Rheumatology News

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

Edward W. Cowen, MD, MHSc

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

Image courtesy of JAMA Network

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

Edward W. Cowen, MD, MHSc

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

Image courtesy of JAMA Network

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

Edward W. Cowen, MD, MHSc

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

Image courtesy of JAMA Network

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

A single course of treatment with emotional awareness and expression therapy (EAET) was associated with a significantly greater reduction in chronic pain severity than cognitive-behavioral therapy (CBT), the current psychotherapeutic gold standard, a new study suggested.

Two thirds of the patients who received EAET reported at least a 30% reduction in pain compared with 17% of those who received CBT. The randomized clinical trial also showed that individuals with depression and anxiety responded more favorably to EAET, a novel finding.

The study is one of only a few to directly compare EAET with CBT.

“Most people with chronic pain don’t consider psychotherapy at all,” said study investigator Brandon C. Yarns, MD, a staff psychiatrist at the VA Greater Los Angeles Healthcare System, and clinical professor of health sciences at the Department of Psychiatry and Biobehavioral Sciences, UCLA Health.

Although patients were allowed to continue medication for pain and other comorbidities during the study, those who received EAET “had larger improvements in pain, depression, and anxiety,” Dr. Yarns said. “That suggests that the effect was due to the EAET.”

The findings were published online in JAMA Network Open.
 

‘Gold Standard’

EAET was first used in the early 2010s. In the therapy, patients are asked to recall a difficult or traumatic memory, engage in experiencing how the related emotions feel in the body, express those feelings in words, and release or let them go. They are taught that the brain’s perception of pain is strongly influenced by the evasion of grief, fear, rage, or guilt, Dr. Yarns said.

This contrasts with CBT — considered the current gold standard for chronic pain — which teaches patients to improve the ability to tolerate pain though guided imagery, muscle relaxation, and other exercises and to adapt their thinking to change how they think about pain.

Although prior studies suggested EAET is effective in reducing pain in fibromyalgia and chronic musculoskeletal, pelvic, and head pain, most included primarily younger, female patients.

The research is the “first full-scale evaluation of EAET, to our knowledge, in a medically or psychiatrically complex, racially and ethnically diverse, older sample comprising predominantly men,” investigators wrote.

The trial enrolled 126 veterans (92% men; 55% Black or African American) aged 60-95 years with at least 3 months of musculoskeletal pain. More than two thirds of patients had a psychiatric diagnosis, with about one third having posttraumatic stress disorder (PTSD). Almost all had back pain, and many had pain in multiple locations.

All services were delivered in-person at the US Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles. Half underwent CBT, while the other half received EAET.

Each patient had one 90-minute individual session and eight additional 90-minute group sessions.

Patients were asked to rate their pain using a 0-10 scale in the Brief Pain Inventory (BPI) before starting treatment, at the end of the nine sessions (at week 10), and 6 months after the sessions ended. Baseline BPI score for both groups was a mean of around 6.

Post treatment, people in the EAET versus CBT group had a mean two-point reduction versus 0.60 reduction, respectively, on the BPI scale. A clinically significant reduction in pain — defined as ≥ 30% decrease — was reported in 63% of EAET patients versus 17% of CBT patients (odds ratio [OR], 21.54; P < .001).

At 6 months, the mean reduction was 1.2 for the EAET group compared with 0.25 for the CBT group, and 40% of the EAET group reported a clinically significant reduction in pain.

A little more than a third (35%) of veterans receiving EAET reported at least a 50% reduction in pain at 10 weeks compared with 7% of those receiving CBT. At 6 months, 16% of the EAET arm reported a halving of their pain.

EAET was also superior to CBT in reducing anxiety, depression, and PTSD symptoms at the 10-week mark.
 

More Work Needed

In an accompanying editorial, Matthias Karst, MD, PhD, a clinician with the Pain Clinic, Hannover Medical School, in Hannover, Germany, noted that EAET’s effects “are significantly superior to those of CBT in almost all dimensions, even after 6 months.”

EAET “assigns a special place to the integration of the body into the emotional experience,” he wrote.

The study demonstrated that “the evocation and expression of emotions is superior to the mere cognitive discussion of these emotions in therapy of patients with chronic pain.”

