Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Key clinical point: Six biomarkers, including fine-specificity anti-citrullinated protein antibodies (ACPA) and anti-native protein antibodies, demonstrated a significant association with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and improved prediction sensitivity.

Major finding: Six fine-specificity antibody biomarkers, including immunoglobin G, to citrullinated (adjusted odds ratio [aOR] 3.47; 95% CI 1.71-7.01) and native (aOR 2.53; 95% CI 1.47-4.34) cyclic filaggrin 48-65 were associated with an increased risk for RA-ILD. Risk scores combining antibodies with clinical features with vs without biomarkers (score 5.9 vs 2.6) demonstrated higher sensitivity (67% vs 25%) and high specificity (≥93%) for developing RA-ILD at a threshold of 50% predicted probability.

Study details: This nested case-control study within an ongoing prospective registry included adult patients with incident RA-ILD (n = 84) and matched patients with RA without ILD (n = 233).

Disclosures: This study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Several authors reported ties with various sources unrelated to this study.

Source: Kronzer VL et al. Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: A nested case–control study. Lancet Rheumatol. 2023;5(2):E77-E87 (Feb). Doi: 10.1016/S2665-9913(22)00380-0

Key clinical point: Six biomarkers, including fine-specificity anti-citrullinated protein antibodies (ACPA) and anti-native protein antibodies, demonstrated a significant association with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and improved prediction sensitivity.

Major finding: Six fine-specificity antibody biomarkers, including immunoglobin G, to citrullinated (adjusted odds ratio [aOR] 3.47; 95% CI 1.71-7.01) and native (aOR 2.53; 95% CI 1.47-4.34) cyclic filaggrin 48-65 were associated with an increased risk for RA-ILD. Risk scores combining antibodies with clinical features with vs without biomarkers (score 5.9 vs 2.6) demonstrated higher sensitivity (67% vs 25%) and high specificity (≥93%) for developing RA-ILD at a threshold of 50% predicted probability.

Study details: This nested case-control study within an ongoing prospective registry included adult patients with incident RA-ILD (n = 84) and matched patients with RA without ILD (n = 233).

Disclosures: This study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Several authors reported ties with various sources unrelated to this study.

Source: Kronzer VL et al. Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: A nested case–control study. Lancet Rheumatol. 2023;5(2):E77-E87 (Feb). Doi: 10.1016/S2665-9913(22)00380-0

Key clinical point: Six biomarkers, including fine-specificity anti-citrullinated protein antibodies (ACPA) and anti-native protein antibodies, demonstrated a significant association with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and improved prediction sensitivity.

Major finding: Six fine-specificity antibody biomarkers, including immunoglobin G, to citrullinated (adjusted odds ratio [aOR] 3.47; 95% CI 1.71-7.01) and native (aOR 2.53; 95% CI 1.47-4.34) cyclic filaggrin 48-65 were associated with an increased risk for RA-ILD. Risk scores combining antibodies with clinical features with vs without biomarkers (score 5.9 vs 2.6) demonstrated higher sensitivity (67% vs 25%) and high specificity (≥93%) for developing RA-ILD at a threshold of 50% predicted probability.

Study details: This nested case-control study within an ongoing prospective registry included adult patients with incident RA-ILD (n = 84) and matched patients with RA without ILD (n = 233).

Disclosures: This study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Several authors reported ties with various sources unrelated to this study.

Source: Kronzer VL et al. Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: A nested case–control study. Lancet Rheumatol. 2023;5(2):E77-E87 (Feb). Doi: 10.1016/S2665-9913(22)00380-0

Key clinical point: The incidence of herpes zoster in the United States is nearly twice as high in patients with rheumatoid arthritis (RA) compared with those without RA, with the relative risk being higher among younger patients with RA than their older non-RA counterparts.

Major finding: The incidence of herpes zoster was significantly higher in patients with vs without RA (adjusted incidence rate ratio [aIRR] 1.93; P < .001) and younger patients (<50 years) with RA vs older individuals (≥50 years) without RA (aIRR 1.34; P < .001).

Study details: This retrospective, longitudinal cohort study included patients with (n = 67,650) and without RA (n = 11,401,743) without a prior diagnosis or vaccination for herpes zoster.

