guideline-directed preventive care soon after diagnosis can reduce their risk of complications, they said.

To identify disparities in the provision of guideline-directed preventive care, the researchers analyzed data from 7,341 individuals who participated in the National Health Interview Survey from 2011 to 2017. They reviewed associations between race/ethnicity and visits to an eye specialist, a foot specialist, and checks of blood pressure and cholesterol in the past year among individuals diagnosed with diabetes within the past 5 years.

Overall, Hispanics had significantly lower rates of insurance coverage (75.9%), compared with non-Hispanic Whites (93.2%) and non-Hispanic Blacks (88.1%; P < .001).

Hispanics also were significantly less likely than Whites to have had a prior year eye exam (odds ratio, 0.80) and blood pressure check (OR, 0.45), after controlling for variables including age, sex, socioeconomic status, health insurance, general health status, U.S. region, marital status, body mass index, and various comorbidities.

Although insurance coverage mediated 42.8% of the total effect of race/ethnicity on annual eye specialist visits for Hispanics as compared with Whites, there was no significant effect for Blacks, compared with Whites.
 

COVID concerns impact diabetes disparities

“As the diabetes epidemic continues in the U.S., it is important to bring to the front of the diabetes care conversation racial/ethnic disparities that persisted or have been only partially addressed,” Dr. Marcondes said in an interview. “It is also important to emphasize that patients with diabetes are at higher risk for COVID-19 hospitalizations, complications, and death, and COVID-19 has disproportionately affected racial/ethnic minorities, so racial/ethnic minorities with diabetes have compounded risk of complications not only from diabetes but also from COVID-19.

“Importantly, our study highlights disparities in health care that are likely the product of systemic inequalities in access to care and insurance coverage at a moment when conversations about the race/racism and their health impact are fresh in the minds of public and health policy officials and the general public,” he emphasized.

“Unfortunately, I cannot say that I am surprised by our findings,” Dr. Marcondes said. “We expected to see some differences in the receipt of care for racial/ethnic minorities compared to white individuals for those recently diagnosed with diabetes, and that is exactly what our findings show.”

However, “what was perhaps intriguing is that disparities in the receipt of guideline-directed care were greater for Hispanic compared to White individuals than for Black compared to White individuals,” said Dr. Marcondes. “The causes of these differences are many. Hispanic individuals are less likely than White and Black persons to have insurance coverage.” Other unmeasured factors include language barriers that Hispanic individuals may face, as well as the bias and discrimination experienced by Hispanic and Black individuals alike.
 

Focus on equitable early intervention

“There is plenty of evidence in the medical literature that Black and Hispanic individuals with diabetes, as well as other minorities, have higher risk of complications of diabetes such as retinopathy, nephropathy, as well as cardiovascular risk factors such as high blood pressure and cholesterol,” Dr. Marcondes said. “Yet, complications in the time that immediately follows the diagnosis of diabetes are likely to be low.”

To reduce the risk of complications in the future, “physicians and health providers need to focus on providing equitable, guideline-directed treatment for their minority patients recently diagnosed with diabetes,” Dr. Marcondes emphasized. “Intervening early in the disease course will hopefully lead to a decrease in the rate of complications for racial/ethnic minorities. Clinicians, especially primary care physicians and providers, need to be aware that they are often the first encounter of many patients with the health care system. Effective communication and unbiased language on the part of clinicians will lead to stronger patient-physician relationships that foster opportunity to discuss disease prevention.

“Additional research is needed to evaluate the attitudes and biases of primary care providers and access the impact of patient navigation resources when treating minority patients with diabetes,” he concluded.

Digging Deeper into Disparities
“In diabetes, there are known racial and ethnic disparities such that minorities receive suboptimal screening and treatment, and have worse outcomes,” said Scott J. Pilla, MD, of The Johns Hopkins University School of Medicine, Baltimore, in an interview. 

“This study examines disparities in diabetes preventive measures in the U.S. using a national survey (NHIS) over the past decade. They took the important step of stratifying their analyses by health insurance and socioeconomic status which, in addition to race, may have a large impact,” said Dr. Pilla. However, “One critique of the poster is that it is unclear whether the researchers weighted their analyses to account for the nationally representative sampling of the NHIS survey,” he noted. 
Dr. Pilla said the finding that Hispanic patients had fewer diabetes preventive measures lines up with previous research in this area. 

