Osteoarthritis

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

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.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.

METHODOLOGY:

• Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
• Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
• Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
• Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.

TAKEAWAY:

• A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
• The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
• Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.

IN PRACTICE:

“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.

SOURCE:

The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.

DISCLOSURES:

The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.

METHODOLOGY:

• Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
• Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
• Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
• Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.

TAKEAWAY:

• A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
• The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
• Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.

IN PRACTICE:

“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.

SOURCE:

The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.

DISCLOSURES:

The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.

METHODOLOGY:

• Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
• Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
• Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
• Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.

TAKEAWAY:

• A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
• The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
• Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.

IN PRACTICE:

“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.

SOURCE:

The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.

LIMITATIONS:

The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.

DISCLOSURES:

The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Adding arthroscopic surgery to nonoperative management neither delays nor accelerates the timing of total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA).

METHODOLOGY:

• Some case series show that arthroscopic surgery for knee OA may delay more invasive procedures, such as TKA or osteotomy, while longitudinal cohort studies often contradict this. Current OA guidelines are yet to address this issue.
• This secondary analysis of a randomized trial compared the long-term incidence of TKA in 178 patients (mean age, 59 years; 64.3% women) with knee OA who were referred for potential arthroscopic surgery at a tertiary care center in Canada.
• The patients received nonoperative care with or without additional arthroscopic surgery.
• Patients in the arthroscopic surgery group had specific knee procedures (resection of degenerative knee tissues) along with nonoperative management (physical therapy plus medications as required), while the control group received nonoperative management alone.
• The primary outcome was TKA on the knee being studied, and the secondary outcome was TKA or osteotomy on either knee.

TAKEAWAY:

• During a median follow-up of 13.8 years, 37.6% of patients underwent TKA, with comparable proportions of patients in the arthroscopic surgery and control groups undergoing TKA (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.52-1.40).
• The rates of TKA or osteotomy on either knee were similar in both groups (aHR, 0.91; 95% CI, 0.59-1.41).
• A time-stratified analysis done for 0-5 years, 5-10 years, and beyond 10 years of follow-up also showed a consistent interpretation.
• When patients with crossover to arthroscopic surgery during the follow-up were included, the results remained similar for both the primary (HR, 0.88; 95% CI, 0.53-1.44) and secondary (HR, 1.08; 95% CI, 0.69-1.68) outcomes.

IN PRACTICE:

“Our study findings do not support the use of arthroscopic surgery for OA of the knee.” “Arthroscopic surgery does not provide additional benefit to nonoperative management for improving pain, stiffness, and function and is likely not cost-effective at 2 years of follow-up,” the authors wrote.

SOURCE:

This study was led by Trevor B. Birmingham, PhD, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario, London, Ontario, Canada. It was published online in JAMA Network Open

LIMITATIONS:

The study was designed to assess differences in 2-year patient-reported outcomes rather than long-term TKA incidence. Factors influencing decisions to undergo TKA or osteotomy were not considered. Moreover, the effects observed in this study should be evaluated considering the estimated confidence intervals.

DISCLOSURES:

This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors declared consulting, performing contracted services, or receiving grant funding, royalties, and nonfinancial support from various sources.

A version of this article appeared on Medscape.com.