Disclosures: This study was funded by GlaxoSmithKline (GSK) Biologicals SA. Seven authors declared being employees of or shareholders in the GSK group of companies or a company funded by GSK. Two authors declared receiving grant support from the GSK group of companies or being a member of the American College of Rheumatology Vaccine Guideline Committee.

Source: Singer D et al. Incidence of Herpes Zoster in patients with rheumatoid arthritis in the United States: A retrospective cohort study. J Rheumatol. 2023 (Feb 1). Doi: 10.3899/jrheum.220986

Key clinical point: The incidence of herpes zoster in the United States is nearly twice as high in patients with rheumatoid arthritis (RA) compared with those without RA, with the relative risk being higher among younger patients with RA than their older non-RA counterparts.

Major finding: The incidence of herpes zoster was significantly higher in patients with vs without RA (adjusted incidence rate ratio [aIRR] 1.93; P < .001) and younger patients (<50 years) with RA vs older individuals (≥50 years) without RA (aIRR 1.34; P < .001).

Study details: This retrospective, longitudinal cohort study included patients with (n = 67,650) and without RA (n = 11,401,743) without a prior diagnosis or vaccination for herpes zoster.

Disclosures: This study was funded by GlaxoSmithKline (GSK) Biologicals SA. Seven authors declared being employees of or shareholders in the GSK group of companies or a company funded by GSK. Two authors declared receiving grant support from the GSK group of companies or being a member of the American College of Rheumatology Vaccine Guideline Committee.

Source: Singer D et al. Incidence of Herpes Zoster in patients with rheumatoid arthritis in the United States: A retrospective cohort study. J Rheumatol. 2023 (Feb 1). Doi: 10.3899/jrheum.220986

Key clinical point: The incidence of herpes zoster in the United States is nearly twice as high in patients with rheumatoid arthritis (RA) compared with those without RA, with the relative risk being higher among younger patients with RA than their older non-RA counterparts.

Major finding: The incidence of herpes zoster was significantly higher in patients with vs without RA (adjusted incidence rate ratio [aIRR] 1.93; P < .001) and younger patients (<50 years) with RA vs older individuals (≥50 years) without RA (aIRR 1.34; P < .001).

Study details: This retrospective, longitudinal cohort study included patients with (n = 67,650) and without RA (n = 11,401,743) without a prior diagnosis or vaccination for herpes zoster.

Disclosures: This study was funded by GlaxoSmithKline (GSK) Biologicals SA. Seven authors declared being employees of or shareholders in the GSK group of companies or a company funded by GSK. Two authors declared receiving grant support from the GSK group of companies or being a member of the American College of Rheumatology Vaccine Guideline Committee.

Source: Singer D et al. Incidence of Herpes Zoster in patients with rheumatoid arthritis in the United States: A retrospective cohort study. J Rheumatol. 2023 (Feb 1). Doi: 10.3899/jrheum.220986

Key clinical point: Smokers with a family history of rheumatoid arthritis (RA) may be considered a high-risk group who should be informed about increased smoking-associated RA risk and advised smoking cessation.

Major finding: Risk for RA was higher in individuals with vs without first-degree relatives affected with RA (adjusted hazard ratio [aHR] 4.49; 95% CI 3.96-5.10) and in current vs non-smokers (aHR 1.37; 95% CI 1.24-1.51), with the risk being markedly higher among smokers with a positive family history of RA (HR 6.44; 95% CI 4.61-9.00).

Study details: Findings are from a population-based cohort study that evaluated lifestyle factors and family relationships of 5,524,403 individuals with (n = 76,065) and without (n = 5,448,338) first-degree relatives affected with RA, of which 47,942 individuals developed RA.

Disclosures: This study was supported by the Chungbuk National University Korea National University Development Project. The authors declared no conflicts of interest.

Source: Kim HJ et al. Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study. Rheumatology (Oxford). 2023 (Jan 24). Doi: 10.1093/rheumatology/kead048

Key clinical point: Smokers with a family history of rheumatoid arthritis (RA) may be considered a high-risk group who should be informed about increased smoking-associated RA risk and advised smoking cessation.

Major finding: Risk for RA was higher in individuals with vs without first-degree relatives affected with RA (adjusted hazard ratio [aHR] 4.49; 95% CI 3.96-5.10) and in current vs non-smokers (aHR 1.37; 95% CI 1.24-1.51), with the risk being markedly higher among smokers with a positive family history of RA (HR 6.44; 95% CI 4.61-9.00).