“I was surprised that the disparities did not extend to black patients, who have been found to also receive suboptimal care compared to white patients in other studies,” he noted. 

The message for clinical practice: “Minorities with diabetes are at a higher risk of adverse diabetes outcomes and may need extra support and resources to achieve their evidence-based diabetes prevention,” Dr. Pilla said. 

“More research is needed to understand the root cause of racial and ethnic disparities in diabetes management to tease apart possible contributors including health insurance coverage, socioeconomic factors, cultural and community factors, and systemic racism. This will help inform targeted approaches to reducing disparities in diabetes care,” he emphasized.

The researchers had no relevant financial conflicts to disclose. Dr. Pilla had no financial conflicts to disclose. 

Hispanic diabetes patients are significantly less likely than Black or White patients to receive preventive guideline-based care soon after diagnosis, based on data from more than 7,000 individuals.

Racial and ethnic disparities in diabetes care remain a pervasive health problem, and minorities including non-Hispanic Blacks and Hispanics experience higher rates of complications, including retinopathy and neuropathy, compared with other groups, Felippe Ottoni Marcondes, MD, of Massachusetts General Hospital, Boston, and colleagues noted in a poster presented at the annual meeting of the Society for General Internal Medicine.

Data from previous studies have shown that diabetes patients who receive guideline-directed preventive care soon after diagnosis can reduce their risk of complications, they said.

To identify disparities in the provision of guideline-directed preventive care, the researchers analyzed data from 7,341 individuals who participated in the National Health Interview Survey from 2011 to 2017. They reviewed associations between race/ethnicity and visits to an eye specialist, a foot specialist, and checks of blood pressure and cholesterol in the past year among individuals diagnosed with diabetes within the past 5 years.

Overall, Hispanics had significantly lower rates of insurance coverage (75.9%), compared with non-Hispanic Whites (93.2%) and non-Hispanic Blacks (88.1%; P < .001).

Hispanics also were significantly less likely than Whites to have had a prior year eye exam (odds ratio, 0.80) and blood pressure check (OR, 0.45), after controlling for variables including age, sex, socioeconomic status, health insurance, general health status, U.S. region, marital status, body mass index, and various comorbidities.

Although insurance coverage mediated 42.8% of the total effect of race/ethnicity on annual eye specialist visits for Hispanics as compared with Whites, there was no significant effect for Blacks, compared with Whites.
 

COVID concerns impact diabetes disparities

“As the diabetes epidemic continues in the U.S., it is important to bring to the front of the diabetes care conversation racial/ethnic disparities that persisted or have been only partially addressed,” Dr. Marcondes said in an interview. “It is also important to emphasize that patients with diabetes are at higher risk for COVID-19 hospitalizations, complications, and death, and COVID-19 has disproportionately affected racial/ethnic minorities, so racial/ethnic minorities with diabetes have compounded risk of complications not only from diabetes but also from COVID-19.

“Importantly, our study highlights disparities in health care that are likely the product of systemic inequalities in access to care and insurance coverage at a moment when conversations about the race/racism and their health impact are fresh in the minds of public and health policy officials and the general public,” he emphasized.

“Unfortunately, I cannot say that I am surprised by our findings,” Dr. Marcondes said. “We expected to see some differences in the receipt of care for racial/ethnic minorities compared to white individuals for those recently diagnosed with diabetes, and that is exactly what our findings show.”

However, “what was perhaps intriguing is that disparities in the receipt of guideline-directed care were greater for Hispanic compared to White individuals than for Black compared to White individuals,” said Dr. Marcondes. “The causes of these differences are many. Hispanic individuals are less likely than White and Black persons to have insurance coverage.” Other unmeasured factors include language barriers that Hispanic individuals may face, as well as the bias and discrimination experienced by Hispanic and Black individuals alike.
 

Focus on equitable early intervention

“There is plenty of evidence in the medical literature that Black and Hispanic individuals with diabetes, as well as other minorities, have higher risk of complications of diabetes such as retinopathy, nephropathy, as well as cardiovascular risk factors such as high blood pressure and cholesterol,” Dr. Marcondes said. “Yet, complications in the time that immediately follows the diagnosis of diabetes are likely to be low.”

