Rheumatoid Arthritis

Key clinical point: Tumor necrosis factor inhibitors (TNFi) increased the risk for septic arthritis in patients with seropositive rheumatoid arthritis (RA), with higher incidences within 1 year of initiating TNFi.

Major finding: Patients with seropositive RA treated with infliximab (adjusted hazard ratio [aHR] 2.37), etanercept (aHR 1.82), or adalimumab/golimumab (aHR 1.82; all P < .01) were prone to develop septic arthritis, with the incidence being higher within 1 year of initiating TNFi (incidence rate/1000 person-year 25.51).

Study details: This retrospective study included 145,129 patients with new-onset seropositive RA or ankylosing spondylitis, of which 1170 patients developed septic arthritis.

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

Source: Kim HW et al. Incidence of septic arthritis in patients with ankylosing spondylitis and seropositive rheumatoid arthritis following TNF-inhibitor therapy. Rheumatology (Oxford). 2022 (Dec 23). Doi: 10.1093/rheumatology/keac721

Key clinical point: Tumor necrosis factor inhibitors (TNFi) increased the risk for septic arthritis in patients with seropositive rheumatoid arthritis (RA), with higher incidences within 1 year of initiating TNFi.

Major finding: Patients with seropositive RA treated with infliximab (adjusted hazard ratio [aHR] 2.37), etanercept (aHR 1.82), or adalimumab/golimumab (aHR 1.82; all P < .01) were prone to develop septic arthritis, with the incidence being higher within 1 year of initiating TNFi (incidence rate/1000 person-year 25.51).

Study details: This retrospective study included 145,129 patients with new-onset seropositive RA or ankylosing spondylitis, of which 1170 patients developed septic arthritis.

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

Source: Kim HW et al. Incidence of septic arthritis in patients with ankylosing spondylitis and seropositive rheumatoid arthritis following TNF-inhibitor therapy. Rheumatology (Oxford). 2022 (Dec 23). Doi: 10.1093/rheumatology/keac721

Key clinical point: Tumor necrosis factor inhibitors (TNFi) increased the risk for septic arthritis in patients with seropositive rheumatoid arthritis (RA), with higher incidences within 1 year of initiating TNFi.

Major finding: Patients with seropositive RA treated with infliximab (adjusted hazard ratio [aHR] 2.37), etanercept (aHR 1.82), or adalimumab/golimumab (aHR 1.82; all P < .01) were prone to develop septic arthritis, with the incidence being higher within 1 year of initiating TNFi (incidence rate/1000 person-year 25.51).

Study details: This retrospective study included 145,129 patients with new-onset seropositive RA or ankylosing spondylitis, of which 1170 patients developed septic arthritis.

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

Source: Kim HW et al. Incidence of septic arthritis in patients with ankylosing spondylitis and seropositive rheumatoid arthritis following TNF-inhibitor therapy. Rheumatology (Oxford). 2022 (Dec 23). Doi: 10.1093/rheumatology/keac721

Key clinical point: Cumulative local joint inflammation over time was significantly associated with radiographic joint damage progression in the same joint in patients with early rheumatoid arthritis (RA) who were treated to a target disease activity score (DAS) of ≤2.4 for 10 years.

Major finding: Cumulative joint swelling was positively associated with local joint damage progression in the same joint (β 0.14; 95% CI 0.13-0.15). Each additional visit for joint swelling increased the joint damage score by a 0.13 unit and frequency of joint swelling in same vs other joints better predicted local joint damage progression (P < .001).

Study details: This post hoc analysis of the BeSt study included 473 patients with early RA who were randomly assigned to receive sequential monotherapy, step-up combination therapy, or initial combination therapy with methotrexate with or without sulfasalazine+prednisone or infliximab, with treatment intensification every 3 months until DAS ≤2.4 was achieved.

Disclosures: The BeSt study received funding from the Dutch College of Health Insurances and others. No competing interests were declared.

Source: Heckert SL et al. Frequency of joint inflammation is associated with local joint damage progression in rheumatoid arthritis despite long-term targeted treatment. RMD Open. 2023;9(1):e002552 (Jan 6). Doi: 10.1136/rmdopen-2022-002552

Key clinical point: Cumulative local joint inflammation over time was significantly associated with radiographic joint damage progression in the same joint in patients with early rheumatoid arthritis (RA) who were treated to a target disease activity score (DAS) of ≤2.4 for 10 years.

Major finding: Cumulative joint swelling was positively associated with local joint damage progression in the same joint (β 0.14; 95% CI 0.13-0.15). Each additional visit for joint swelling increased the joint damage score by a 0.13 unit and frequency of joint swelling in same vs other joints better predicted local joint damage progression (P < .001).

Study details: This post hoc analysis of the BeSt study included 473 patients with early RA who were randomly assigned to receive sequential monotherapy, step-up combination therapy, or initial combination therapy with methotrexate with or without sulfasalazine+prednisone or infliximab, with treatment intensification every 3 months until DAS ≤2.4 was achieved.

Disclosures: The BeSt study received funding from the Dutch College of Health Insurances and others. No competing interests were declared.

Source: Heckert SL et al. Frequency of joint inflammation is associated with local joint damage progression in rheumatoid arthritis despite long-term targeted treatment. RMD Open. 2023;9(1):e002552 (Jan 6). Doi: 10.1136/rmdopen-2022-002552

Key clinical point: Cumulative local joint inflammation over time was significantly associated with radiographic joint damage progression in the same joint in patients with early rheumatoid arthritis (RA) who were treated to a target disease activity score (DAS) of ≤2.4 for 10 years.

Major finding: Cumulative joint swelling was positively associated with local joint damage progression in the same joint (β 0.14; 95% CI 0.13-0.15). Each additional visit for joint swelling increased the joint damage score by a 0.13 unit and frequency of joint swelling in same vs other joints better predicted local joint damage progression (P < .001).

Study details: This post hoc analysis of the BeSt study included 473 patients with early RA who were randomly assigned to receive sequential monotherapy, step-up combination therapy, or initial combination therapy with methotrexate with or without sulfasalazine+prednisone or infliximab, with treatment intensification every 3 months until DAS ≤2.4 was achieved.

Disclosures: The BeSt study received funding from the Dutch College of Health Insurances and others. No competing interests were declared.

Source: Heckert SL et al. Frequency of joint inflammation is associated with local joint damage progression in rheumatoid arthritis despite long-term targeted treatment. RMD Open. 2023;9(1):e002552 (Jan 6). Doi: 10.1136/rmdopen-2022-002552

Key clinical point: “Plants for Joints” (PFJ), a 16-week multidisciplinary lifestyle program based on whole food plant-based diet, physical activity, and stress management in addition to usual care, significantly improved disease activity compared with usual care alone in patients with rheumatoid arthritis (RA) and low-to-moderate disease activity.

Major finding: After 16 weeks, patients receiving PFJ vs usual care alone had a greater reduction in disease activity score of 28 joints (DAS28; mean difference −0.90; P < .0001) and were more likely to achieve DAS28 <2.60 (odds ratio [OR] 4.6) and European Alliance of Associations for Rheumatology Good Response (OR 4.3; both P < .001). No serious adverse events were reported.