Study details: Findings are from a population-based cohort study that evaluated lifestyle factors and family relationships of 5,524,403 individuals with (n = 76,065) and without (n = 5,448,338) first-degree relatives affected with RA, of which 47,942 individuals developed RA.

Disclosures: This study was supported by the Chungbuk National University Korea National University Development Project. The authors declared no conflicts of interest.

Source: Kim HJ et al. Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study. Rheumatology (Oxford). 2023 (Jan 24). Doi: 10.1093/rheumatology/kead048

Key clinical point: Smokers with a family history of rheumatoid arthritis (RA) may be considered a high-risk group who should be informed about increased smoking-associated RA risk and advised smoking cessation.

Major finding: Risk for RA was higher in individuals with vs without first-degree relatives affected with RA (adjusted hazard ratio [aHR] 4.49; 95% CI 3.96-5.10) and in current vs non-smokers (aHR 1.37; 95% CI 1.24-1.51), with the risk being markedly higher among smokers with a positive family history of RA (HR 6.44; 95% CI 4.61-9.00).

Study details: Findings are from a population-based cohort study that evaluated lifestyle factors and family relationships of 5,524,403 individuals with (n = 76,065) and without (n = 5,448,338) first-degree relatives affected with RA, of which 47,942 individuals developed RA.

Disclosures: This study was supported by the Chungbuk National University Korea National University Development Project. The authors declared no conflicts of interest.

Source: Kim HJ et al. Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study. Rheumatology (Oxford). 2023 (Jan 24). Doi: 10.1093/rheumatology/kead048

Key clinical point: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains rare; treatment strategies have diversified over years, but high demand for analgesics and opioids suggests unmet needs in pain management.

Major finding: Between 2007 and 2020, the prevalence and incidence of ILD among patients with RA were 1.6%-2.2% and 0.13%-0.21% per year, respectively, and biologic disease-modifying antirheumatic drug (DMARD) use increased from 16% to 24%, whereas glucocorticoid, conventional synthetic DMARD, and nonsteroidal anti-inflammatory drug use declined from 84% to 68%, 83% to 55%, and 62% to 38%, respectively. However, analgesic use increased and ≈30% of patients received opioids.

Study details: This study analyzed insurance claims data of 98,435 and 142,657 patients diagnosed with RA, 257 and 1484 with prevalent ILD, and 18 and 90 with incident ILD in 2007 and 2020, respectively.

Disclosures: This study was supported by the German Federal Ministry of Education and Research within the Targeted Risk Management in Musculoskeletal Diseases network (TARISMA). Two authors declared receiving speaker fees from various sources outside this study.

Source: Albrecht K et al. Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020. RMD Open. 2023;9:e002777 (Jan 20). Doi: 10.1136/rmdopen-2022-002777

Key clinical point: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains rare; treatment strategies have diversified over years, but high demand for analgesics and opioids suggests unmet needs in pain management.

Major finding: Between 2007 and 2020, the prevalence and incidence of ILD among patients with RA were 1.6%-2.2% and 0.13%-0.21% per year, respectively, and biologic disease-modifying antirheumatic drug (DMARD) use increased from 16% to 24%, whereas glucocorticoid, conventional synthetic DMARD, and nonsteroidal anti-inflammatory drug use declined from 84% to 68%, 83% to 55%, and 62% to 38%, respectively. However, analgesic use increased and ≈30% of patients received opioids.

Study details: This study analyzed insurance claims data of 98,435 and 142,657 patients diagnosed with RA, 257 and 1484 with prevalent ILD, and 18 and 90 with incident ILD in 2007 and 2020, respectively.

Disclosures: This study was supported by the German Federal Ministry of Education and Research within the Targeted Risk Management in Musculoskeletal Diseases network (TARISMA). Two authors declared receiving speaker fees from various sources outside this study.

Source: Albrecht K et al. Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020. RMD Open. 2023;9:e002777 (Jan 20). Doi: 10.1136/rmdopen-2022-002777

Key clinical point: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains rare; treatment strategies have diversified over years, but high demand for analgesics and opioids suggests unmet needs in pain management.