To reduce the risk of complications in the future, “physicians and health providers need to focus on providing equitable, guideline-directed treatment for their minority patients recently diagnosed with diabetes,” Dr. Marcondes emphasized. “Intervening early in the disease course will hopefully lead to a decrease in the rate of complications for racial/ethnic minorities. Clinicians, especially primary care physicians and providers, need to be aware that they are often the first encounter of many patients with the health care system. Effective communication and unbiased language on the part of clinicians will lead to stronger patient-physician relationships that foster opportunity to discuss disease prevention.

“Additional research is needed to evaluate the attitudes and biases of primary care providers and access the impact of patient navigation resources when treating minority patients with diabetes,” he concluded.

Digging Deeper into Disparities
“In diabetes, there are known racial and ethnic disparities such that minorities receive suboptimal screening and treatment, and have worse outcomes,” said Scott J. Pilla, MD, of The Johns Hopkins University School of Medicine, Baltimore, in an interview. 

“This study examines disparities in diabetes preventive measures in the U.S. using a national survey (NHIS) over the past decade. They took the important step of stratifying their analyses by health insurance and socioeconomic status which, in addition to race, may have a large impact,” said Dr. Pilla. However, “One critique of the poster is that it is unclear whether the researchers weighted their analyses to account for the nationally representative sampling of the NHIS survey,” he noted. 
Dr. Pilla said the finding that Hispanic patients had fewer diabetes preventive measures lines up with previous research in this area. 

“I was surprised that the disparities did not extend to black patients, who have been found to also receive suboptimal care compared to white patients in other studies,” he noted. 

The message for clinical practice: “Minorities with diabetes are at a higher risk of adverse diabetes outcomes and may need extra support and resources to achieve their evidence-based diabetes prevention,” Dr. Pilla said. 

“More research is needed to understand the root cause of racial and ethnic disparities in diabetes management to tease apart possible contributors including health insurance coverage, socioeconomic factors, cultural and community factors, and systemic racism. This will help inform targeted approaches to reducing disparities in diabetes care,” he emphasized.

The researchers had no relevant financial conflicts to disclose. Dr. Pilla had no financial conflicts to disclose. 

Hispanic diabetes patients are significantly less likely than Black or White patients to receive preventive guideline-based care soon after diagnosis, based on data from more than 7,000 individuals.

Racial and ethnic disparities in diabetes care remain a pervasive health problem, and minorities including non-Hispanic Blacks and Hispanics experience higher rates of complications, including retinopathy and neuropathy, compared with other groups, Felippe Ottoni Marcondes, MD, of Massachusetts General Hospital, Boston, and colleagues noted in a poster presented at the annual meeting of the Society for General Internal Medicine.

Data from previous studies have shown that diabetes patients who receive guideline-directed preventive care soon after diagnosis can reduce their risk of complications, they said.

To identify disparities in the provision of guideline-directed preventive care, the researchers analyzed data from 7,341 individuals who participated in the National Health Interview Survey from 2011 to 2017. They reviewed associations between race/ethnicity and visits to an eye specialist, a foot specialist, and checks of blood pressure and cholesterol in the past year among individuals diagnosed with diabetes within the past 5 years.

Overall, Hispanics had significantly lower rates of insurance coverage (75.9%), compared with non-Hispanic Whites (93.2%) and non-Hispanic Blacks (88.1%; P < .001).

Hispanics also were significantly less likely than Whites to have had a prior year eye exam (odds ratio, 0.80) and blood pressure check (OR, 0.45), after controlling for variables including age, sex, socioeconomic status, health insurance, general health status, U.S. region, marital status, body mass index, and various comorbidities.

Although insurance coverage mediated 42.8% of the total effect of race/ethnicity on annual eye specialist visits for Hispanics as compared with Whites, there was no significant effect for Blacks, compared with Whites.
 

COVID concerns impact diabetes disparities

“As the diabetes epidemic continues in the U.S., it is important to bring to the front of the diabetes care conversation racial/ethnic disparities that persisted or have been only partially addressed,” Dr. Marcondes said in an interview. “It is also important to emphasize that patients with diabetes are at higher risk for COVID-19 hospitalizations, complications, and death, and COVID-19 has disproportionately affected racial/ethnic minorities, so racial/ethnic minorities with diabetes have compounded risk of complications not only from diabetes but also from COVID-19.

