Improved efficacy with subcutaneous vs intravenous infliximab in RA

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Key clinical point: Subcutaneous vs intravenous infliximab demonstrated improved efficacy in patients with rheumatoid arthritis (RA) who were inadequate responders to methotrexate (methotrexate-IR).

 

Major finding: At week 30, subcutaneous vs intravenous infliximab led to significantly lower Disease Activity Scores in 28 joints-C-reactive protein (DAS28-CRP; mean 3.07 vs 3.58; P  =  .0001) and significantly higher proportion of patients achieving DAS28-CRP low disease activity and remission (53.3% vs 38.5%; P  =  .0062), with no significant between-group difference after the switch to subcutaneous infliximab.

 

Study details: This post hoc analysis of a phase 3 trial included 339 patients with active RA who were methotrexate-IR and were randomly assigned to receive subcutaneous or intravenous infliximab; patients assigned to receive intravenous infliximab switched to subcutaneous infliximab from week 30 to 54.

 

Disclosures: This study was supported by Celltrion Healthcare Co., Ltd. Five authors declared being full-time employees of or receiving personal fees for advisory board and speaker’s bureau and research grants from Celltrion outside this work. Several authors reported ties with other various sources.

 

Source: Constantin A et al. Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: A post-hoc analysis of a randomised phase III trial. Rheumatology (Oxford). 2022 (Dec 19). Doi: 10.1093/rheumatology/keac689

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Key clinical point: Subcutaneous vs intravenous infliximab demonstrated improved efficacy in patients with rheumatoid arthritis (RA) who were inadequate responders to methotrexate (methotrexate-IR).

 

Major finding: At week 30, subcutaneous vs intravenous infliximab led to significantly lower Disease Activity Scores in 28 joints-C-reactive protein (DAS28-CRP; mean 3.07 vs 3.58; P  =  .0001) and significantly higher proportion of patients achieving DAS28-CRP low disease activity and remission (53.3% vs 38.5%; P  =  .0062), with no significant between-group difference after the switch to subcutaneous infliximab.

 

Study details: This post hoc analysis of a phase 3 trial included 339 patients with active RA who were methotrexate-IR and were randomly assigned to receive subcutaneous or intravenous infliximab; patients assigned to receive intravenous infliximab switched to subcutaneous infliximab from week 30 to 54.

 

Disclosures: This study was supported by Celltrion Healthcare Co., Ltd. Five authors declared being full-time employees of or receiving personal fees for advisory board and speaker’s bureau and research grants from Celltrion outside this work. Several authors reported ties with other various sources.

 

Source: Constantin A et al. Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: A post-hoc analysis of a randomised phase III trial. Rheumatology (Oxford). 2022 (Dec 19). Doi: 10.1093/rheumatology/keac689

Key clinical point: Subcutaneous vs intravenous infliximab demonstrated improved efficacy in patients with rheumatoid arthritis (RA) who were inadequate responders to methotrexate (methotrexate-IR).

 

Major finding: At week 30, subcutaneous vs intravenous infliximab led to significantly lower Disease Activity Scores in 28 joints-C-reactive protein (DAS28-CRP; mean 3.07 vs 3.58; P  =  .0001) and significantly higher proportion of patients achieving DAS28-CRP low disease activity and remission (53.3% vs 38.5%; P  =  .0062), with no significant between-group difference after the switch to subcutaneous infliximab.

 

Study details: This post hoc analysis of a phase 3 trial included 339 patients with active RA who were methotrexate-IR and were randomly assigned to receive subcutaneous or intravenous infliximab; patients assigned to receive intravenous infliximab switched to subcutaneous infliximab from week 30 to 54.

 

Disclosures: This study was supported by Celltrion Healthcare Co., Ltd. Five authors declared being full-time employees of or receiving personal fees for advisory board and speaker’s bureau and research grants from Celltrion outside this work. Several authors reported ties with other various sources.