Major finding: Between 2007 and 2020, the prevalence and incidence of ILD among patients with RA were 1.6%-2.2% and 0.13%-0.21% per year, respectively, and biologic disease-modifying antirheumatic drug (DMARD) use increased from 16% to 24%, whereas glucocorticoid, conventional synthetic DMARD, and nonsteroidal anti-inflammatory drug use declined from 84% to 68%, 83% to 55%, and 62% to 38%, respectively. However, analgesic use increased and ≈30% of patients received opioids.

Study details: This study analyzed insurance claims data of 98,435 and 142,657 patients diagnosed with RA, 257 and 1484 with prevalent ILD, and 18 and 90 with incident ILD in 2007 and 2020, respectively.

Disclosures: This study was supported by the German Federal Ministry of Education and Research within the Targeted Risk Management in Musculoskeletal Diseases network (TARISMA). Two authors declared receiving speaker fees from various sources outside this study.

Source: Albrecht K et al. Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020. RMD Open. 2023;9:e002777 (Jan 20). Doi: 10.1136/rmdopen-2022-002777

Key clinical point: A strict approach toward treat-to-target (T2T) management did not reduce radiographic progression in a daily practice cohort of patients with active rheumatoid arthritis (RA) compared with a relatively lenient approach toward T2T.

Major finding: A T2T approach in a 3-month interval failed to reduce radiographic progression in the same 6-month period with 2 vs 0 visits (change in Sharp-van der Heijde score [Δ] 0.15 units; 95% CI −0.04 to 0.33) and 1 vs 0 visits (Δ 0.08 units; 95% CI −0.06 to 0.22) after T2T.

Study details: This longitudinal analysis of a 2-year prospective observational study cohort included 521 patients with active RA who started or changed conventional synthetic or biologic disease-modifying antirheumatic drugs and underwent treatment intensification according to the T2T approach.

Disclosures: The BIODAM study was supported by an unrestricted grant from AbbVie. Several authors reported receiving research grants, consulting fees, honoraria, or an unrestricted educational grant from various sources, including AbbVie.

Source: Ramiro S et al. Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM. Rheumatology (Oxford). 2023 (Jan 16). Doi:10.1093/rheumatology/kead021

Key clinical point: A strict approach toward treat-to-target (T2T) management did not reduce radiographic progression in a daily practice cohort of patients with active rheumatoid arthritis (RA) compared with a relatively lenient approach toward T2T.

Major finding: A T2T approach in a 3-month interval failed to reduce radiographic progression in the same 6-month period with 2 vs 0 visits (change in Sharp-van der Heijde score [Δ] 0.15 units; 95% CI −0.04 to 0.33) and 1 vs 0 visits (Δ 0.08 units; 95% CI −0.06 to 0.22) after T2T.

Study details: This longitudinal analysis of a 2-year prospective observational study cohort included 521 patients with active RA who started or changed conventional synthetic or biologic disease-modifying antirheumatic drugs and underwent treatment intensification according to the T2T approach.

Disclosures: The BIODAM study was supported by an unrestricted grant from AbbVie. Several authors reported receiving research grants, consulting fees, honoraria, or an unrestricted educational grant from various sources, including AbbVie.

Source: Ramiro S et al. Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM. Rheumatology (Oxford). 2023 (Jan 16). Doi:10.1093/rheumatology/kead021

Key clinical point: A strict approach toward treat-to-target (T2T) management did not reduce radiographic progression in a daily practice cohort of patients with active rheumatoid arthritis (RA) compared with a relatively lenient approach toward T2T.

Major finding: A T2T approach in a 3-month interval failed to reduce radiographic progression in the same 6-month period with 2 vs 0 visits (change in Sharp-van der Heijde score [Δ] 0.15 units; 95% CI −0.04 to 0.33) and 1 vs 0 visits (Δ 0.08 units; 95% CI −0.06 to 0.22) after T2T.

Study details: This longitudinal analysis of a 2-year prospective observational study cohort included 521 patients with active RA who started or changed conventional synthetic or biologic disease-modifying antirheumatic drugs and underwent treatment intensification according to the T2T approach.

Disclosures: The BIODAM study was supported by an unrestricted grant from AbbVie. Several authors reported receiving research grants, consulting fees, honoraria, or an unrestricted educational grant from various sources, including AbbVie.

Source: Ramiro S et al. Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM. Rheumatology (Oxford). 2023 (Jan 16). Doi:10.1093/rheumatology/kead021

Key clinical point: Rheumatoid arthritis (RA) is associated with a high risk for end-stage renal disease, with the risk being prominent among relatively young and comorbidity-free individuals and those who consume alcohol.