“Importantly, our study highlights disparities in health care that are likely the product of systemic inequalities in access to care and insurance coverage at a moment when conversations about the race/racism and their health impact are fresh in the minds of public and health policy officials and the general public,” he emphasized.

“Unfortunately, I cannot say that I am surprised by our findings,” Dr. Marcondes said. “We expected to see some differences in the receipt of care for racial/ethnic minorities compared to white individuals for those recently diagnosed with diabetes, and that is exactly what our findings show.”

However, “what was perhaps intriguing is that disparities in the receipt of guideline-directed care were greater for Hispanic compared to White individuals than for Black compared to White individuals,” said Dr. Marcondes. “The causes of these differences are many. Hispanic individuals are less likely than White and Black persons to have insurance coverage.” Other unmeasured factors include language barriers that Hispanic individuals may face, as well as the bias and discrimination experienced by Hispanic and Black individuals alike.
 

Focus on equitable early intervention

“There is plenty of evidence in the medical literature that Black and Hispanic individuals with diabetes, as well as other minorities, have higher risk of complications of diabetes such as retinopathy, nephropathy, as well as cardiovascular risk factors such as high blood pressure and cholesterol,” Dr. Marcondes said. “Yet, complications in the time that immediately follows the diagnosis of diabetes are likely to be low.”

To reduce the risk of complications in the future, “physicians and health providers need to focus on providing equitable, guideline-directed treatment for their minority patients recently diagnosed with diabetes,” Dr. Marcondes emphasized. “Intervening early in the disease course will hopefully lead to a decrease in the rate of complications for racial/ethnic minorities. Clinicians, especially primary care physicians and providers, need to be aware that they are often the first encounter of many patients with the health care system. Effective communication and unbiased language on the part of clinicians will lead to stronger patient-physician relationships that foster opportunity to discuss disease prevention.

“Additional research is needed to evaluate the attitudes and biases of primary care providers and access the impact of patient navigation resources when treating minority patients with diabetes,” he concluded.

Digging Deeper into Disparities
“In diabetes, there are known racial and ethnic disparities such that minorities receive suboptimal screening and treatment, and have worse outcomes,” said Scott J. Pilla, MD, of The Johns Hopkins University School of Medicine, Baltimore, in an interview. 

“This study examines disparities in diabetes preventive measures in the U.S. using a national survey (NHIS) over the past decade. They took the important step of stratifying their analyses by health insurance and socioeconomic status which, in addition to race, may have a large impact,” said Dr. Pilla. However, “One critique of the poster is that it is unclear whether the researchers weighted their analyses to account for the nationally representative sampling of the NHIS survey,” he noted. 
Dr. Pilla said the finding that Hispanic patients had fewer diabetes preventive measures lines up with previous research in this area. 

“I was surprised that the disparities did not extend to black patients, who have been found to also receive suboptimal care compared to white patients in other studies,” he noted. 

The message for clinical practice: “Minorities with diabetes are at a higher risk of adverse diabetes outcomes and may need extra support and resources to achieve their evidence-based diabetes prevention,” Dr. Pilla said. 

“More research is needed to understand the root cause of racial and ethnic disparities in diabetes management to tease apart possible contributors including health insurance coverage, socioeconomic factors, cultural and community factors, and systemic racism. This will help inform targeted approaches to reducing disparities in diabetes care,” he emphasized.

The researchers had no relevant financial conflicts to disclose. Dr. Pilla had no financial conflicts to disclose. 

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with chronic migraine who turn to cannabis to relieve headache pain may be setting themselves up for medication overuse headache, preliminary research suggests, although the direction of the relationship is unclear. Researchers at Stanford (Calif.) University found a significant increase in the likelihood of medication overuse headache (rebound headache) in chronic migraine patients who use cannabis.

“This study shows that there is some kind of association between cannabis use and medication overuse headache in people with chronic migraine,” said lead investigator Niushen Zhang, MD, a clinical assistant professor at Stanford.

“But it is unclear at this time whether patients are using cannabis to treat medication overuse headache or if cannabis is contributing to the development medication overuse headache, or both,” she said.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

Sixfold increase

“Medication overuse occurs in about 1% to 3% of the general population. It affects nearly one-third of the patients (mostly patients with chronic migraine) seen at tertiary care centers such as the Stanford Headache Center,” Dr. Zhang said.