 

Source: Constantin A et al. Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: A post-hoc analysis of a randomised phase III trial. Rheumatology (Oxford). 2022 (Dec 19). Doi: 10.1093/rheumatology/keac689

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TNFi raises the risk for septic arthritis in seropositive RA

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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

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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

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Frequent joint inflammation increases local joint damage progression in early RA

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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

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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

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Multidisciplinary lifestyle program improves outcomes in RA

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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

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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

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Tapering glucocorticoids to ≤2.5 mg/day increases the risk for flare in patients receiving bDMARD in RA

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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

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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

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Comorbidity burden tied to lower likelihood of achieving quality care in RA

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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.

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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.

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Oral glucocorticoid use raises risk for Staphylococcus aureus bacteremia in RA

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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

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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

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Most patients successfully discontinue glucocorticoids after initiation as bridging therapy in RA

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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

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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

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Methotrexate use needs close monitoring in patients with RA of childbearing age

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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

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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

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Ospemifene and HT boost vaginal microbiome in vulvovaginal atrophy

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The selective estrogen receptor modulator ospemifene appears to improve the vaginal microbiome of postmenopausal women with vulvovaginal atrophy (VVA), according to results from a small Italian case-control study in the journal Menopause.

Dr. Cristina M. Meriggiola

The study sheds microbiological light on the mechanisms of ospemifene and low-dose systemic hormone therapy, which are widely used to treat genitourinary symptoms. Both had a positive effect on vaginal well-being, likely by reducing potentially harmful bacteria and increasing health-promoting acid-friendly microorganisms, writes a group led by M. Cristina Meriggiola, MD, PhD, of the gynecology and physiopathology of human reproduction unit at the University of Bologna, Italy.

Dr. Stephanie S. Faubion

VVA occurs in about 50% of postmenopausal women and produces a less favorable, less acidic vaginal microbiome profile than that of unaffected women. “The loss of estrogen leads to lower concentrations of Lactobacilli, bacteria that lower the pH. As a result, other bacterial species fill in the void,” explained Stephanie S. Faubion, MD, MBA, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Fla., and medical director of the North American Menopause Society.

Tina Murphy

Added Tina Murphy, APN, a NAMS-certified menopause practitioner at Northwestern Medicine Orland Park in Illinois, “When this protective flora declines, then pathogenic bacteria can predominate the microbiome, which can contribute to vaginal irritation, infection, UTI’s, dyspareunia, and discomfort. Balancing and restoring the microbiome can mitigate the effects of estrogen depletion on the vaginal tissue and prevent the untoward effects of the hypoestrogenic state.” While ospemifene and hormone therapy are common therapies for the genitourinary symptoms of menopause, the focus has been on their treatment efficacy, not their effect on the microbiome profile, added Dr. Faubion. Only about 9% of women with menopause-related genitourinary symptoms receive prescription treatment, she added.
 

The study

Of 67 eligible postmenopausal participants in their mid-50s enrolled at a gynecology clinic from April 2019 to February 2020, 39 were diagnosed with VVA and 28 were considered healthy controls. In the atrophic group, 20 were prescribed ospemifene and 19 received hormone treatment.

Only those women with VVA but no menopausal vasomotor symptoms received ospemifene (60 mg/day); symptomatic women received hormone therapy according to guidelines.

The researchers calculated the women’s vaginal health index (VHI) based on elasticity, secretions, pH level, epithelial mucosa, and hydration. They used swabs to assess vaginal maturation index (VMI) by percentages of superficial, intermediate, and parabasal cells. Evaluation of the vaginal microbiome was done with 16S rRNA gene sequencing, and clinical and microbiological analyses were repeated after 3 months.

The vaginal microbiome of atrophic women was characterized by a significant reduction of benign Lactobacillus bacteria (P = .002) and an increase of potentially pathogenic Streptococcus (P = .008) and Sneathia (P = .02) bacteria.

The vaginal microbiome of women with VVA was depleted, within the Lactobacillus genus, in the L. crispatus species, a hallmark of vaginal health that has significant antimicrobial activity against endogenous and exogenous pathogens.

Furthermore, there was a positive correlation between the VHI/VMI and Lactobacillus abundance (P = .002 and P = 0.035, respectively).

While the lactic acid–producing Lactobacillus and Bifidobacterium genera were strongly associated with healthy controls, the characteristics of VVA patients were strongly associated with Streptococcus, Prevotella, Alloscardovia, and Staphylococcus.