Commenting on the findings, Traci J. Speed, MD, PhD, assistant professor of psychiatry and behavioral sciences and an attending psychiatrist of the Johns Hopkins Pain Treatment Program at Johns Hopkins University, Baltimore, called the study “ground-breaking” because it showed effectiveness in people with high rates of PTSD, anxiety, and depression.

“It is a little bit surprising how impressive the study outcomes are in terms of maintaining the effects at the end of the treatment and sustaining some of the effects on pain sensitivity even at the 6-month follow-up,” said Dr. Speed, who was not part of the study.

However, she continued, “I don’t think it changes the current standard of practice yet. CBT has decades of research and evidence that it is effective for chronic pain and that will I think continue to be the standard of care.”

Although EAET is in its infancy, chronic pain experts are interested in learning more about the therapy, Dr. Speed added.

“It blends well with the current techniques and extends the current gold standard treatment approaches,” she said. “We are starting to really appreciate the role that emotions play in pain sensitivity.”

Both Dr. Karst and Dr. Speed noted that more study is needed to determine the sustainability of treatment effects.

Dr. Yarns agreed. “We need more research on what the appropriate dose is and perhaps how one might go about personalizing that for the patient,” he said.

The study was funded by a career development award to Dr. Yarns from the VA Clinical Science Research and Development Service. Dr. Yarns reported receiving grants from the US Department of Veterans Affairs during the study. Other authors’ disclosures are in the original article. Dr. Speed reported no conflicts.
 

A version of this article appeared on Medscape.com.

A single course of treatment with emotional awareness and expression therapy (EAET) was associated with a significantly greater reduction in chronic pain severity than cognitive-behavioral therapy (CBT), the current psychotherapeutic gold standard, a new study suggested.

Two thirds of the patients who received EAET reported at least a 30% reduction in pain compared with 17% of those who received CBT. The randomized clinical trial also showed that individuals with depression and anxiety responded more favorably to EAET, a novel finding.

The study is one of only a few to directly compare EAET with CBT.

“Most people with chronic pain don’t consider psychotherapy at all,” said study investigator Brandon C. Yarns, MD, a staff psychiatrist at the VA Greater Los Angeles Healthcare System, and clinical professor of health sciences at the Department of Psychiatry and Biobehavioral Sciences, UCLA Health.

Although patients were allowed to continue medication for pain and other comorbidities during the study, those who received EAET “had larger improvements in pain, depression, and anxiety,” Dr. Yarns said. “That suggests that the effect was due to the EAET.”

The findings were published online in JAMA Network Open.
 

‘Gold Standard’

EAET was first used in the early 2010s. In the therapy, patients are asked to recall a difficult or traumatic memory, engage in experiencing how the related emotions feel in the body, express those feelings in words, and release or let them go. They are taught that the brain’s perception of pain is strongly influenced by the evasion of grief, fear, rage, or guilt, Dr. Yarns said.

This contrasts with CBT — considered the current gold standard for chronic pain — which teaches patients to improve the ability to tolerate pain though guided imagery, muscle relaxation, and other exercises and to adapt their thinking to change how they think about pain.

Although prior studies suggested EAET is effective in reducing pain in fibromyalgia and chronic musculoskeletal, pelvic, and head pain, most included primarily younger, female patients.

The research is the “first full-scale evaluation of EAET, to our knowledge, in a medically or psychiatrically complex, racially and ethnically diverse, older sample comprising predominantly men,” investigators wrote.

The trial enrolled 126 veterans (92% men; 55% Black or African American) aged 60-95 years with at least 3 months of musculoskeletal pain. More than two thirds of patients had a psychiatric diagnosis, with about one third having posttraumatic stress disorder (PTSD). Almost all had back pain, and many had pain in multiple locations.

All services were delivered in-person at the US Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles. Half underwent CBT, while the other half received EAET.

Each patient had one 90-minute individual session and eight additional 90-minute group sessions.

Patients were asked to rate their pain using a 0-10 scale in the Brief Pain Inventory (BPI) before starting treatment, at the end of the nine sessions (at week 10), and 6 months after the sessions ended. Baseline BPI score for both groups was a mean of around 6.