From clinical observations, patients with chronic migraine and medication overuse headache appear to be concomitantly using cannabis products, yet there is currently very little research on this topic, she added.

To investigate, the researchers reviewed the records of 368 adults who experienced chronic migraine (15 or more migraine days per month) for at least 1 year. Of the 368 patients, 150 were using cannabis, and 218 were not. In addition, 212 had medication overuse headache, and 156 did not.

Results showed that patients who used cannabis were nearly six times more likely to have medication overuse headache than those who did not use cannabis (odds ratio, 5.99; 95% confidence interval, 3.45-10.43; P < .0001).

There were significant bidirectional relationships between current cannabis use, opioid use, and medication overuse headache.
 

Jury out on cannabis for migraine

Commenting on the findings, Teshamae Monteith, MD, of the University of Miami, noted, “With increased legalization, greater access, and less stigmatization, there are more individuals using cannabis for migraine, but there is no solid evidence to suggest that cannabis is effective for acute or preventive treatment of migraine.”

The study is “interesting,” Dr. Monteith said, but, owing to methodologic limitations, it is not clear that cannabis contributes to medication overuse headache. “Patients with medication overuse headaches may have more comorbidities, such as anxiety, depression, and sleep disorders, that are driving the cannabis use. The patients on cannabis also had higher rates of opiate use, which itself is a stronger contributor to medication overuse headache and may indicate the presence of other pain disorders,” Dr. Monteith said.

“It is not clear if these patients were appropriately treated with migraine prevention; patients that use cannabis sometimes report that they prefer to avoid pharmaceutical treatments, such as antidepressants, etc., used for migraine,” Dr. Monteith noted.

She said that at this point, she would advise clinicians to ask about cannabis use “and let patients know that we do not know enough about the long-term effects of cannabis on the migraine brain.”

Most importantly, Dr. Monteith said, she would “encourage clinicians to be sensitive to the high prevalence of migraine, chronic migraine, and medication overuse. If we can treat more effectively and prevent migraine progression, which includes addressing comorbidities, there would be a lot less medication overuse headache.”

Also weighing in on the study, Jessica Ailani, MD, director, Medstar Georgetown Headache Center, Washington, D.C., noted that there is no conclusive evidence that cannabis is an effective acute or preventive treatment for migraine. “There is a suggestion that cannabis can help treat a migraine attack, but there is uncertainty about concentration of cannabidiol (CBD) to tetrahydrocannabinol (THC) needed to achieve pain freedom,” Dr. Ailani said.

“There has also been some concern about interactions between CBD and other medications used to treat migraine and that CBD can cause a condition known as reversible cerebral vasoconstrictive syndrome. These are reasons to be cautious with CBD,” Dr. Ailani added.

“At this time there is limited advice we can give our patients except that more studies need to be done. If cannabis is used, it should be reported, and medications that may interact with cannabis should be avoided. A headache calendar should be kept to ensure frequency of migraine and headache attacks do not go up,” said Dr. Ailani.

The study had no specific funding. Dr. Zhang, Dr. Monteith, and Dr. Ailani have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SEP-363856, an investigational nondopamine antipsychotic that’s been the focus of a trial in schizophrenia, has shown signals that it may improve psychosis symptoms in patients with Parkinson’s disease without worsening motor symptoms, according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.

In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.

“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.

The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).

Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D₂.

“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.

But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.

The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).

“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.

During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.

“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.

“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.

“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”

Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.

*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.

SEP-363856, an investigational nondopamine antipsychotic that’s been the focus of a trial in schizophrenia, has shown signals that it may improve psychosis symptoms in patients with Parkinson’s disease without worsening motor symptoms, according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.

In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.

“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.

The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).

Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D₂.

“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.

But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.

The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).

“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.

During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.

“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.

“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.

“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”

Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.

*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.

SEP-363856, an investigational nondopamine antipsychotic that’s been the focus of a trial in schizophrenia, has shown signals that it may improve psychosis symptoms in patients with Parkinson’s disease without worsening motor symptoms, according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.

In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.

“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.

The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).

Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D₂.

“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.

But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.

The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).

“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.

During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.

“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.

“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.

“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”

Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.