Both therapeutic approaches effectively improved vaginal indices but by different routes. Systemic hormone treatment induced changes in minority bacterial groups in the vaginal microbiome, whereas ospemifene eliminated specific harmful bacterial taxa, such as Staphylococcus (P = .04) and Clostridium (P = .01). Both treatments induced a trend in the increase of beneficial Bifidobacteria.

A 2022 study reported that vaginal estradiol tablets significantly changed the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but the reductions in bothersome symptoms were similar.
 

 

 

The future

“Areas for future study include the assessment of changes in the vaginal microbiome, proteomic profiles, and immunologic markers with various treatments and the associations between these changes and genitourinary symptoms,” Dr. Faubion said. She added that, while there may be a role at some point for oral or topical probiotics, “Thus far, probiotics have not demonstrated significant benefits.”

Meanwhile, said Ms. Murphy, “There are many options available that may benefit our patients. As a provider, meeting with your patient, discussing her concerns and individual risk factors is the most important part of choosing the correct treatment plan.”

The authors call for further studies to confirm the observed modifications of the vaginal ecosystem. In the meantime, Dr. Meriggiola said in an interview, “My best advice to physicians is to ask women if they have this problem. Do not ignore it; be proactive and treat. There are many options on the market for genitourinary symptoms – not just for postmenopausal women but breast cancer survivors as well.”

Dr. Meriggiola’s group is planning to study ospemifene in cancer patients, whose quality of life is severely affected by VVA.

This study received no financial support. Dr. Meriggiola reported past financial relationships with Shionogi Limited, Teramex, Organon, Italfarmaco, MDS Italia, and Bayer. Coauthor Dr. Baldassarre disclosed past financial relationships with Shionogi. Ms. Murphy disclosed no relevant conflicts of interest with respect to her comments. Dr. Faubion is medical director of the North American Menopause Society and editor of the journal Menopause.

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The selective estrogen receptor modulator ospemifene appears to improve the vaginal microbiome of postmenopausal women with vulvovaginal atrophy (VVA), according to results from a small Italian case-control study in the journal Menopause.

Dr. Cristina M. Meriggiola

The study sheds microbiological light on the mechanisms of ospemifene and low-dose systemic hormone therapy, which are widely used to treat genitourinary symptoms. Both had a positive effect on vaginal well-being, likely by reducing potentially harmful bacteria and increasing health-promoting acid-friendly microorganisms, writes a group led by M. Cristina Meriggiola, MD, PhD, of the gynecology and physiopathology of human reproduction unit at the University of Bologna, Italy.

Dr. Stephanie S. Faubion

VVA occurs in about 50% of postmenopausal women and produces a less favorable, less acidic vaginal microbiome profile than that of unaffected women. “The loss of estrogen leads to lower concentrations of Lactobacilli, bacteria that lower the pH. As a result, other bacterial species fill in the void,” explained Stephanie S. Faubion, MD, MBA, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Fla., and medical director of the North American Menopause Society.

Tina Murphy

Added Tina Murphy, APN, a NAMS-certified menopause practitioner at Northwestern Medicine Orland Park in Illinois, “When this protective flora declines, then pathogenic bacteria can predominate the microbiome, which can contribute to vaginal irritation, infection, UTI’s, dyspareunia, and discomfort. Balancing and restoring the microbiome can mitigate the effects of estrogen depletion on the vaginal tissue and prevent the untoward effects of the hypoestrogenic state.” While ospemifene and hormone therapy are common therapies for the genitourinary symptoms of menopause, the focus has been on their treatment efficacy, not their effect on the microbiome profile, added Dr. Faubion. Only about 9% of women with menopause-related genitourinary symptoms receive prescription treatment, she added.
 

The study

Of 67 eligible postmenopausal participants in their mid-50s enrolled at a gynecology clinic from April 2019 to February 2020, 39 were diagnosed with VVA and 28 were considered healthy controls. In the atrophic group, 20 were prescribed ospemifene and 19 received hormone treatment.

Only those women with VVA but no menopausal vasomotor symptoms received ospemifene (60 mg/day); symptomatic women received hormone therapy according to guidelines.