Study details: This randomized controlled trial, “Plants for Joints,” included 77 patients with RA and low-to-moderate disease activity who were randomly assigned to receive PFJ intervention plus usual care or usual care alone.

Disclosures: The trial was funded by Reade (The Netherlands) and other sources. The authors declared no conflicts of interest.

Source: Walrabenstein W et al. A multidisciplinary lifestyle program for rheumatoid arthritis: The “Plants for Joints” randomized controlled trial. Rheumatology (Oxford). 2023 (Jan 6). Doi: 10.1093/rheumatology/keac693

Key clinical point: “Plants for Joints” (PFJ), a 16-week multidisciplinary lifestyle program based on whole food plant-based diet, physical activity, and stress management in addition to usual care, significantly improved disease activity compared with usual care alone in patients with rheumatoid arthritis (RA) and low-to-moderate disease activity.

Major finding: After 16 weeks, patients receiving PFJ vs usual care alone had a greater reduction in disease activity score of 28 joints (DAS28; mean difference −0.90; P < .0001) and were more likely to achieve DAS28 <2.60 (odds ratio [OR] 4.6) and European Alliance of Associations for Rheumatology Good Response (OR 4.3; both P < .001). No serious adverse events were reported.

Study details: This randomized controlled trial, “Plants for Joints,” included 77 patients with RA and low-to-moderate disease activity who were randomly assigned to receive PFJ intervention plus usual care or usual care alone.

Disclosures: The trial was funded by Reade (The Netherlands) and other sources. The authors declared no conflicts of interest.

Source: Walrabenstein W et al. A multidisciplinary lifestyle program for rheumatoid arthritis: The “Plants for Joints” randomized controlled trial. Rheumatology (Oxford). 2023 (Jan 6). Doi: 10.1093/rheumatology/keac693

Key clinical point: “Plants for Joints” (PFJ), a 16-week multidisciplinary lifestyle program based on whole food plant-based diet, physical activity, and stress management in addition to usual care, significantly improved disease activity compared with usual care alone in patients with rheumatoid arthritis (RA) and low-to-moderate disease activity.

Major finding: After 16 weeks, patients receiving PFJ vs usual care alone had a greater reduction in disease activity score of 28 joints (DAS28; mean difference −0.90; P < .0001) and were more likely to achieve DAS28 <2.60 (odds ratio [OR] 4.6) and European Alliance of Associations for Rheumatology Good Response (OR 4.3; both P < .001). No serious adverse events were reported.

Study details: This randomized controlled trial, “Plants for Joints,” included 77 patients with RA and low-to-moderate disease activity who were randomly assigned to receive PFJ intervention plus usual care or usual care alone.

Disclosures: The trial was funded by Reade (The Netherlands) and other sources. The authors declared no conflicts of interest.

Source: Walrabenstein W et al. A multidisciplinary lifestyle program for rheumatoid arthritis: The “Plants for Joints” randomized controlled trial. Rheumatology (Oxford). 2023 (Jan 6). Doi: 10.1093/rheumatology/keac693

Key clinical point: Tapering glucocorticoids to doses >2.5 mg/day was effective with no increase in the risk for flare, whereas tapering to doses ≤2.5 mg/day significantly increased the risk for flare in patients with rheumatoid arthritis (RA) receiving biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Discontinuation of glucocorticoids (adjusted odds ratio [aOR] 1.45; 95% CI 1.13-2.24) and tapering of glucocorticoid dose to 0-2.5 mg/day (aOR 1.37; 95% CI 1.06-2.01) were significantly associated with an increased risk for flare, whereas tapering of glucocorticoid dose to >2.5 mg/day did not significantly increase the risk for flare compared with no tapering.

Study details: The data come from a case-crossover study including 508 patients with RA receiving bDMARD with or without glucocorticoids, of which 52.5% of patients reported at least one flare.

Disclosures: This study did not declare any specific funding. No conflicts of interest were declared.

Source: Adami G et al. Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs). RMD Open. 2023;9(1):e002792 (Jan 4). Doi: 10.1136/rmdopen-2022-002792

Key clinical point: Tapering glucocorticoids to doses >2.5 mg/day was effective with no increase in the risk for flare, whereas tapering to doses ≤2.5 mg/day significantly increased the risk for flare in patients with rheumatoid arthritis (RA) receiving biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Discontinuation of glucocorticoids (adjusted odds ratio [aOR] 1.45; 95% CI 1.13-2.24) and tapering of glucocorticoid dose to 0-2.5 mg/day (aOR 1.37; 95% CI 1.06-2.01) were significantly associated with an increased risk for flare, whereas tapering of glucocorticoid dose to >2.5 mg/day did not significantly increase the risk for flare compared with no tapering.

Study details: The data come from a case-crossover study including 508 patients with RA receiving bDMARD with or without glucocorticoids, of which 52.5% of patients reported at least one flare.

Disclosures: This study did not declare any specific funding. No conflicts of interest were declared.

Source: Adami G et al. Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs). RMD Open. 2023;9(1):e002792 (Jan 4). Doi: 10.1136/rmdopen-2022-002792

Key clinical point: Tapering glucocorticoids to doses >2.5 mg/day was effective with no increase in the risk for flare, whereas tapering to doses ≤2.5 mg/day significantly increased the risk for flare in patients with rheumatoid arthritis (RA) receiving biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Discontinuation of glucocorticoids (adjusted odds ratio [aOR] 1.45; 95% CI 1.13-2.24) and tapering of glucocorticoid dose to 0-2.5 mg/day (aOR 1.37; 95% CI 1.06-2.01) were significantly associated with an increased risk for flare, whereas tapering of glucocorticoid dose to >2.5 mg/day did not significantly increase the risk for flare compared with no tapering.

Study details: The data come from a case-crossover study including 508 patients with RA receiving bDMARD with or without glucocorticoids, of which 52.5% of patients reported at least one flare.

Disclosures: This study did not declare any specific funding. No conflicts of interest were declared.

Source: Adami G et al. Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs). RMD Open. 2023;9(1):e002792 (Jan 4). Doi: 10.1136/rmdopen-2022-002792

Key clinical point: Patients with rheumatoid arthritis (RA) who were males or had multiple comorbidities were less likely to achieve quality care markers, thereby highlighting the need to prioritize early treatment in the vulnerable patient population.

Major finding: Among patients with RA, males (odds ratio [OR] 0.72; 95% CI 0.72-0.73) and those with a Rheumatic Disease Comorbidity Index >2 (OR 0.88; 95% CI 0.86-0.90) were less likely to receive a rheumatologist referral, with findings being similar for annual physical examination. Additionally, the presence of diabetes was associated with reduced odds of receiving a rheumatologist referral (OR 0.77; 95% CI 0.76-0.78) or annual physical examination (OR 0.59; 95% CI 0.56-0.62).

Study details: This retrospective observational cohort study included 581,770 patients with incident RA.

Disclosures: This study was funded by joint grants from Chang Gung Memorial Hospital-University of Michigan Medical Center to two authors. KC Chung reported receiving funding, research grant, and book royalties from various sources.