Post treatment, people in the EAET versus CBT group had a mean two-point reduction versus 0.60 reduction, respectively, on the BPI scale. A clinically significant reduction in pain — defined as ≥ 30% decrease — was reported in 63% of EAET patients versus 17% of CBT patients (odds ratio [OR], 21.54; P < .001).

At 6 months, the mean reduction was 1.2 for the EAET group compared with 0.25 for the CBT group, and 40% of the EAET group reported a clinically significant reduction in pain.

A little more than a third (35%) of veterans receiving EAET reported at least a 50% reduction in pain at 10 weeks compared with 7% of those receiving CBT. At 6 months, 16% of the EAET arm reported a halving of their pain.

EAET was also superior to CBT in reducing anxiety, depression, and PTSD symptoms at the 10-week mark.
 

More Work Needed

In an accompanying editorial, Matthias Karst, MD, PhD, a clinician with the Pain Clinic, Hannover Medical School, in Hannover, Germany, noted that EAET’s effects “are significantly superior to those of CBT in almost all dimensions, even after 6 months.”

EAET “assigns a special place to the integration of the body into the emotional experience,” he wrote.

The study demonstrated that “the evocation and expression of emotions is superior to the mere cognitive discussion of these emotions in therapy of patients with chronic pain.”

Commenting on the findings, Traci J. Speed, MD, PhD, assistant professor of psychiatry and behavioral sciences and an attending psychiatrist of the Johns Hopkins Pain Treatment Program at Johns Hopkins University, Baltimore, called the study “ground-breaking” because it showed effectiveness in people with high rates of PTSD, anxiety, and depression.

“It is a little bit surprising how impressive the study outcomes are in terms of maintaining the effects at the end of the treatment and sustaining some of the effects on pain sensitivity even at the 6-month follow-up,” said Dr. Speed, who was not part of the study.

However, she continued, “I don’t think it changes the current standard of practice yet. CBT has decades of research and evidence that it is effective for chronic pain and that will I think continue to be the standard of care.”

Although EAET is in its infancy, chronic pain experts are interested in learning more about the therapy, Dr. Speed added.

“It blends well with the current techniques and extends the current gold standard treatment approaches,” she said. “We are starting to really appreciate the role that emotions play in pain sensitivity.”

Both Dr. Karst and Dr. Speed noted that more study is needed to determine the sustainability of treatment effects.

Dr. Yarns agreed. “We need more research on what the appropriate dose is and perhaps how one might go about personalizing that for the patient,” he said.

The study was funded by a career development award to Dr. Yarns from the VA Clinical Science Research and Development Service. Dr. Yarns reported receiving grants from the US Department of Veterans Affairs during the study. Other authors’ disclosures are in the original article. Dr. Speed reported no conflicts.
 

A version of this article appeared on Medscape.com.

A single course of treatment with emotional awareness and expression therapy (EAET) was associated with a significantly greater reduction in chronic pain severity than cognitive-behavioral therapy (CBT), the current psychotherapeutic gold standard, a new study suggested.

Two thirds of the patients who received EAET reported at least a 30% reduction in pain compared with 17% of those who received CBT. The randomized clinical trial also showed that individuals with depression and anxiety responded more favorably to EAET, a novel finding.

The study is one of only a few to directly compare EAET with CBT.

“Most people with chronic pain don’t consider psychotherapy at all,” said study investigator Brandon C. Yarns, MD, a staff psychiatrist at the VA Greater Los Angeles Healthcare System, and clinical professor of health sciences at the Department of Psychiatry and Biobehavioral Sciences, UCLA Health.

Although patients were allowed to continue medication for pain and other comorbidities during the study, those who received EAET “had larger improvements in pain, depression, and anxiety,” Dr. Yarns said. “That suggests that the effect was due to the EAET.”

The findings were published online in JAMA Network Open.
 

‘Gold Standard’

EAET was first used in the early 2010s. In the therapy, patients are asked to recall a difficult or traumatic memory, engage in experiencing how the related emotions feel in the body, express those feelings in words, and release or let them go. They are taught that the brain’s perception of pain is strongly influenced by the evasion of grief, fear, rage, or guilt, Dr. Yarns said.