The researchers calculated the women’s vaginal health index (VHI) based on elasticity, secretions, pH level, epithelial mucosa, and hydration. They used swabs to assess vaginal maturation index (VMI) by percentages of superficial, intermediate, and parabasal cells. Evaluation of the vaginal microbiome was done with 16S rRNA gene sequencing, and clinical and microbiological analyses were repeated after 3 months.

The vaginal microbiome of atrophic women was characterized by a significant reduction of benign Lactobacillus bacteria (P = .002) and an increase of potentially pathogenic Streptococcus (P = .008) and Sneathia (P = .02) bacteria.

The vaginal microbiome of women with VVA was depleted, within the Lactobacillus genus, in the L. crispatus species, a hallmark of vaginal health that has significant antimicrobial activity against endogenous and exogenous pathogens.

Furthermore, there was a positive correlation between the VHI/VMI and Lactobacillus abundance (P = .002 and P = 0.035, respectively).

While the lactic acid–producing Lactobacillus and Bifidobacterium genera were strongly associated with healthy controls, the characteristics of VVA patients were strongly associated with Streptococcus, Prevotella, Alloscardovia, and Staphylococcus.

Both therapeutic approaches effectively improved vaginal indices but by different routes. Systemic hormone treatment induced changes in minority bacterial groups in the vaginal microbiome, whereas ospemifene eliminated specific harmful bacterial taxa, such as Staphylococcus (P = .04) and Clostridium (P = .01). Both treatments induced a trend in the increase of beneficial Bifidobacteria.

A 2022 study reported that vaginal estradiol tablets significantly changed the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but the reductions in bothersome symptoms were similar.
 

 

 

The future

“Areas for future study include the assessment of changes in the vaginal microbiome, proteomic profiles, and immunologic markers with various treatments and the associations between these changes and genitourinary symptoms,” Dr. Faubion said. She added that, while there may be a role at some point for oral or topical probiotics, “Thus far, probiotics have not demonstrated significant benefits.”

Meanwhile, said Ms. Murphy, “There are many options available that may benefit our patients. As a provider, meeting with your patient, discussing her concerns and individual risk factors is the most important part of choosing the correct treatment plan.”

The authors call for further studies to confirm the observed modifications of the vaginal ecosystem. In the meantime, Dr. Meriggiola said in an interview, “My best advice to physicians is to ask women if they have this problem. Do not ignore it; be proactive and treat. There are many options on the market for genitourinary symptoms – not just for postmenopausal women but breast cancer survivors as well.”

Dr. Meriggiola’s group is planning to study ospemifene in cancer patients, whose quality of life is severely affected by VVA.

This study received no financial support. Dr. Meriggiola reported past financial relationships with Shionogi Limited, Teramex, Organon, Italfarmaco, MDS Italia, and Bayer. Coauthor Dr. Baldassarre disclosed past financial relationships with Shionogi. Ms. Murphy disclosed no relevant conflicts of interest with respect to her comments. Dr. Faubion is medical director of the North American Menopause Society and editor of the journal Menopause.

The selective estrogen receptor modulator ospemifene appears to improve the vaginal microbiome of postmenopausal women with vulvovaginal atrophy (VVA), according to results from a small Italian case-control study in the journal Menopause.

Dr. Cristina M. Meriggiola

The study sheds microbiological light on the mechanisms of ospemifene and low-dose systemic hormone therapy, which are widely used to treat genitourinary symptoms. Both had a positive effect on vaginal well-being, likely by reducing potentially harmful bacteria and increasing health-promoting acid-friendly microorganisms, writes a group led by M. Cristina Meriggiola, MD, PhD, of the gynecology and physiopathology of human reproduction unit at the University of Bologna, Italy.

Dr. Stephanie S. Faubion

VVA occurs in about 50% of postmenopausal women and produces a less favorable, less acidic vaginal microbiome profile than that of unaffected women. “The loss of estrogen leads to lower concentrations of Lactobacilli, bacteria that lower the pH. As a result, other bacterial species fill in the void,” explained Stephanie S. Faubion, MD, MBA, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Fla., and medical director of the North American Menopause Society.