Source: Seyferth AV et al. Factors associated with quality care among adults with rheumatoid arthritis. JAMA Netw Open. 2022;5(12):e2246299 (Dec 12). Doi: 10.1001/jamanetworkopen.2022.46299.

Key clinical point: Patients with rheumatoid arthritis (RA) who were males or had multiple comorbidities were less likely to achieve quality care markers, thereby highlighting the need to prioritize early treatment in the vulnerable patient population.

Major finding: Among patients with RA, males (odds ratio [OR] 0.72; 95% CI 0.72-0.73) and those with a Rheumatic Disease Comorbidity Index >2 (OR 0.88; 95% CI 0.86-0.90) were less likely to receive a rheumatologist referral, with findings being similar for annual physical examination. Additionally, the presence of diabetes was associated with reduced odds of receiving a rheumatologist referral (OR 0.77; 95% CI 0.76-0.78) or annual physical examination (OR 0.59; 95% CI 0.56-0.62).

Study details: This retrospective observational cohort study included 581,770 patients with incident RA.

Disclosures: This study was funded by joint grants from Chang Gung Memorial Hospital-University of Michigan Medical Center to two authors. KC Chung reported receiving funding, research grant, and book royalties from various sources.

Source: Seyferth AV et al. Factors associated with quality care among adults with rheumatoid arthritis. JAMA Netw Open. 2022;5(12):e2246299 (Dec 12). Doi: 10.1001/jamanetworkopen.2022.46299.

Key clinical point: Patients with rheumatoid arthritis (RA) who were males or had multiple comorbidities were less likely to achieve quality care markers, thereby highlighting the need to prioritize early treatment in the vulnerable patient population.

Major finding: Among patients with RA, males (odds ratio [OR] 0.72; 95% CI 0.72-0.73) and those with a Rheumatic Disease Comorbidity Index >2 (OR 0.88; 95% CI 0.86-0.90) were less likely to receive a rheumatologist referral, with findings being similar for annual physical examination. Additionally, the presence of diabetes was associated with reduced odds of receiving a rheumatologist referral (OR 0.77; 95% CI 0.76-0.78) or annual physical examination (OR 0.59; 95% CI 0.56-0.62).

Study details: This retrospective observational cohort study included 581,770 patients with incident RA.

Disclosures: This study was funded by joint grants from Chang Gung Memorial Hospital-University of Michigan Medical Center to two authors. KC Chung reported receiving funding, research grant, and book royalties from various sources.

Source: Seyferth AV et al. Factors associated with quality care among adults with rheumatoid arthritis. JAMA Netw Open. 2022;5(12):e2246299 (Dec 12). Doi: 10.1001/jamanetworkopen.2022.46299.

Key clinical point: Current use of oral glucocorticoids significantly increased the risk for Staphylococcus aureus bacteremia (SAB) in a dose-dependent manner in patients with rheumatoid arthritis (RA), but the absolute risk was low with biological disease-modifying antirheumatic drug (bDMARD) use.

Major finding: Relative risk for SAB was 2.2-fold (adjusted odds ratio [aOR] 2.2; 95% CI 1.3-4.0) and 9.5-fold (aOR 9.5; 95% CI 3.9-22.7) higher with current use of ≤7.5 and >7.5 mg/day prednisolone-equivalent oral glucocorticoids, respectively. The number needed to harm was approximately 10 times higher with the current use of bDMARD vs >7.5 mg/day oral glucocorticoids (1172 vs 110).

Study details: This nested case-control study included 180 patients with first-time SAB who received glucocorticoids or bDMARD and 720 age- and sex-matched control individuals from a cohort of 30,479 patients with RA.

Disclosures: This study was supported by The Danish Rheumatism Association (TDRA) and Beckett-Fonden. Several authors reported ties with various sources, including TDRA and Beckett-Fonden.

Source: Dieperink SS et al. Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: A nationwide nested case-control study. RMD Open. 2022;8(2):e002636 (Dec 14). Doi: 10.1136/rmdopen-2022-002636

Key clinical point: Current use of oral glucocorticoids significantly increased the risk for Staphylococcus aureus bacteremia (SAB) in a dose-dependent manner in patients with rheumatoid arthritis (RA), but the absolute risk was low with biological disease-modifying antirheumatic drug (bDMARD) use.

Major finding: Relative risk for SAB was 2.2-fold (adjusted odds ratio [aOR] 2.2; 95% CI 1.3-4.0) and 9.5-fold (aOR 9.5; 95% CI 3.9-22.7) higher with current use of ≤7.5 and >7.5 mg/day prednisolone-equivalent oral glucocorticoids, respectively. The number needed to harm was approximately 10 times higher with the current use of bDMARD vs >7.5 mg/day oral glucocorticoids (1172 vs 110).

Study details: This nested case-control study included 180 patients with first-time SAB who received glucocorticoids or bDMARD and 720 age- and sex-matched control individuals from a cohort of 30,479 patients with RA.

Disclosures: This study was supported by The Danish Rheumatism Association (TDRA) and Beckett-Fonden. Several authors reported ties with various sources, including TDRA and Beckett-Fonden.

Source: Dieperink SS et al. Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: A nationwide nested case-control study. RMD Open. 2022;8(2):e002636 (Dec 14). Doi: 10.1136/rmdopen-2022-002636

Key clinical point: Current use of oral glucocorticoids significantly increased the risk for Staphylococcus aureus bacteremia (SAB) in a dose-dependent manner in patients with rheumatoid arthritis (RA), but the absolute risk was low with biological disease-modifying antirheumatic drug (bDMARD) use.

Major finding: Relative risk for SAB was 2.2-fold (adjusted odds ratio [aOR] 2.2; 95% CI 1.3-4.0) and 9.5-fold (aOR 9.5; 95% CI 3.9-22.7) higher with current use of ≤7.5 and >7.5 mg/day prednisolone-equivalent oral glucocorticoids, respectively. The number needed to harm was approximately 10 times higher with the current use of bDMARD vs >7.5 mg/day oral glucocorticoids (1172 vs 110).

Study details: This nested case-control study included 180 patients with first-time SAB who received glucocorticoids or bDMARD and 720 age- and sex-matched control individuals from a cohort of 30,479 patients with RA.

Disclosures: This study was supported by The Danish Rheumatism Association (TDRA) and Beckett-Fonden. Several authors reported ties with various sources, including TDRA and Beckett-Fonden.

Source: Dieperink SS et al. Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: A nationwide nested case-control study. RMD Open. 2022;8(2):e002636 (Dec 14). Doi: 10.1136/rmdopen-2022-002636

Key clinical point: The probability of continued use of glucocorticoids after bridging was low among patients with rheumatoid arthritis (RA), with a shorter oral bridging schedule and lower initial dose being associated with fewer patients taking glucocorticoids at 18 months after bridging.

Major finding: The probability of using or restarting glucocorticoids decreased from 0.18 at 1 month to 0.07 at 6, 12, and 18 months of ending glucocorticoid bridging therapy. A longer duration of bridging schedule (odds ratio [OR] 1.14; 95% CI 1.05-1.24) and higher initial glucocorticoid dose (OR 1.04; 95% CI 1.01-1.06) were associated with more patients taking glucocorticoids at 18 months after bridging.