This contrasts with CBT — considered the current gold standard for chronic pain — which teaches patients to improve the ability to tolerate pain though guided imagery, muscle relaxation, and other exercises and to adapt their thinking to change how they think about pain.

Although prior studies suggested EAET is effective in reducing pain in fibromyalgia and chronic musculoskeletal, pelvic, and head pain, most included primarily younger, female patients.

The research is the “first full-scale evaluation of EAET, to our knowledge, in a medically or psychiatrically complex, racially and ethnically diverse, older sample comprising predominantly men,” investigators wrote.

The trial enrolled 126 veterans (92% men; 55% Black or African American) aged 60-95 years with at least 3 months of musculoskeletal pain. More than two thirds of patients had a psychiatric diagnosis, with about one third having posttraumatic stress disorder (PTSD). Almost all had back pain, and many had pain in multiple locations.

All services were delivered in-person at the US Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles. Half underwent CBT, while the other half received EAET.

Each patient had one 90-minute individual session and eight additional 90-minute group sessions.

Patients were asked to rate their pain using a 0-10 scale in the Brief Pain Inventory (BPI) before starting treatment, at the end of the nine sessions (at week 10), and 6 months after the sessions ended. Baseline BPI score for both groups was a mean of around 6.

Post treatment, people in the EAET versus CBT group had a mean two-point reduction versus 0.60 reduction, respectively, on the BPI scale. A clinically significant reduction in pain — defined as ≥ 30% decrease — was reported in 63% of EAET patients versus 17% of CBT patients (odds ratio [OR], 21.54; P < .001).

At 6 months, the mean reduction was 1.2 for the EAET group compared with 0.25 for the CBT group, and 40% of the EAET group reported a clinically significant reduction in pain.

A little more than a third (35%) of veterans receiving EAET reported at least a 50% reduction in pain at 10 weeks compared with 7% of those receiving CBT. At 6 months, 16% of the EAET arm reported a halving of their pain.

EAET was also superior to CBT in reducing anxiety, depression, and PTSD symptoms at the 10-week mark.
 

More Work Needed

In an accompanying editorial, Matthias Karst, MD, PhD, a clinician with the Pain Clinic, Hannover Medical School, in Hannover, Germany, noted that EAET’s effects “are significantly superior to those of CBT in almost all dimensions, even after 6 months.”

EAET “assigns a special place to the integration of the body into the emotional experience,” he wrote.

The study demonstrated that “the evocation and expression of emotions is superior to the mere cognitive discussion of these emotions in therapy of patients with chronic pain.”

Commenting on the findings, Traci J. Speed, MD, PhD, assistant professor of psychiatry and behavioral sciences and an attending psychiatrist of the Johns Hopkins Pain Treatment Program at Johns Hopkins University, Baltimore, called the study “ground-breaking” because it showed effectiveness in people with high rates of PTSD, anxiety, and depression.

“It is a little bit surprising how impressive the study outcomes are in terms of maintaining the effects at the end of the treatment and sustaining some of the effects on pain sensitivity even at the 6-month follow-up,” said Dr. Speed, who was not part of the study.

However, she continued, “I don’t think it changes the current standard of practice yet. CBT has decades of research and evidence that it is effective for chronic pain and that will I think continue to be the standard of care.”

Although EAET is in its infancy, chronic pain experts are interested in learning more about the therapy, Dr. Speed added.

“It blends well with the current techniques and extends the current gold standard treatment approaches,” she said. “We are starting to really appreciate the role that emotions play in pain sensitivity.”

Both Dr. Karst and Dr. Speed noted that more study is needed to determine the sustainability of treatment effects.

Dr. Yarns agreed. “We need more research on what the appropriate dose is and perhaps how one might go about personalizing that for the patient,” he said.

The study was funded by a career development award to Dr. Yarns from the VA Clinical Science Research and Development Service. Dr. Yarns reported receiving grants from the US Department of Veterans Affairs during the study. Other authors’ disclosures are in the original article. Dr. Speed reported no conflicts.
 

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

Ted Bosworth/Medscape Medical News

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise. 

Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.

While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.

“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”

There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.

In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft