Rheumatology News

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.