*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.

A gene therapy strategy has produced impressive results in patients with Sanfilippo syndrome type A (mucopolysaccharidosis IIIA). Most of the benefit from the treatment came in patients who began treatment at younger age, but comparisons to natural history controls showed profound improvement among many recipients, some of whom attained normal developmental trajectories.

The study was presented at the American Academy of Neurology’s 2021 annual meeting by Kevin Flanigan, MD, an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. He highlighted the improved developmental outcomes. “There’s been nothing shown to change the cognitive pathway of the disease. This is the first time it’s been seen as a treatment effect,” Dr. Flanigan said during a follow-up Q&A session.

The therapy was delivered using an adeno-associated virus-9 (AAV-9) vector, which led one questioner to ask about potential safety concerns, since AAV-associated risks date back to the death of Jesse Gelsinger in 1999. “There is concern about AAV therapies related to immune responses to potentially complement-mediated activation and thrombocytopenic syndrome, which has led to clinical holds on some other AAV-9 products related to muscular dystrophies. We’ve not seen signals of anything reminiscent of that, and we’re at AAV-9 dosages that are quite similar to what’s been used elsewhere in the field,” said Dr. Flanigan.

The results have him optimistic about the therapy. “I do think if it continues to be increasing divergent from the natural history, it will be questionable as to whether a subsequent trial will be necessary for this. That’s a decision for the [Food and Drug Administration] and the company to decide. Each observation point that goes by, each patient treated, and each time we get more data, I get more and more confident. It’s really gratifying to watch,” said Dr. Flanigan.

The study confirms the potential of gene replacement therapy autosomal recessive conditions, according to Nicholas Johnson, MD, associate professor of neurology at Virginia Commonwealth University, Richmond, as well as a fellow of the American Academy of Neurology. “Where the genetic problem is loss of gene function, the ability to replace that gene using a viral approach is going to be transformative across the board for many of these different conditions, including Sanfilippo syndrome,” said Dr. Johnson, who attended the session but was not involved in the research.

Toxicity could remain an issue, even in the absence of AAV-based safety concerns. “The rate limiting step in terms of gene replacement therapy development likely relates to the ability to provide those therapies to larger adults, because many approaches are weight based and it’s unclear what the upper limit of toxicity would be for adults,” said Dr. Johnson.
 

Transpher A study results

Dr. Flanigan presented results from Transpher A, a phase 1/2 clinical trial that has enrolled 20 patients to date in three cohorts: Cohort 1, with 3 patients, received 5 x 1,012 vg/kg, and had a mean follow-up of 58 months; cohort 2, with 3 patients, received 1 x 1,013 vg/kg, and had a mean follow-up of 49 months; and cohort 3, with 14 patients, received 3 x 1,013 vg/kg, with a mean follow-up of 24 months. Included patients ranged from birth to age 2, or older than age 2 with a development quotient of 60 or higher on the Bayley Scale.

Dr. Flanigan showed a plot of developmental progress compared with natural history controls, which showed that patients treated before age 2 or with a developmental quotient of 60 or higher had improved outcomes compared to other patients in the high dose cohort. They continued to show normal developmental progression at 30-36 months post treatment, at a time when the natural history data suggested they would suffer cognitive decline. Two years after administration, this group had cerebral spinal fluid levels of heparan sulfate that fell below the lower limit of detection. Patients in the high-dose cohort had normalized CSF levels of GM2 and GM3 gangliosides, and there were reductions in plasma heparan sulfate and urinary glycosaminoglycans. There was also a sustained decrease in liver volume.

The highest dose group was originally given to older patients, and most were similar to the natural history cohort, though some did stabilize. “More compellingly, patients (in the high-dose group) who were treated younger actually showed continued increase in development. One individual follows the normal development quotient line, and we would say that these are really quite distinct from what we typically see in patients,” said Dr. Flanigan.

The treatment was well tolerated. There were no deaths or treatment-related serious adverse events, and no clinically-significant adverse events within the first 5 years of follow-up.

The study was funded by Abeona Therapeutics. Dr. Flanigan has been on advisory boards for Apic Bio and 4D Molecular Therapeutics, consulted for Encoded Therapeutics, and has received royalties from Audentes Therapeutics. Dr. Flanigan has received funding from and been a consultant for Avidity.

