MDedge Rheumatology

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Risk for interstitial lung disease (ILD) was higher among patients with rheumatoid arthritis (RA) who were older, had longer disease duration, were male, were positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Major finding: The factors associated with an increased risk for RA-ILD were older age (weighted mean difference [WMD] 5.77 years; P < .00001), longer RA duration (WMD 0.80 years; P = .02), male sex (pooled odds ratio [OR] 1.92; P < .00001), positive RF (OR 1.72; P < .00001), positive ACPA (OR 1.58; P < .00001), higher ESR level (WMD 7.41 mm/h; P = .005), and higher CRP level (WMD 4.98 mg/L; P = .02).

Study details: Findings are from a systematic review and meta-analysis of 15 retrospective cohort studies and seven observational studies including 1887 patients with RA-ILD and 8066 patients with RA without ILD.

Disclosures: The authors received no specific funding for this study and declared no conflicts of interest.

Source: Zhang M et al. Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS One. 2023;18(6):e0286191 (Jun 23). Doi: 10.1371/journal.pone.0286191

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Interleukin-6 receptor inhibitors (IL-6Ri) effectively increased hemoglobin levels in patients with rheumatoid arthritis (RA) irrespective of their baseline levels, whereas Janus-kinase inhibitors (JAKi) improved hemoglobin levels in patients with RA and anemia and retained or decreased in those without anemia.

Major finding: From baseline to the 12-month follow-up, IL-6Ri increased hemoglobin levels in all patients with RA, irrespective of whether their baseline hemoglobin levels were low, intermediate, or high, and JAKi increased hemoglobin levels in those with RA and anemia, with levels remaining unaltered in those with intermediate hemoglobin levels and decreasing in those without anemia (all P < .001).

Study details: This study evaluated 2093 patients with RA from the ANSWER cohort who received biologic or targeted-synthetic disease-modifying antirheumatic drugs.

Disclosures: The ANSWER cohort study was supported by grants from 10 pharmaceutical companies, including AbbVie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., and others, and an information technology services company. Several authors declared receiving speaker fees, consulting fees, honoraria, or research grants from various sources.

Source: Nakayama Y et al. IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study. Rheumatology (Oxford). 2023 (Jun 24). Doi: 10.1093/rheumatology/kead299

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Higher adherence to the Mediterranean diet may help reduce disease impact, disease activity, and functional disability in patients with rheumatoid arthritis (RA).

Major finding: Patients with high vs low adherence to the Mediterranean diet had significantly lower Disease Activity Score of 28 Joints calculated with C-reactive protein (median 2.29 vs 3.27; P = .038), Health Assessment Questionnaire score (median 0.56 vs 1.00; P = .027), and Rheumatoid Arthritis Impact of Disease questionnaire score (median 3.51 vs 5.65; P = .032).

Study details: Findings are from a cross-sectional observational study including 120 patients with RA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Charneca S et al. The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability. Eur J Nutr. 2023 (Jun 24). Doi: 10.1007/s00394-023-03196-8

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Concomitant interstitial lung disease (ILD) is a significant factor associated with failure to achieve clinical remission and an increased risk for unfavorable clinical events in patients with rheumatoid arthritis (RA).

Major finding: The presence of ILD was significantly associated with failure to achieve Disease Activity Score in 28 Joints remission (adjusted hazard ratio [aHR] 0.71; P = .002) and increased risk for death (aHR 3.24; P < .001), hospitalized infections (aHR 2.60; P < .001), major adverse cardiac events (aHR 3.40; P < .001), and lung cancer (aHR 16.0; P < .001).

Study details: This study analyzed the data of 1522 patients with RA (ILD group n = 287; non-ILD group n = 1235) from the observational IORRA cohort.

Disclosures: This study was supported by the Ministry of Health, Labour, and Welfare of Japan and other sources. Some authors declared serving as consultants for or receiving research grants, research funding, or lecture, speaker, or consulting fees from various sources.

Source: Sugano E et al. Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: Results from the IORRA cohort. Rheumatology (Oxford). 2023 (Jun 28). Doi: 10.1093/rheumatology/kead317

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: Exposure to volatile organic compounds (VOC) significantly increased the risk for rheumatoid arthritis (RA), highlighting environmental pollutants as a risk factor for RA.

Major finding: Patients with RA had a significantly higher urine concentration of seven VOC than those without arthritis (all P < .05). The risk for RA was significantly higher among those in the highest vs lowest concentration quantile of AMCC (adjusted odds ratio [aOR] 2.173; 95% CI 1.021-4.627) and 3HPMA (aOR 2.663; 95% CI 1.288-5.508), with the parent compounds being N,N-Dimethylformamide and acrolein, respectively.

Study details: This cross-sectional study included 9536 participants with complete information on 15 urine VOC, of whom 618 participants had RA and 8918 did not have arthritis.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities of Central South University, the National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

Source: Lei T et al. The exposure to volatile organic chemicals associates positively with rheumatoid arthritis: A cross-sectional study from the NHANES program. Front Immunol. 2023;14:1098683 (Jun 19). Doi: 10.3389/fimmu.2023.1098683

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: In patients with established rheumatoid arthritis (RA) age ≥ 65 years, an add-on low-dose prednisolone administration for 2 years led to a marginal weight gain, which appeared mostly as a beneficial increase in lean mass.

Major finding: At 2 years, the body weight increased slightly with 5 mg/day prednisolone (mean change +0.9 kg; 95% CI 0.3-1.6 kg), whereas there was a non-significant decrease with placebo (between-treatment difference 1.3 kg; P < .01). The change in body weight with prednisolone was mostly due to increased lean mass rather than fat mass and was not significantly related to disease activity.

Study details: This substudy of the phase 4 GLORIA trial included 449 patients aged ≥65 years with active RA who were randomly assigned to receive placebo (n = 225) or 5 mg/day prednisolone (n = 224) along with standard care for 2 years.

Disclosures: The GLORIA study was funded by the European Union’s Horizon 2020 research and innovation program. M Boers and MR Kok declared ties with various sources. The other authors declared no competing interests.

Source: Güler-Yüksel M et al. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open. 2023;9:e002905 (Jun 22). Doi: 10.1136/rmdopen-2022-002905

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278

Key clinical point: A substantial proportion of patients with early rheumatoid arthritis (RA) had unacceptably high levels of pain with or without low inflammation at 2 years after diagnosis, with joint tenderness at the 3-month follow-up predicting long-term pain despite low inflammation.

Major finding: Nearly one third of patients with early RA had unacceptable pain levels after 2 years of follow-up, with almost 80% of them also having low inflammation. At the 3-month follow-up, the difference between tender and swollen joint counts predicted the 2-year risk for unacceptable pain (odds ratio [OR] 2.00; P < .05) and unacceptable pain with low inflammation (OR 2.02; P < .05).

Study details: Findings are from a retrospective study including 275 patients with early RA.

Disclosures: This study was supported by The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared working as a medical solution lead in rheumatology or receiving consulting fees, speaking fees, and unrestricted grant from various sources. Three authors declared no conflicts of interest.

Source: Eberhard A et al. Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead278

Key clinical point: Functional disabilities involving the hands started earlier and were more frequent and severe than those involving feet in patients with clinically suspect arthralgia (CSA) who progressed toward rheumatoid arthritis (RA) or clinical inflammatory arthritis (IA).

Major finding: In patients with RA development, hand disabilities occurred earlier and were more frequent and severe (mean difference over time 0.41 units; P < .001) than foot disabilities. The evaluation of tender joints and subclinical joint inflammation showed similar findings for hand and foot involvement.

Study details: This study longitudinally assessed 600 patients with CSA who developed clinical IA or had at least 1 year of follow-up.

Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. AHM van der Helm-van Mil declared being an Editorial Board Member for RMD Open. The other authors did not report any conflicts of interest.

Source: Khidir SJH et al. Joint involvement in RA starts predominantly in the hands: Functional, clinical and imaging studies in clinically suspect arthralgia and during progression to RA. RMD Open. 2023;9:e003107 (Jun 16). Doi: 10.1136/rmdopen-2023-003107

Key clinical point: Functional disabilities involving the hands started earlier and were more frequent and severe than those involving feet in patients with clinically suspect arthralgia (CSA) who progressed toward rheumatoid arthritis (RA) or clinical inflammatory arthritis (IA).

Major finding: In patients with RA development, hand disabilities occurred earlier and were more frequent and severe (mean difference over time 0.41 units; P < .001) than foot disabilities. The evaluation of tender joints and subclinical joint inflammation showed similar findings for hand and foot involvement.

Study details: This study longitudinally assessed 600 patients with CSA who developed clinical IA or had at least 1 year of follow-up.

Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. AHM van der Helm-van Mil declared being an Editorial Board Member for RMD Open. The other authors did not report any conflicts of interest.

Source: Khidir SJH et al. Joint involvement in RA starts predominantly in the hands: Functional, clinical and imaging studies in clinically suspect arthralgia and during progression to RA. RMD Open. 2023;9:e003107 (Jun 16). Doi: 10.1136/rmdopen-2023-003107

Key clinical point: Functional disabilities involving the hands started earlier and were more frequent and severe than those involving feet in patients with clinically suspect arthralgia (CSA) who progressed toward rheumatoid arthritis (RA) or clinical inflammatory arthritis (IA).

Major finding: In patients with RA development, hand disabilities occurred earlier and were more frequent and severe (mean difference over time 0.41 units; P < .001) than foot disabilities. The evaluation of tender joints and subclinical joint inflammation showed similar findings for hand and foot involvement.

Study details: This study longitudinally assessed 600 patients with CSA who developed clinical IA or had at least 1 year of follow-up.

Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. AHM van der Helm-van Mil declared being an Editorial Board Member for RMD Open. The other authors did not report any conflicts of interest.

Source: Khidir SJH et al. Joint involvement in RA starts predominantly in the hands: Functional, clinical and imaging studies in clinically suspect arthralgia and during progression to RA. RMD Open. 2023;9:e003107 (Jun 16). Doi: 10.1136/rmdopen-2023-003107