Major finding: Patients with RA were at a significantly higher risk for end-stage renal disease compared with those without RA (adjusted hazard ratio 2.153; 95% CI 1.948-2.379), particularly among patients who were relatively young (P_interaction < .001), those without comorbidities (P_interaction < .001), and those who consumed alcohol (P_interaction  =  .021).

Study details: This retrospective population-based study included 154,997 patients with RA and 774,985 age- and sex-matched individuals without RA.

Disclosures: This study was supported by grants from the Chonnam National University Hospital Biomedical Research Institute and National Research Foundation of Korea, funded by the Korea Government. The authors declared no conflicts of interest.

Source: Suh SH et al. Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study. Front Med (Lausanne). 2023;10:1116489 (Feb 2). Doi: 10.3389/fmed.2023.1116489

Key clinical point: Rheumatoid arthritis (RA) is associated with a high risk for end-stage renal disease, with the risk being prominent among relatively young and comorbidity-free individuals and those who consume alcohol.

Major finding: Patients with RA were at a significantly higher risk for end-stage renal disease compared with those without RA (adjusted hazard ratio 2.153; 95% CI 1.948-2.379), particularly among patients who were relatively young (P_interaction < .001), those without comorbidities (P_interaction < .001), and those who consumed alcohol (P_interaction  =  .021).

Study details: This retrospective population-based study included 154,997 patients with RA and 774,985 age- and sex-matched individuals without RA.

Disclosures: This study was supported by grants from the Chonnam National University Hospital Biomedical Research Institute and National Research Foundation of Korea, funded by the Korea Government. The authors declared no conflicts of interest.

Source: Suh SH et al. Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study. Front Med (Lausanne). 2023;10:1116489 (Feb 2). Doi: 10.3389/fmed.2023.1116489

Key clinical point: Rheumatoid arthritis (RA) is associated with a high risk for end-stage renal disease, with the risk being prominent among relatively young and comorbidity-free individuals and those who consume alcohol.

Major finding: Patients with RA were at a significantly higher risk for end-stage renal disease compared with those without RA (adjusted hazard ratio 2.153; 95% CI 1.948-2.379), particularly among patients who were relatively young (P_interaction < .001), those without comorbidities (P_interaction < .001), and those who consumed alcohol (P_interaction  =  .021).

Study details: This retrospective population-based study included 154,997 patients with RA and 774,985 age- and sex-matched individuals without RA.

Disclosures: This study was supported by grants from the Chonnam National University Hospital Biomedical Research Institute and National Research Foundation of Korea, funded by the Korea Government. The authors declared no conflicts of interest.

Source: Suh SH et al. Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study. Front Med (Lausanne). 2023;10:1116489 (Feb 2). Doi: 10.3389/fmed.2023.1116489

Key clinical point: Pregnant women with vs without rheumatoid arthritis (RA) and their infants should be closely monitored prenatally and during the year after delivery as they are at a higher risk for rehospitalization within 2 years and more likely to require intensive prenatal or neonatal care.

Major finding: Women with vs without RA required more intensive prenatal care (adjusted relative risk [aRR] 1.46; 95% CI 1.33-1.60) and had a higher risk for postpartum non-pregnancy rehospitalization <2 years after delivery (aRR 1.33; 95% CI 1.13-1.56). Infants of women with vs without RA had a higher risk for neonatal intensive care unit admission (aRR 1.89; 95% CI 1.56-2.30) and rehospitalization <2 years after birth (aRR 1.22; 95% CI 1.01-1.46).

Study details: This population-based retrospective cohort study included pregnant women with (n = 1223) and without (n = 12,293) RA and those with (n = 1354) and without (n = 13,751) systemic lupus erythematosus.

Disclosures: This study was funded by Eunice Kennedy Shriver National Institute of Child Health & Human Development, US National Institutes of Health. The authors did not report conflicts of interest.

Source: Singh N et al. Birth outcomes and re-hospitalizations among pregnant women with rheumatoid arthritis and systemic lupus erythematosus and their offspring. Arthritis Care Res (Hoboken). 2023 (Jan 10). Doi: 10.1002/acr.25087

Key clinical point: Pregnant women with vs without rheumatoid arthritis (RA) and their infants should be closely monitored prenatally and during the year after delivery as they are at a higher risk for rehospitalization within 2 years and more likely to require intensive prenatal or neonatal care.