Study details: This individual patient data meta-analysis of seven clinical trials included 1653 patients with newly diagnosed RA, undifferentiated arthritis, or a high-risk profile for persistent arthritis who received glucocorticoids bridging therapy as initial treatment.

Disclosures: This study did not receive any specific funding. Several authors reported ties with various sources.

Source: van Ouwerkerk L et al. Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Dec 16). Doi: 10.1136/ard-2022-223443

Key clinical point: The probability of continued use of glucocorticoids after bridging was low among patients with rheumatoid arthritis (RA), with a shorter oral bridging schedule and lower initial dose being associated with fewer patients taking glucocorticoids at 18 months after bridging.

Major finding: The probability of using or restarting glucocorticoids decreased from 0.18 at 1 month to 0.07 at 6, 12, and 18 months of ending glucocorticoid bridging therapy. A longer duration of bridging schedule (odds ratio [OR] 1.14; 95% CI 1.05-1.24) and higher initial glucocorticoid dose (OR 1.04; 95% CI 1.01-1.06) were associated with more patients taking glucocorticoids at 18 months after bridging.

Study details: This individual patient data meta-analysis of seven clinical trials included 1653 patients with newly diagnosed RA, undifferentiated arthritis, or a high-risk profile for persistent arthritis who received glucocorticoids bridging therapy as initial treatment.

Disclosures: This study did not receive any specific funding. Several authors reported ties with various sources.

Source: van Ouwerkerk L et al. Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Dec 16). Doi: 10.1136/ard-2022-223443

Key clinical point: The probability of continued use of glucocorticoids after bridging was low among patients with rheumatoid arthritis (RA), with a shorter oral bridging schedule and lower initial dose being associated with fewer patients taking glucocorticoids at 18 months after bridging.

Major finding: The probability of using or restarting glucocorticoids decreased from 0.18 at 1 month to 0.07 at 6, 12, and 18 months of ending glucocorticoid bridging therapy. A longer duration of bridging schedule (odds ratio [OR] 1.14; 95% CI 1.05-1.24) and higher initial glucocorticoid dose (OR 1.04; 95% CI 1.01-1.06) were associated with more patients taking glucocorticoids at 18 months after bridging.

Study details: This individual patient data meta-analysis of seven clinical trials included 1653 patients with newly diagnosed RA, undifferentiated arthritis, or a high-risk profile for persistent arthritis who received glucocorticoids bridging therapy as initial treatment.

Disclosures: This study did not receive any specific funding. Several authors reported ties with various sources.

Source: van Ouwerkerk L et al. Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Dec 16). Doi: 10.1136/ard-2022-223443

Key clinical point: Methotrexate use before conception increased the risk for pregnancy losses and abortion in childbearing-age women with rheumatoid arthritis (RA), with the risk for elective termination of pregnancy (ETOP) being significantly higher with methotrexate use in the period close to conception.

Major finding: Methotrexate use any time before conception was significantly associated with a higher risk for pregnancy losses (adjusted odds ratio [aOR] 2.22; P < .001) and abortion (aOR 1.76; P < .01) in women with vs without RA, with the risk for ETOP being almost 4-fold higher with methotrexate use in the 3-month window before conception (aOR 4.77; P < .05).

Study details: Findings are from a retrospective cohort study including childbearing-age women with RA who did (n = 223) and did not (n = 323) receive methotrexate and those without RA who did not receive methotrexate (n = 1690).

Disclosures: This study was supported by the Italian Society for Rheumatology. This authors did not declare any conflicts of interest.

Source: Zanetti A et al. Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: Retrospective cohort study of the Italian Society for Rheumatology. RMD Open. 2022;8(2):e002412 (Dec 12). Doi: 10.1136/rmdopen-2022-002412

Key clinical point: Methotrexate use before conception increased the risk for pregnancy losses and abortion in childbearing-age women with rheumatoid arthritis (RA), with the risk for elective termination of pregnancy (ETOP) being significantly higher with methotrexate use in the period close to conception.

Major finding: Methotrexate use any time before conception was significantly associated with a higher risk for pregnancy losses (adjusted odds ratio [aOR] 2.22; P < .001) and abortion (aOR 1.76; P < .01) in women with vs without RA, with the risk for ETOP being almost 4-fold higher with methotrexate use in the 3-month window before conception (aOR 4.77; P < .05).

Study details: Findings are from a retrospective cohort study including childbearing-age women with RA who did (n = 223) and did not (n = 323) receive methotrexate and those without RA who did not receive methotrexate (n = 1690).

Disclosures: This study was supported by the Italian Society for Rheumatology. This authors did not declare any conflicts of interest.

Source: Zanetti A et al. Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: Retrospective cohort study of the Italian Society for Rheumatology. RMD Open. 2022;8(2):e002412 (Dec 12). Doi: 10.1136/rmdopen-2022-002412

Key clinical point: Methotrexate use before conception increased the risk for pregnancy losses and abortion in childbearing-age women with rheumatoid arthritis (RA), with the risk for elective termination of pregnancy (ETOP) being significantly higher with methotrexate use in the period close to conception.

Major finding: Methotrexate use any time before conception was significantly associated with a higher risk for pregnancy losses (adjusted odds ratio [aOR] 2.22; P < .001) and abortion (aOR 1.76; P < .01) in women with vs without RA, with the risk for ETOP being almost 4-fold higher with methotrexate use in the 3-month window before conception (aOR 4.77; P < .05).

Study details: Findings are from a retrospective cohort study including childbearing-age women with RA who did (n = 223) and did not (n = 323) receive methotrexate and those without RA who did not receive methotrexate (n = 1690).

Disclosures: This study was supported by the Italian Society for Rheumatology. This authors did not declare any conflicts of interest.

Source: Zanetti A et al. Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: Retrospective cohort study of the Italian Society for Rheumatology. RMD Open. 2022;8(2):e002412 (Dec 12). Doi: 10.1136/rmdopen-2022-002412

Clinical cardiologist Heba Wassif, MD, MPH, knows the value of working with her fellow rheumatologists, surgeons, and other clinicians to establish a care plan for her patients with cardiac conditions and autoimmune diseases.

She is the cofounder of the Cleveland Clinic’s new cardio-rheumatology program, which places an emphasis on multidisciplinary care. In her role, Dr. Wassif closely follows her patients, and if she sees any inflammation or any other condition that requires the rheumatologist, she reaches out to her colleagues to adjust medications if needed.

Collaboration with a rheumatologist was important when a patient with valvular disease was prepping for surgery. The patient was on significant immunosuppressants and the surgery had to be timed appropriately, accounting for any decreases in her immunosuppression, explained Dr. Wassif, director of inpatient clinical cardiology at Cleveland Clinic in Ohio.

Cardio-rheumatology programs are “the newest child” in a series of cardiology offshoots focusing on different populations. Cardio-oncology and cardio-obstetrics took off about 6 years ago, with cardio-rheumatology clinics and interested physicians rising in number over the last several years, Dr. Wassif noted.