A gene therapy strategy has produced impressive results in patients with Sanfilippo syndrome type A (mucopolysaccharidosis IIIA). Most of the benefit from the treatment came in patients who began treatment at younger age, but comparisons to natural history controls showed profound improvement among many recipients, some of whom attained normal developmental trajectories.

The study was presented at the American Academy of Neurology’s 2021 annual meeting by Kevin Flanigan, MD, an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. He highlighted the improved developmental outcomes. “There’s been nothing shown to change the cognitive pathway of the disease. This is the first time it’s been seen as a treatment effect,” Dr. Flanigan said during a follow-up Q&A session.

The therapy was delivered using an adeno-associated virus-9 (AAV-9) vector, which led one questioner to ask about potential safety concerns, since AAV-associated risks date back to the death of Jesse Gelsinger in 1999. “There is concern about AAV therapies related to immune responses to potentially complement-mediated activation and thrombocytopenic syndrome, which has led to clinical holds on some other AAV-9 products related to muscular dystrophies. We’ve not seen signals of anything reminiscent of that, and we’re at AAV-9 dosages that are quite similar to what’s been used elsewhere in the field,” said Dr. Flanigan.

The results have him optimistic about the therapy. “I do think if it continues to be increasing divergent from the natural history, it will be questionable as to whether a subsequent trial will be necessary for this. That’s a decision for the [Food and Drug Administration] and the company to decide. Each observation point that goes by, each patient treated, and each time we get more data, I get more and more confident. It’s really gratifying to watch,” said Dr. Flanigan.

The study confirms the potential of gene replacement therapy autosomal recessive conditions, according to Nicholas Johnson, MD, associate professor of neurology at Virginia Commonwealth University, Richmond, as well as a fellow of the American Academy of Neurology. “Where the genetic problem is loss of gene function, the ability to replace that gene using a viral approach is going to be transformative across the board for many of these different conditions, including Sanfilippo syndrome,” said Dr. Johnson, who attended the session but was not involved in the research.

Toxicity could remain an issue, even in the absence of AAV-based safety concerns. “The rate limiting step in terms of gene replacement therapy development likely relates to the ability to provide those therapies to larger adults, because many approaches are weight based and it’s unclear what the upper limit of toxicity would be for adults,” said Dr. Johnson.
 

Transpher A study results

Dr. Flanigan presented results from Transpher A, a phase 1/2 clinical trial that has enrolled 20 patients to date in three cohorts: Cohort 1, with 3 patients, received 5 x 1,012 vg/kg, and had a mean follow-up of 58 months; cohort 2, with 3 patients, received 1 x 1,013 vg/kg, and had a mean follow-up of 49 months; and cohort 3, with 14 patients, received 3 x 1,013 vg/kg, with a mean follow-up of 24 months. Included patients ranged from birth to age 2, or older than age 2 with a development quotient of 60 or higher on the Bayley Scale.

Dr. Flanigan showed a plot of developmental progress compared with natural history controls, which showed that patients treated before age 2 or with a developmental quotient of 60 or higher had improved outcomes compared to other patients in the high dose cohort. They continued to show normal developmental progression at 30-36 months post treatment, at a time when the natural history data suggested they would suffer cognitive decline. Two years after administration, this group had cerebral spinal fluid levels of heparan sulfate that fell below the lower limit of detection. Patients in the high-dose cohort had normalized CSF levels of GM2 and GM3 gangliosides, and there were reductions in plasma heparan sulfate and urinary glycosaminoglycans. There was also a sustained decrease in liver volume.

The highest dose group was originally given to older patients, and most were similar to the natural history cohort, though some did stabilize. “More compellingly, patients (in the high-dose group) who were treated younger actually showed continued increase in development. One individual follows the normal development quotient line, and we would say that these are really quite distinct from what we typically see in patients,” said Dr. Flanigan.

The treatment was well tolerated. There were no deaths or treatment-related serious adverse events, and no clinically-significant adverse events within the first 5 years of follow-up.

The study was funded by Abeona Therapeutics. Dr. Flanigan has been on advisory boards for Apic Bio and 4D Molecular Therapeutics, consulted for Encoded Therapeutics, and has received royalties from Audentes Therapeutics. Dr. Flanigan has received funding from and been a consultant for Avidity.