Major finding: Women with vs without RA required more intensive prenatal care (adjusted relative risk [aRR] 1.46; 95% CI 1.33-1.60) and had a higher risk for postpartum non-pregnancy rehospitalization <2 years after delivery (aRR 1.33; 95% CI 1.13-1.56). Infants of women with vs without RA had a higher risk for neonatal intensive care unit admission (aRR 1.89; 95% CI 1.56-2.30) and rehospitalization <2 years after birth (aRR 1.22; 95% CI 1.01-1.46).

Study details: This population-based retrospective cohort study included pregnant women with (n = 1223) and without (n = 12,293) RA and those with (n = 1354) and without (n = 13,751) systemic lupus erythematosus.

Disclosures: This study was funded by Eunice Kennedy Shriver National Institute of Child Health & Human Development, US National Institutes of Health. The authors did not report conflicts of interest.

Source: Singh N et al. Birth outcomes and re-hospitalizations among pregnant women with rheumatoid arthritis and systemic lupus erythematosus and their offspring. Arthritis Care Res (Hoboken). 2023 (Jan 10). Doi: 10.1002/acr.25087

Key clinical point: Pregnant women with vs without rheumatoid arthritis (RA) and their infants should be closely monitored prenatally and during the year after delivery as they are at a higher risk for rehospitalization within 2 years and more likely to require intensive prenatal or neonatal care.

Major finding: Women with vs without RA required more intensive prenatal care (adjusted relative risk [aRR] 1.46; 95% CI 1.33-1.60) and had a higher risk for postpartum non-pregnancy rehospitalization <2 years after delivery (aRR 1.33; 95% CI 1.13-1.56). Infants of women with vs without RA had a higher risk for neonatal intensive care unit admission (aRR 1.89; 95% CI 1.56-2.30) and rehospitalization <2 years after birth (aRR 1.22; 95% CI 1.01-1.46).

Study details: This population-based retrospective cohort study included pregnant women with (n = 1223) and without (n = 12,293) RA and those with (n = 1354) and without (n = 13,751) systemic lupus erythematosus.

Disclosures: This study was funded by Eunice Kennedy Shriver National Institute of Child Health & Human Development, US National Institutes of Health. The authors did not report conflicts of interest.

Source: Singh N et al. Birth outcomes and re-hospitalizations among pregnant women with rheumatoid arthritis and systemic lupus erythematosus and their offspring. Arthritis Care Res (Hoboken). 2023 (Jan 10). Doi: 10.1002/acr.25087

Key clinical point: Patients with early rheumatoid arthritis (ERA) receiving treat-to-target management did not have an excess 5-year risk for cardiovascular events (CVE) compared with risk factor-matched non-RA control individuals.

Major finding: Over 5 years, the risk for incident CVE was comparable among patients with ERA and matched non-RA control individuals (hazard ratio [HR] 0.53; P  =  .3), but significantly higher among patients with historical RA (HRA) receiving routine care vs matched non-RA control individuals (HR 1.95; P  =  .009).

Study details: The data come from an observational case-control study including patients with ERA (n = 261) receiving treat-to-target management and patients with HRA (n = 268) receiving routine care, each of whom were cardiovascular risk factor-matched to 3 non-RA control individuals.

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

Source: Lam TO et al. Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: A case-control study. Rheumatology (Oxford). 2023 (Jan 27). Doi: 10.1093/rheumatology/kead039

Key clinical point: Patients with early rheumatoid arthritis (ERA) receiving treat-to-target management did not have an excess 5-year risk for cardiovascular events (CVE) compared with risk factor-matched non-RA control individuals.

Major finding: Over 5 years, the risk for incident CVE was comparable among patients with ERA and matched non-RA control individuals (hazard ratio [HR] 0.53; P  =  .3), but significantly higher among patients with historical RA (HRA) receiving routine care vs matched non-RA control individuals (HR 1.95; P  =  .009).

Study details: The data come from an observational case-control study including patients with ERA (n = 261) receiving treat-to-target management and patients with HRA (n = 268) receiving routine care, each of whom were cardiovascular risk factor-matched to 3 non-RA control individuals.