The relationship between cardiovascular diseases and rheumatologic conditions is certainly recognized more often, “which means more literature is being published to discuss the link,” according to Rekha Mankad, MD, a trailblazer of this model of care. She directs the Women’s Heart Clinic at Mayo Clinic in Rochester, Minn., which was one of the earliest adopters of a cardio-rheumatology clinic.

Challenges of treating cardiac, rheumatologic conditions

The rise in clinics addresses the longstanding connection between autoimmune disorders and cardiac conditions.

Cardiologists have known that there is an element of inflammation that contributes to atherosclerosis, said Dr. Wassif, who has researched this topic extensively. A recent study she led found a strong association between rheumatic immune-mediated inflammatory diseases (IMIDs) and high risk of acute coronary syndrome in Medicare patients.

“This particular population has a very clear increased risk for cardiovascular conditions, including valve disease and heart failure,” she emphasized.

Patients with rheumatoid arthritis and lupus have up to a twofold and eightfold higher risk of heart disease, respectively, noted Michael S. Garshick, MD, a cardiovascular disease specialist who directs the cardio-rheumatology program at NYU-Langone Health, in New York. Cardiologists “have really developed an understanding that the immune system can impact the heart, and that there’s a need for people to understand the nuance behind how the immune system can affect them and what to do about it,” Dr. Garshick said.

Courtesy Rob Lisak

‘Reading the tea leaves’

Each program has its own unique story. For the Cleveland Clinic, the concept of a cardio-rheumatology program began during the COVID-19 pandemic in 2020. Developing such a concept and gaining institutional acceptance is always a work in process, Dr. Wassif said. “It’s not that you decide one day that you’re going to build a center, and that center is going to come into fruition overnight. You first gauge interest within your division. Who are the individuals that are interested in this area?”

Cleveland Clinic’s center is seeking to build relations between medical disciplines while spotlighting the concept of cardio-rheumatology, said Dr. Wassif, who has been providing education within the clinic and at other health institutions to ensure that patients receive appropriate attention early.

NYU-Langone launched its program amid this heightened awareness that the immune system could affect atherosclerosis, “kind of reading of the tea leaves, so to speak,” Dr. Garshick said.

Several clinical trials served as a catalyst for this movement. “A lot of clinical cardiologists were never 100% convinced that targeting the immune system reduced cardiovascular disease,” he said. Then the CANTOS clinical trial came along and showed for the first time that a therapeutic monoclonal antibody targeting interleukin-1beta, a cytokine central to inflammatory response, could in fact reduce cardiovascular disease.

Trials like this, along with epidemiologic literature connecting the rheumatologic and the autoimmune conditions with cardiovascular disease, pushed this concept to the forefront, Dr. Garshick said.

The notion that a clinic could successfully address cardiac problems in patients with rheumatic diseases yielded promising returns at Women’s College Hospital in Toronto, according to a report presented at the 2018 American College of Rheumatology annual meeting. Researchers reported that patients with rheumatologic conditions who attended a cardio-rheumatology clinic at this center saw improvements in care. The clinic identified increased cardiovascular risk and early atherosclerosis, and 53.8% of patients altered their medications after being seen in the clinic.

A total of 39.7% and 32.1% received lipid lowering and antiplatelet therapies, respectively, and 14% received antihypertensive therapy. A small percentage were treated for heart failure or placed on lifelong anticoagulation therapy for atrial fibrillation, and one patient received a percutaneous coronary stent.
 

Ins and outs of the referral process

Initially designed for preventive cardiac risk assessment, Yale’s program evolved into a multidisciplinary, patient-centered approach for the management of complex cardiovascular conditions in patients with autoimmune rheumatologic diseases.

The program is open to anyone who carries a diagnosis of rheumatologic disease or has elevated inflammatory markers. “Every patient, regardless of the reason for the referral, receives a cardiovascular risk assessment,” Dr. Furman said.

Harold Shapiro

A personalized assessment to reduce cardiac risk

NYU-Langone’s program offers opportunities to educate patients about the link between cardiac and rheumatologic disease.

“Their rheumatologist or their dermatologist will say, ‘Hey, have you heard about the connection between psoriasis, psoriatic or rheumatoid arthritis, and heart disease and the risk of heart attack or stroke?’ ” Dr. Garshick said.

The patients will often say they know nothing about these connections and want to learn more about how to treat it.

“We’ll say, ‘we have someone here that can help you.’ They’ll send them to myself or other colleagues like me across the country. We’ll assess blood pressure, weight, lipids, hemoglobin A1c, and other serologic and oftentimes imaging biomarkers of cardiovascular risk.” The patients will receive a personalized assessment, listing things they can do to lower their risk, whether it’s diet, exercise, or lifestyle. “Many times it can involve medications to reduce heart disease risk,” said Dr. Garshick.

In some instances, a rheumatologist or dermatologist may be concerned about starting a patient on a specific medication for the disease such as a JAK inhibitor. “We’ll help assess their risk because there’s been a lot of literature out in the rheumatology world about the risk of JAK inhibitors and heart disease and blood clots,” said Dr. Garshick.

Dr. Garshick also sees patients with rheumatologic conditions who have a specific cardiovascular concern or complaint such as shortness of breath or chest pain. “We’ll work that up with a specific knowledge of the underlying immune condition and how that may impact their heart,” he said.
 

Advances in research

As they continue to see patients and devise specific care plans, developers of cardio-rheumatology programs have been supplementing their work with ongoing research.

Yale’s clinic is expanding this year to include a new attending physician, Attila Feher, MD, PhD, who has conducted research in autoimmunity and microcirculation using molecular imaging and multimodality imaging techniques. Prevalence of coronary microvascular dysfunction appears to be increased in this patient population, Dr. Furman said.

Dr. Wassif recently coauthored a paper that examined patients with underlying rheumatologic conditions who undergo valvular and aortic valve replacement. “To our surprise, there was really no difference between patients with autoimmune conditions and others with nonautoimmune conditions,” she said, adding that the study had its limitations.

Other work includes data on Medicare patients with ST- and non-ST-elevation myocardial infarctions who have an underlying autoimmune disorder. Dr. Wassif and her colleagues found that their long-term outcomes are worse than those of patients without these conditions. “It’s unclear if worse outcomes are related to complications of autoimmunity versus the extent of their underlying disease. This is a work in progress and certainly an area that is ripe for research.”

Dr. Garshick and other collaborators at NYU have been focusing on the endothelium, specifically platelet biology in patients with psoriasis, psoriatic arthritis, and lupus. “We’re about to start the same research with gout as well,” he said.

“The process we’re most interested in is understanding how these diseases impact the early stages of cholesterol. And the way we’re doing that is evaluating the vasculature, specifically the endothelium,” he said.

He has finished two clinical trials that evaluate how standard heart disease medications such as aspirin and statins impact or can potentially benefit patients with psoriasis and/or psoriatic arthritis. “We have a whole list of other trials in the pipeline with other institutions across the country.”

Through a grant, Dr. Mankad is assessing whether a PET scan could detect inflammation in the hearts of rheumatoid arthritis patients. “We’re looking to see if the reason these patients have heart failure later in life is because their heart muscle actually shows evidence of inflammation, even when they have no symptoms,” she explained.

Other tests such as echocardiogram and CT scans will be used to evaluate coronary disease in about 40-50 patients. The goal of using these multiple imaging tools is to find markers indicating that the heart is affected by rheumatoid arthritis, which may indicate a higher likelihood of developing heart failure, she said.
 

Clinics are popping up

Through these new clinics, some collaborations have emerged. Dr. Garshick works closely with Brigham and Women’s Hospital, which has a similar cardio-rheumatology program, run by Brittany Weber, MD, to exchange ideas, discuss challenging cases, and collaborate.

“There are a lot of clinics like us popping up across the country,” he observed. Every so often, he hears from other institutions that are interested in starting their own cardio-rheumatology programs. “They ask us: How do you start, what should we look for?”

It’s an education process for both patients and providers, Dr. Garshick emphasized. “I also think it’s a bandwidth issue. Many of our rheumatology and dermatology colleagues are acutely aware of the connection, but there may not be enough time at a clinic visit to really go in depth” with these dual conditions, he said.

NYU-Langone Health for the past several years has been holding a symposium to educate people on the cardio-rheumatology connection and treating inflammation in cardiovascular disease. This year’s symposium, held in conjunction with Brigham and Women’s Hospital, is scheduled for April 28. For more information, visit the course website: nyulmc.org/cvinflammationcme.

“What we’re trying to do is help [other institutions] get that bandwidth” to adequately help and serve these patients, he said.

Dr. Garshick has received consultant fees from Abbvie and Horizon therapeutics and an unrestricted research grant from Pfizer. No other sources had relevant financial disclosures.

Clinical cardiologist Heba Wassif, MD, MPH, knows the value of working with her fellow rheumatologists, surgeons, and other clinicians to establish a care plan for her patients with cardiac conditions and autoimmune diseases.

She is the cofounder of the Cleveland Clinic’s new cardio-rheumatology program, which places an emphasis on multidisciplinary care. In her role, Dr. Wassif closely follows her patients, and if she sees any inflammation or any other condition that requires the rheumatologist, she reaches out to her colleagues to adjust medications if needed.

Collaboration with a rheumatologist was important when a patient with valvular disease was prepping for surgery. The patient was on significant immunosuppressants and the surgery had to be timed appropriately, accounting for any decreases in her immunosuppression, explained Dr. Wassif, director of inpatient clinical cardiology at Cleveland Clinic in Ohio.

Cardio-rheumatology programs are “the newest child” in a series of cardiology offshoots focusing on different populations. Cardio-oncology and cardio-obstetrics took off about 6 years ago, with cardio-rheumatology clinics and interested physicians rising in number over the last several years, Dr. Wassif noted.

The relationship between cardiovascular diseases and rheumatologic conditions is certainly recognized more often, “which means more literature is being published to discuss the link,” according to Rekha Mankad, MD, a trailblazer of this model of care. She directs the Women’s Heart Clinic at Mayo Clinic in Rochester, Minn., which was one of the earliest adopters of a cardio-rheumatology clinic.

Challenges of treating cardiac, rheumatologic conditions

The rise in clinics addresses the longstanding connection between autoimmune disorders and cardiac conditions.

Cardiologists have known that there is an element of inflammation that contributes to atherosclerosis, said Dr. Wassif, who has researched this topic extensively. A recent study she led found a strong association between rheumatic immune-mediated inflammatory diseases (IMIDs) and high risk of acute coronary syndrome in Medicare patients.

“This particular population has a very clear increased risk for cardiovascular conditions, including valve disease and heart failure,” she emphasized.

Patients with rheumatoid arthritis and lupus have up to a twofold and eightfold higher risk of heart disease, respectively, noted Michael S. Garshick, MD, a cardiovascular disease specialist who directs the cardio-rheumatology program at NYU-Langone Health, in New York. Cardiologists “have really developed an understanding that the immune system can impact the heart, and that there’s a need for people to understand the nuance behind how the immune system can affect them and what to do about it,” Dr. Garshick said.

Courtesy Rob Lisak

‘Reading the tea leaves’

Each program has its own unique story. For the Cleveland Clinic, the concept of a cardio-rheumatology program began during the COVID-19 pandemic in 2020. Developing such a concept and gaining institutional acceptance is always a work in process, Dr. Wassif said. “It’s not that you decide one day that you’re going to build a center, and that center is going to come into fruition overnight. You first gauge interest within your division. Who are the individuals that are interested in this area?”

Cleveland Clinic’s center is seeking to build relations between medical disciplines while spotlighting the concept of cardio-rheumatology, said Dr. Wassif, who has been providing education within the clinic and at other health institutions to ensure that patients receive appropriate attention early.

NYU-Langone launched its program amid this heightened awareness that the immune system could affect atherosclerosis, “kind of reading of the tea leaves, so to speak,” Dr. Garshick said.

Several clinical trials served as a catalyst for this movement. “A lot of clinical cardiologists were never 100% convinced that targeting the immune system reduced cardiovascular disease,” he said. Then the CANTOS clinical trial came along and showed for the first time that a therapeutic monoclonal antibody targeting interleukin-1beta, a cytokine central to inflammatory response, could in fact reduce cardiovascular disease.

Trials like this, along with epidemiologic literature connecting the rheumatologic and the autoimmune conditions with cardiovascular disease, pushed this concept to the forefront, Dr. Garshick said.

The notion that a clinic could successfully address cardiac problems in patients with rheumatic diseases yielded promising returns at Women’s College Hospital in Toronto, according to a report presented at the 2018 American College of Rheumatology annual meeting. Researchers reported that patients with rheumatologic conditions who attended a cardio-rheumatology clinic at this center saw improvements in care. The clinic identified increased cardiovascular risk and early atherosclerosis, and 53.8% of patients altered their medications after being seen in the clinic.

A total of 39.7% and 32.1% received lipid lowering and antiplatelet therapies, respectively, and 14% received antihypertensive therapy. A small percentage were treated for heart failure or placed on lifelong anticoagulation therapy for atrial fibrillation, and one patient received a percutaneous coronary stent.
 

Ins and outs of the referral process

Initially designed for preventive cardiac risk assessment, Yale’s program evolved into a multidisciplinary, patient-centered approach for the management of complex cardiovascular conditions in patients with autoimmune rheumatologic diseases.

The program is open to anyone who carries a diagnosis of rheumatologic disease or has elevated inflammatory markers. “Every patient, regardless of the reason for the referral, receives a cardiovascular risk assessment,” Dr. Furman said.

Harold Shapiro

A personalized assessment to reduce cardiac risk

NYU-Langone’s program offers opportunities to educate patients about the link between cardiac and rheumatologic disease.

“Their rheumatologist or their dermatologist will say, ‘Hey, have you heard about the connection between psoriasis, psoriatic or rheumatoid arthritis, and heart disease and the risk of heart attack or stroke?’ ” Dr. Garshick said.

The patients will often say they know nothing about these connections and want to learn more about how to treat it.

