Rheumatoid arthritis: Five things to know

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.