Rheumatoid Arthritis

Key clinical point: Higher perceived distress was associated with elevated risk of developing inflammatory arthritis (IA) in an at-risk population having either positive rheumatoid arthritis (RA)-related autoantibodies or inherent genetic risk based on family history.

Major finding: A 1-point increase in the perceived distress score was significantly associated with a 10% increase in the risk of incident IA (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 1.02-1.19). Total perceived stress (aHR, 1.05; 95% CI, 0.99-1.10) and self-efficacy (aHR, 1.04; 95% CI, 0.91-1.18) scores were not significantly associated with the risk of incident IA.

Study details: This prospective cohort study evaluated 448 participants at an increased risk of developing future RA (either first-degree relatives of RA probands or positive for anti-citrullinated protein antibodies) from the Studies of the Etiologies of Rheumatoid Arthritis cohort.

Disclosures: The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Polinski KJ et al. Arthritis Care Res (Hoboken). 2020 Nov 6. doi: 10.1002/acr.24085.

Key clinical point: Higher perceived distress was associated with elevated risk of developing inflammatory arthritis (IA) in an at-risk population having either positive rheumatoid arthritis (RA)-related autoantibodies or inherent genetic risk based on family history.

Major finding: A 1-point increase in the perceived distress score was significantly associated with a 10% increase in the risk of incident IA (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 1.02-1.19). Total perceived stress (aHR, 1.05; 95% CI, 0.99-1.10) and self-efficacy (aHR, 1.04; 95% CI, 0.91-1.18) scores were not significantly associated with the risk of incident IA.

Study details: This prospective cohort study evaluated 448 participants at an increased risk of developing future RA (either first-degree relatives of RA probands or positive for anti-citrullinated protein antibodies) from the Studies of the Etiologies of Rheumatoid Arthritis cohort.

Disclosures: The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Polinski KJ et al. Arthritis Care Res (Hoboken). 2020 Nov 6. doi: 10.1002/acr.24085.

Key clinical point: Higher perceived distress was associated with elevated risk of developing inflammatory arthritis (IA) in an at-risk population having either positive rheumatoid arthritis (RA)-related autoantibodies or inherent genetic risk based on family history.

Major finding: A 1-point increase in the perceived distress score was significantly associated with a 10% increase in the risk of incident IA (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 1.02-1.19). Total perceived stress (aHR, 1.05; 95% CI, 0.99-1.10) and self-efficacy (aHR, 1.04; 95% CI, 0.91-1.18) scores were not significantly associated with the risk of incident IA.

Study details: This prospective cohort study evaluated 448 participants at an increased risk of developing future RA (either first-degree relatives of RA probands or positive for anti-citrullinated protein antibodies) from the Studies of the Etiologies of Rheumatoid Arthritis cohort.

Disclosures: The study was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Polinski KJ et al. Arthritis Care Res (Hoboken). 2020 Nov 6. doi: 10.1002/acr.24085.

Key clinical point: The appearance of total antinuclear antibodies (ANA) before administration of TNF-α inhibitors (TNFi) is a risk factor for the appearance of antidrug antibodies (ADrA) and treatment failure.

Major finding: ADrA appeared in 36.8% and 30.2% of patients treated with infliximab (IFX) and adalimumab (ADA), respectively; all being positive for total ANA before TNFi administration. High titers of total ANA before IFX treatment were significantly associated with inefficacy and discontinuation of treatment.

Study details: The data come from observational study of 121 patients with RA newly introduced to 3 classes of TNFi.

Disclosures: The study did not receive any funding. S Kumagai reported ties with various pharmaceutical companies. The other authors reported no conflicts of interest.

Source: Mori A et al. PLoS One. 2020 Dec 14. doi: 10.1371/journal.pone.0243729.

Key clinical point: The appearance of total antinuclear antibodies (ANA) before administration of TNF-α inhibitors (TNFi) is a risk factor for the appearance of antidrug antibodies (ADrA) and treatment failure.

Major finding: ADrA appeared in 36.8% and 30.2% of patients treated with infliximab (IFX) and adalimumab (ADA), respectively; all being positive for total ANA before TNFi administration. High titers of total ANA before IFX treatment were significantly associated with inefficacy and discontinuation of treatment.

Study details: The data come from observational study of 121 patients with RA newly introduced to 3 classes of TNFi.

Disclosures: The study did not receive any funding. S Kumagai reported ties with various pharmaceutical companies. The other authors reported no conflicts of interest.

Source: Mori A et al. PLoS One. 2020 Dec 14. doi: 10.1371/journal.pone.0243729.

Key clinical point: The appearance of total antinuclear antibodies (ANA) before administration of TNF-α inhibitors (TNFi) is a risk factor for the appearance of antidrug antibodies (ADrA) and treatment failure.

Major finding: ADrA appeared in 36.8% and 30.2% of patients treated with infliximab (IFX) and adalimumab (ADA), respectively; all being positive for total ANA before TNFi administration. High titers of total ANA before IFX treatment were significantly associated with inefficacy and discontinuation of treatment.

Study details: The data come from observational study of 121 patients with RA newly introduced to 3 classes of TNFi.

Disclosures: The study did not receive any funding. S Kumagai reported ties with various pharmaceutical companies. The other authors reported no conflicts of interest.

Source: Mori A et al. PLoS One. 2020 Dec 14. doi: 10.1371/journal.pone.0243729.

Key clinical point: Baricitinib 4 mg may be considered for long-term treatment of patients with moderate to severe rheumatoid arthritis (RA) who were either naïve to disease-modifying antirheumatic drugs (DMARDs) or had inadequate response (IR) to methotrexate (MTX).