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

Source: Lam TO et al. Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: A case-control study. Rheumatology (Oxford). 2023 (Jan 27). Doi: 10.1093/rheumatology/kead039

Key clinical point: Patients with early rheumatoid arthritis (ERA) receiving treat-to-target management did not have an excess 5-year risk for cardiovascular events (CVE) compared with risk factor-matched non-RA control individuals.

Major finding: Over 5 years, the risk for incident CVE was comparable among patients with ERA and matched non-RA control individuals (hazard ratio [HR] 0.53; P  =  .3), but significantly higher among patients with historical RA (HRA) receiving routine care vs matched non-RA control individuals (HR 1.95; P  =  .009).

Study details: The data come from an observational case-control study including patients with ERA (n = 261) receiving treat-to-target management and patients with HRA (n = 268) receiving routine care, each of whom were cardiovascular risk factor-matched to 3 non-RA control individuals.

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

Source: Lam TO et al. Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: A case-control study. Rheumatology (Oxford). 2023 (Jan 27). Doi: 10.1093/rheumatology/kead039

Key clinical point: The risk for bacterial infections significantly increased with concomitant use of methotrexate and glucocorticoids in patients with rheumatoid arthritis (RA) who were receiving biologic disease-modifying antirheumatic drugs (bDMARD), especially when the doses of concomitant methotrexate and glucocorticoids were ≥8 mg/week and ≥5 mg/day, respectively.

Major finding: Overall, the incidence of bacterial infections was 16.8%, with the highest incidence (25.5%) observed in patients receiving combination therapy with methotrexate (≥8 mg/week) and glucocorticoids (≥5 mg/day). Co-prescription of ≥5 mg/day glucocorticoids with an increasing methotrexate dose (P  =  .013) and ≥8 mg/week methotrexate with an increasing glucocorticoid dose (P  =  .009) significantly increased the risk for bacterial infections.

Study details: This retrospective cohort study included 2837 patients with RA who initiated bDMARD with concomitant conventional synthetic DMARD, methotrexate, or oral glucocorticoids.

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

Source: Ota R et al. Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study. Br J Clin Pharmacol. 2023 (Feb 8). Doi: 10.1111/bcp.15687

Key clinical point: The risk for bacterial infections significantly increased with concomitant use of methotrexate and glucocorticoids in patients with rheumatoid arthritis (RA) who were receiving biologic disease-modifying antirheumatic drugs (bDMARD), especially when the doses of concomitant methotrexate and glucocorticoids were ≥8 mg/week and ≥5 mg/day, respectively.

Major finding: Overall, the incidence of bacterial infections was 16.8%, with the highest incidence (25.5%) observed in patients receiving combination therapy with methotrexate (≥8 mg/week) and glucocorticoids (≥5 mg/day). Co-prescription of ≥5 mg/day glucocorticoids with an increasing methotrexate dose (P  =  .013) and ≥8 mg/week methotrexate with an increasing glucocorticoid dose (P  =  .009) significantly increased the risk for bacterial infections.

Study details: This retrospective cohort study included 2837 patients with RA who initiated bDMARD with concomitant conventional synthetic DMARD, methotrexate, or oral glucocorticoids.

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

Source: Ota R et al. Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study. Br J Clin Pharmacol. 2023 (Feb 8). Doi: 10.1111/bcp.15687

Key clinical point: The risk for bacterial infections significantly increased with concomitant use of methotrexate and glucocorticoids in patients with rheumatoid arthritis (RA) who were receiving biologic disease-modifying antirheumatic drugs (bDMARD), especially when the doses of concomitant methotrexate and glucocorticoids were ≥8 mg/week and ≥5 mg/day, respectively.

Major finding: Overall, the incidence of bacterial infections was 16.8%, with the highest incidence (25.5%) observed in patients receiving combination therapy with methotrexate (≥8 mg/week) and glucocorticoids (≥5 mg/day). Co-prescription of ≥5 mg/day glucocorticoids with an increasing methotrexate dose (P  =  .013) and ≥8 mg/week methotrexate with an increasing glucocorticoid dose (P  =  .009) significantly increased the risk for bacterial infections.

Study details: This retrospective cohort study included 2837 patients with RA who initiated bDMARD with concomitant conventional synthetic DMARD, methotrexate, or oral glucocorticoids.

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

Source: Ota R et al. Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study. Br J Clin Pharmacol. 2023 (Feb 8). Doi: 10.1111/bcp.15687