“We’ll say, ‘we have someone here that can help you.’ They’ll send them to myself or other colleagues like me across the country. We’ll assess blood pressure, weight, lipids, hemoglobin A1c, and other serologic and oftentimes imaging biomarkers of cardiovascular risk.” The patients will receive a personalized assessment, listing things they can do to lower their risk, whether it’s diet, exercise, or lifestyle. “Many times it can involve medications to reduce heart disease risk,” said Dr. Garshick.

In some instances, a rheumatologist or dermatologist may be concerned about starting a patient on a specific medication for the disease such as a JAK inhibitor. “We’ll help assess their risk because there’s been a lot of literature out in the rheumatology world about the risk of JAK inhibitors and heart disease and blood clots,” said Dr. Garshick.

Dr. Garshick also sees patients with rheumatologic conditions who have a specific cardiovascular concern or complaint such as shortness of breath or chest pain. “We’ll work that up with a specific knowledge of the underlying immune condition and how that may impact their heart,” he said.
 

Advances in research

As they continue to see patients and devise specific care plans, developers of cardio-rheumatology programs have been supplementing their work with ongoing research.

Yale’s clinic is expanding this year to include a new attending physician, Attila Feher, MD, PhD, who has conducted research in autoimmunity and microcirculation using molecular imaging and multimodality imaging techniques. Prevalence of coronary microvascular dysfunction appears to be increased in this patient population, Dr. Furman said.

Dr. Wassif recently coauthored a paper that examined patients with underlying rheumatologic conditions who undergo valvular and aortic valve replacement. “To our surprise, there was really no difference between patients with autoimmune conditions and others with nonautoimmune conditions,” she said, adding that the study had its limitations.

Other work includes data on Medicare patients with ST- and non-ST-elevation myocardial infarctions who have an underlying autoimmune disorder. Dr. Wassif and her colleagues found that their long-term outcomes are worse than those of patients without these conditions. “It’s unclear if worse outcomes are related to complications of autoimmunity versus the extent of their underlying disease. This is a work in progress and certainly an area that is ripe for research.”

Dr. Garshick and other collaborators at NYU have been focusing on the endothelium, specifically platelet biology in patients with psoriasis, psoriatic arthritis, and lupus. “We’re about to start the same research with gout as well,” he said.

“The process we’re most interested in is understanding how these diseases impact the early stages of cholesterol. And the way we’re doing that is evaluating the vasculature, specifically the endothelium,” he said.

He has finished two clinical trials that evaluate how standard heart disease medications such as aspirin and statins impact or can potentially benefit patients with psoriasis and/or psoriatic arthritis. “We have a whole list of other trials in the pipeline with other institutions across the country.”

Through a grant, Dr. Mankad is assessing whether a PET scan could detect inflammation in the hearts of rheumatoid arthritis patients. “We’re looking to see if the reason these patients have heart failure later in life is because their heart muscle actually shows evidence of inflammation, even when they have no symptoms,” she explained.

Other tests such as echocardiogram and CT scans will be used to evaluate coronary disease in about 40-50 patients. The goal of using these multiple imaging tools is to find markers indicating that the heart is affected by rheumatoid arthritis, which may indicate a higher likelihood of developing heart failure, she said.
 

Clinics are popping up

Through these new clinics, some collaborations have emerged. Dr. Garshick works closely with Brigham and Women’s Hospital, which has a similar cardio-rheumatology program, run by Brittany Weber, MD, to exchange ideas, discuss challenging cases, and collaborate.

“There are a lot of clinics like us popping up across the country,” he observed. Every so often, he hears from other institutions that are interested in starting their own cardio-rheumatology programs. “They ask us: How do you start, what should we look for?”

It’s an education process for both patients and providers, Dr. Garshick emphasized. “I also think it’s a bandwidth issue. Many of our rheumatology and dermatology colleagues are acutely aware of the connection, but there may not be enough time at a clinic visit to really go in depth” with these dual conditions, he said.

NYU-Langone Health for the past several years has been holding a symposium to educate people on the cardio-rheumatology connection and treating inflammation in cardiovascular disease. This year’s symposium, held in conjunction with Brigham and Women’s Hospital, is scheduled for April 28. For more information, visit the course website: nyulmc.org/cvinflammationcme.

“What we’re trying to do is help [other institutions] get that bandwidth” to adequately help and serve these patients, he said.

Dr. Garshick has received consultant fees from Abbvie and Horizon therapeutics and an unrestricted research grant from Pfizer. No other sources had relevant financial disclosures.

Clinical cardiologist Heba Wassif, MD, MPH, knows the value of working with her fellow rheumatologists, surgeons, and other clinicians to establish a care plan for her patients with cardiac conditions and autoimmune diseases.

She is the cofounder of the Cleveland Clinic’s new cardio-rheumatology program, which places an emphasis on multidisciplinary care. In her role, Dr. Wassif closely follows her patients, and if she sees any inflammation or any other condition that requires the rheumatologist, she reaches out to her colleagues to adjust medications if needed.

Collaboration with a rheumatologist was important when a patient with valvular disease was prepping for surgery. The patient was on significant immunosuppressants and the surgery had to be timed appropriately, accounting for any decreases in her immunosuppression, explained Dr. Wassif, director of inpatient clinical cardiology at Cleveland Clinic in Ohio.

Cardio-rheumatology programs are “the newest child” in a series of cardiology offshoots focusing on different populations. Cardio-oncology and cardio-obstetrics took off about 6 years ago, with cardio-rheumatology clinics and interested physicians rising in number over the last several years, Dr. Wassif noted.

The relationship between cardiovascular diseases and rheumatologic conditions is certainly recognized more often, “which means more literature is being published to discuss the link,” according to Rekha Mankad, MD, a trailblazer of this model of care. She directs the Women’s Heart Clinic at Mayo Clinic in Rochester, Minn., which was one of the earliest adopters of a cardio-rheumatology clinic.

Challenges of treating cardiac, rheumatologic conditions

The rise in clinics addresses the longstanding connection between autoimmune disorders and cardiac conditions.

Cardiologists have known that there is an element of inflammation that contributes to atherosclerosis, said Dr. Wassif, who has researched this topic extensively. A recent study she led found a strong association between rheumatic immune-mediated inflammatory diseases (IMIDs) and high risk of acute coronary syndrome in Medicare patients.

“This particular population has a very clear increased risk for cardiovascular conditions, including valve disease and heart failure,” she emphasized.

Patients with rheumatoid arthritis and lupus have up to a twofold and eightfold higher risk of heart disease, respectively, noted Michael S. Garshick, MD, a cardiovascular disease specialist who directs the cardio-rheumatology program at NYU-Langone Health, in New York. Cardiologists “have really developed an understanding that the immune system can impact the heart, and that there’s a need for people to understand the nuance behind how the immune system can affect them and what to do about it,” Dr. Garshick said.

Courtesy Rob Lisak

‘Reading the tea leaves’

Each program has its own unique story. For the Cleveland Clinic, the concept of a cardio-rheumatology program began during the COVID-19 pandemic in 2020. Developing such a concept and gaining institutional acceptance is always a work in process, Dr. Wassif said. “It’s not that you decide one day that you’re going to build a center, and that center is going to come into fruition overnight. You first gauge interest within your division. Who are the individuals that are interested in this area?”