Major finding: At week 148, low disease activity was achieved in up to 61% of DMARD-naïve patients and 59% of MTX-IR patients initially treated with baricitinib. Baricitinib was well-tolerated.

Study details: Analysis of data from 2 completed (RA-BEGIN [n = 584] and RA-BEAM [n = 1,305]) and 1 ongoing long-term extension (RA-BEYOND) phase 3 trials involving either DMARD-naïve or MTX-IR patients.

Disclosures: The study was supported by Eli Lilly and Company. L Xie, B Jia, A Elias, A Cardoso, R Ortmann and C Walls are full-time employees of Eli Lilly and Company and may own stock or stock options in the company.

Source: Smolen JS et al. Rheumatology (Oxford). 2020 Nov 17. doi: 10.1093/rheumatology/keaa576.

Key clinical point: Baricitinib 4 mg may be considered for long-term treatment of patients with moderate to severe rheumatoid arthritis (RA) who were either naïve to disease-modifying antirheumatic drugs (DMARDs) or had inadequate response (IR) to methotrexate (MTX).

Major finding: At week 148, low disease activity was achieved in up to 61% of DMARD-naïve patients and 59% of MTX-IR patients initially treated with baricitinib. Baricitinib was well-tolerated.

Study details: Analysis of data from 2 completed (RA-BEGIN [n = 584] and RA-BEAM [n = 1,305]) and 1 ongoing long-term extension (RA-BEYOND) phase 3 trials involving either DMARD-naïve or MTX-IR patients.

Disclosures: The study was supported by Eli Lilly and Company. L Xie, B Jia, A Elias, A Cardoso, R Ortmann and C Walls are full-time employees of Eli Lilly and Company and may own stock or stock options in the company.

Source: Smolen JS et al. Rheumatology (Oxford). 2020 Nov 17. doi: 10.1093/rheumatology/keaa576.

Key clinical point: Baricitinib 4 mg may be considered for long-term treatment of patients with moderate to severe rheumatoid arthritis (RA) who were either naïve to disease-modifying antirheumatic drugs (DMARDs) or had inadequate response (IR) to methotrexate (MTX).

Major finding: At week 148, low disease activity was achieved in up to 61% of DMARD-naïve patients and 59% of MTX-IR patients initially treated with baricitinib. Baricitinib was well-tolerated.

Study details: Analysis of data from 2 completed (RA-BEGIN [n = 584] and RA-BEAM [n = 1,305]) and 1 ongoing long-term extension (RA-BEYOND) phase 3 trials involving either DMARD-naïve or MTX-IR patients.

Disclosures: The study was supported by Eli Lilly and Company. L Xie, B Jia, A Elias, A Cardoso, R Ortmann and C Walls are full-time employees of Eli Lilly and Company and may own stock or stock options in the company.

Source: Smolen JS et al. Rheumatology (Oxford). 2020 Nov 17. doi: 10.1093/rheumatology/keaa576.

Key clinical point: In anti-citrullinated protein antibodies (ACPA)-negative rheumatoid arthritis (RA), a significant decline in the disease activity score (DAS) within the first 4 months after diagnosis was associated with a higher probability of achieving sustained disease-modifying anti-rheumatic drugs (DMARDs)-free remission (SDFR).

Major finding: In patients with ACPA-negative RA, the decline in DAS within the first 4 months was stronger in the SDFR vs. non-SDFR group (−1.73 vs. −1.07 units; P less than .001). SDFR incidence was high (70.2%) and rare (7.1%) when absolute DAS level at 4 months was less than 1.6 and 3.6 or greater, respectively.

Study details: The study cohort included 772 consecutive patients with RA promptly treated with conventional DMARDs. Patients were classified into SDFR (n=149) and non-SDFR (n=623) groups.

Disclosures: The study was supported by the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Verstappen M et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02368-9.

Key clinical point: In anti-citrullinated protein antibodies (ACPA)-negative rheumatoid arthritis (RA), a significant decline in the disease activity score (DAS) within the first 4 months after diagnosis was associated with a higher probability of achieving sustained disease-modifying anti-rheumatic drugs (DMARDs)-free remission (SDFR).

Major finding: In patients with ACPA-negative RA, the decline in DAS within the first 4 months was stronger in the SDFR vs. non-SDFR group (−1.73 vs. −1.07 units; P less than .001). SDFR incidence was high (70.2%) and rare (7.1%) when absolute DAS level at 4 months was less than 1.6 and 3.6 or greater, respectively.

Study details: The study cohort included 772 consecutive patients with RA promptly treated with conventional DMARDs. Patients were classified into SDFR (n=149) and non-SDFR (n=623) groups.

Disclosures: The study was supported by the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Verstappen M et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02368-9.

Key clinical point: In anti-citrullinated protein antibodies (ACPA)-negative rheumatoid arthritis (RA), a significant decline in the disease activity score (DAS) within the first 4 months after diagnosis was associated with a higher probability of achieving sustained disease-modifying anti-rheumatic drugs (DMARDs)-free remission (SDFR).

Major finding: In patients with ACPA-negative RA, the decline in DAS within the first 4 months was stronger in the SDFR vs. non-SDFR group (−1.73 vs. −1.07 units; P less than .001). SDFR incidence was high (70.2%) and rare (7.1%) when absolute DAS level at 4 months was less than 1.6 and 3.6 or greater, respectively.

Study details: The study cohort included 772 consecutive patients with RA promptly treated with conventional DMARDs. Patients were classified into SDFR (n=149) and non-SDFR (n=623) groups.

Disclosures: The study was supported by the Dutch Arthritis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Verstappen M et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02368-9.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

rhnews@mdedge.com

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

rhnews@mdedge.com

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

rhnews@mdedge.com

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.