A gene therapy strategy has produced impressive results in patients with Sanfilippo syndrome type A (mucopolysaccharidosis IIIA). Most of the benefit from the treatment came in patients who began treatment at younger age, but comparisons to natural history controls showed profound improvement among many recipients, some of whom attained normal developmental trajectories.

The study was presented at the American Academy of Neurology’s 2021 annual meeting by Kevin Flanigan, MD, an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. He highlighted the improved developmental outcomes. “There’s been nothing shown to change the cognitive pathway of the disease. This is the first time it’s been seen as a treatment effect,” Dr. Flanigan said during a follow-up Q&A session.

The therapy was delivered using an adeno-associated virus-9 (AAV-9) vector, which led one questioner to ask about potential safety concerns, since AAV-associated risks date back to the death of Jesse Gelsinger in 1999. “There is concern about AAV therapies related to immune responses to potentially complement-mediated activation and thrombocytopenic syndrome, which has led to clinical holds on some other AAV-9 products related to muscular dystrophies. We’ve not seen signals of anything reminiscent of that, and we’re at AAV-9 dosages that are quite similar to what’s been used elsewhere in the field,” said Dr. Flanigan.

The results have him optimistic about the therapy. “I do think if it continues to be increasing divergent from the natural history, it will be questionable as to whether a subsequent trial will be necessary for this. That’s a decision for the [Food and Drug Administration] and the company to decide. Each observation point that goes by, each patient treated, and each time we get more data, I get more and more confident. It’s really gratifying to watch,” said Dr. Flanigan.

The study confirms the potential of gene replacement therapy autosomal recessive conditions, according to Nicholas Johnson, MD, associate professor of neurology at Virginia Commonwealth University, Richmond, as well as a fellow of the American Academy of Neurology. “Where the genetic problem is loss of gene function, the ability to replace that gene using a viral approach is going to be transformative across the board for many of these different conditions, including Sanfilippo syndrome,” said Dr. Johnson, who attended the session but was not involved in the research.

Toxicity could remain an issue, even in the absence of AAV-based safety concerns. “The rate limiting step in terms of gene replacement therapy development likely relates to the ability to provide those therapies to larger adults, because many approaches are weight based and it’s unclear what the upper limit of toxicity would be for adults,” said Dr. Johnson.
 

Transpher A study results

Dr. Flanigan presented results from Transpher A, a phase 1/2 clinical trial that has enrolled 20 patients to date in three cohorts: Cohort 1, with 3 patients, received 5 x 1,012 vg/kg, and had a mean follow-up of 58 months; cohort 2, with 3 patients, received 1 x 1,013 vg/kg, and had a mean follow-up of 49 months; and cohort 3, with 14 patients, received 3 x 1,013 vg/kg, with a mean follow-up of 24 months. Included patients ranged from birth to age 2, or older than age 2 with a development quotient of 60 or higher on the Bayley Scale.

Dr. Flanigan showed a plot of developmental progress compared with natural history controls, which showed that patients treated before age 2 or with a developmental quotient of 60 or higher had improved outcomes compared to other patients in the high dose cohort. They continued to show normal developmental progression at 30-36 months post treatment, at a time when the natural history data suggested they would suffer cognitive decline. Two years after administration, this group had cerebral spinal fluid levels of heparan sulfate that fell below the lower limit of detection. Patients in the high-dose cohort had normalized CSF levels of GM2 and GM3 gangliosides, and there were reductions in plasma heparan sulfate and urinary glycosaminoglycans. There was also a sustained decrease in liver volume.

The highest dose group was originally given to older patients, and most were similar to the natural history cohort, though some did stabilize. “More compellingly, patients (in the high-dose group) who were treated younger actually showed continued increase in development. One individual follows the normal development quotient line, and we would say that these are really quite distinct from what we typically see in patients,” said Dr. Flanigan.

The treatment was well tolerated. There were no deaths or treatment-related serious adverse events, and no clinically-significant adverse events within the first 5 years of follow-up.

The study was funded by Abeona Therapeutics. Dr. Flanigan has been on advisory boards for Apic Bio and 4D Molecular Therapeutics, consulted for Encoded Therapeutics, and has received royalties from Audentes Therapeutics. Dr. Flanigan has received funding from and been a consultant for Avidity.