Cleveland Clinic’s center is seeking to build relations between medical disciplines while spotlighting the concept of cardio-rheumatology, said Dr. Wassif, who has been providing education within the clinic and at other health institutions to ensure that patients receive appropriate attention early.

NYU-Langone launched its program amid this heightened awareness that the immune system could affect atherosclerosis, “kind of reading of the tea leaves, so to speak,” Dr. Garshick said.

Several clinical trials served as a catalyst for this movement. “A lot of clinical cardiologists were never 100% convinced that targeting the immune system reduced cardiovascular disease,” he said. Then the CANTOS clinical trial came along and showed for the first time that a therapeutic monoclonal antibody targeting interleukin-1beta, a cytokine central to inflammatory response, could in fact reduce cardiovascular disease.

Trials like this, along with epidemiologic literature connecting the rheumatologic and the autoimmune conditions with cardiovascular disease, pushed this concept to the forefront, Dr. Garshick said.

The notion that a clinic could successfully address cardiac problems in patients with rheumatic diseases yielded promising returns at Women’s College Hospital in Toronto, according to a report presented at the 2018 American College of Rheumatology annual meeting. Researchers reported that patients with rheumatologic conditions who attended a cardio-rheumatology clinic at this center saw improvements in care. The clinic identified increased cardiovascular risk and early atherosclerosis, and 53.8% of patients altered their medications after being seen in the clinic.

A total of 39.7% and 32.1% received lipid lowering and antiplatelet therapies, respectively, and 14% received antihypertensive therapy. A small percentage were treated for heart failure or placed on lifelong anticoagulation therapy for atrial fibrillation, and one patient received a percutaneous coronary stent.
 

Ins and outs of the referral process

Initially designed for preventive cardiac risk assessment, Yale’s program evolved into a multidisciplinary, patient-centered approach for the management of complex cardiovascular conditions in patients with autoimmune rheumatologic diseases.

The program is open to anyone who carries a diagnosis of rheumatologic disease or has elevated inflammatory markers. “Every patient, regardless of the reason for the referral, receives a cardiovascular risk assessment,” Dr. Furman said.

Harold Shapiro

A personalized assessment to reduce cardiac risk

NYU-Langone’s program offers opportunities to educate patients about the link between cardiac and rheumatologic disease.

“Their rheumatologist or their dermatologist will say, ‘Hey, have you heard about the connection between psoriasis, psoriatic or rheumatoid arthritis, and heart disease and the risk of heart attack or stroke?’ ” Dr. Garshick said.

The patients will often say they know nothing about these connections and want to learn more about how to treat it.

“We’ll say, ‘we have someone here that can help you.’ They’ll send them to myself or other colleagues like me across the country. We’ll assess blood pressure, weight, lipids, hemoglobin A1c, and other serologic and oftentimes imaging biomarkers of cardiovascular risk.” The patients will receive a personalized assessment, listing things they can do to lower their risk, whether it’s diet, exercise, or lifestyle. “Many times it can involve medications to reduce heart disease risk,” said Dr. Garshick.

In some instances, a rheumatologist or dermatologist may be concerned about starting a patient on a specific medication for the disease such as a JAK inhibitor. “We’ll help assess their risk because there’s been a lot of literature out in the rheumatology world about the risk of JAK inhibitors and heart disease and blood clots,” said Dr. Garshick.

Dr. Garshick also sees patients with rheumatologic conditions who have a specific cardiovascular concern or complaint such as shortness of breath or chest pain. “We’ll work that up with a specific knowledge of the underlying immune condition and how that may impact their heart,” he said.
 

Advances in research

As they continue to see patients and devise specific care plans, developers of cardio-rheumatology programs have been supplementing their work with ongoing research.

Yale’s clinic is expanding this year to include a new attending physician, Attila Feher, MD, PhD, who has conducted research in autoimmunity and microcirculation using molecular imaging and multimodality imaging techniques. Prevalence of coronary microvascular dysfunction appears to be increased in this patient population, Dr. Furman said.

Dr. Wassif recently coauthored a paper that examined patients with underlying rheumatologic conditions who undergo valvular and aortic valve replacement. “To our surprise, there was really no difference between patients with autoimmune conditions and others with nonautoimmune conditions,” she said, adding that the study had its limitations.

Other work includes data on Medicare patients with ST- and non-ST-elevation myocardial infarctions who have an underlying autoimmune disorder. Dr. Wassif and her colleagues found that their long-term outcomes are worse than those of patients without these conditions. “It’s unclear if worse outcomes are related to complications of autoimmunity versus the extent of their underlying disease. This is a work in progress and certainly an area that is ripe for research.”

Dr. Garshick and other collaborators at NYU have been focusing on the endothelium, specifically platelet biology in patients with psoriasis, psoriatic arthritis, and lupus. “We’re about to start the same research with gout as well,” he said.

“The process we’re most interested in is understanding how these diseases impact the early stages of cholesterol. And the way we’re doing that is evaluating the vasculature, specifically the endothelium,” he said.

He has finished two clinical trials that evaluate how standard heart disease medications such as aspirin and statins impact or can potentially benefit patients with psoriasis and/or psoriatic arthritis. “We have a whole list of other trials in the pipeline with other institutions across the country.”

Through a grant, Dr. Mankad is assessing whether a PET scan could detect inflammation in the hearts of rheumatoid arthritis patients. “We’re looking to see if the reason these patients have heart failure later in life is because their heart muscle actually shows evidence of inflammation, even when they have no symptoms,” she explained.

Other tests such as echocardiogram and CT scans will be used to evaluate coronary disease in about 40-50 patients. The goal of using these multiple imaging tools is to find markers indicating that the heart is affected by rheumatoid arthritis, which may indicate a higher likelihood of developing heart failure, she said.
 

Clinics are popping up

Through these new clinics, some collaborations have emerged. Dr. Garshick works closely with Brigham and Women’s Hospital, which has a similar cardio-rheumatology program, run by Brittany Weber, MD, to exchange ideas, discuss challenging cases, and collaborate.

“There are a lot of clinics like us popping up across the country,” he observed. Every so often, he hears from other institutions that are interested in starting their own cardio-rheumatology programs. “They ask us: How do you start, what should we look for?”

It’s an education process for both patients and providers, Dr. Garshick emphasized. “I also think it’s a bandwidth issue. Many of our rheumatology and dermatology colleagues are acutely aware of the connection, but there may not be enough time at a clinic visit to really go in depth” with these dual conditions, he said.

NYU-Langone Health for the past several years has been holding a symposium to educate people on the cardio-rheumatology connection and treating inflammation in cardiovascular disease. This year’s symposium, held in conjunction with Brigham and Women’s Hospital, is scheduled for April 28. For more information, visit the course website: nyulmc.org/cvinflammationcme.

“What we’re trying to do is help [other institutions] get that bandwidth” to adequately help and serve these patients, he said.

Dr. Garshick has received consultant fees from Abbvie and Horizon therapeutics and an unrestricted research grant from Pfizer. No other sources had relevant financial disclosures.

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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