Tina Murphy

Added Tina Murphy, APN, a NAMS-certified menopause practitioner at Northwestern Medicine Orland Park in Illinois, “When this protective flora declines, then pathogenic bacteria can predominate the microbiome, which can contribute to vaginal irritation, infection, UTI’s, dyspareunia, and discomfort. Balancing and restoring the microbiome can mitigate the effects of estrogen depletion on the vaginal tissue and prevent the untoward effects of the hypoestrogenic state.” While ospemifene and hormone therapy are common therapies for the genitourinary symptoms of menopause, the focus has been on their treatment efficacy, not their effect on the microbiome profile, added Dr. Faubion. Only about 9% of women with menopause-related genitourinary symptoms receive prescription treatment, she added.
 

The study

Of 67 eligible postmenopausal participants in their mid-50s enrolled at a gynecology clinic from April 2019 to February 2020, 39 were diagnosed with VVA and 28 were considered healthy controls. In the atrophic group, 20 were prescribed ospemifene and 19 received hormone treatment.

Only those women with VVA but no menopausal vasomotor symptoms received ospemifene (60 mg/day); symptomatic women received hormone therapy according to guidelines.

The researchers calculated the women’s vaginal health index (VHI) based on elasticity, secretions, pH level, epithelial mucosa, and hydration. They used swabs to assess vaginal maturation index (VMI) by percentages of superficial, intermediate, and parabasal cells. Evaluation of the vaginal microbiome was done with 16S rRNA gene sequencing, and clinical and microbiological analyses were repeated after 3 months.

The vaginal microbiome of atrophic women was characterized by a significant reduction of benign Lactobacillus bacteria (P = .002) and an increase of potentially pathogenic Streptococcus (P = .008) and Sneathia (P = .02) bacteria.

The vaginal microbiome of women with VVA was depleted, within the Lactobacillus genus, in the L. crispatus species, a hallmark of vaginal health that has significant antimicrobial activity against endogenous and exogenous pathogens.

Furthermore, there was a positive correlation between the VHI/VMI and Lactobacillus abundance (P = .002 and P = 0.035, respectively).

While the lactic acid–producing Lactobacillus and Bifidobacterium genera were strongly associated with healthy controls, the characteristics of VVA patients were strongly associated with Streptococcus, Prevotella, Alloscardovia, and Staphylococcus.

Both therapeutic approaches effectively improved vaginal indices but by different routes. Systemic hormone treatment induced changes in minority bacterial groups in the vaginal microbiome, whereas ospemifene eliminated specific harmful bacterial taxa, such as Staphylococcus (P = .04) and Clostridium (P = .01). Both treatments induced a trend in the increase of beneficial Bifidobacteria.

A 2022 study reported that vaginal estradiol tablets significantly changed the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but the reductions in bothersome symptoms were similar.
 

 

 

The future

“Areas for future study include the assessment of changes in the vaginal microbiome, proteomic profiles, and immunologic markers with various treatments and the associations between these changes and genitourinary symptoms,” Dr. Faubion said. She added that, while there may be a role at some point for oral or topical probiotics, “Thus far, probiotics have not demonstrated significant benefits.”

Meanwhile, said Ms. Murphy, “There are many options available that may benefit our patients. As a provider, meeting with your patient, discussing her concerns and individual risk factors is the most important part of choosing the correct treatment plan.”

The authors call for further studies to confirm the observed modifications of the vaginal ecosystem. In the meantime, Dr. Meriggiola said in an interview, “My best advice to physicians is to ask women if they have this problem. Do not ignore it; be proactive and treat. There are many options on the market for genitourinary symptoms – not just for postmenopausal women but breast cancer survivors as well.”

Dr. Meriggiola’s group is planning to study ospemifene in cancer patients, whose quality of life is severely affected by VVA.

This study received no financial support. Dr. Meriggiola reported past financial relationships with Shionogi Limited, Teramex, Organon, Italfarmaco, MDS Italia, and Bayer. Coauthor Dr. Baldassarre disclosed past financial relationships with Shionogi. Ms. Murphy disclosed no relevant conflicts of interest with respect to her comments. Dr. Faubion is medical director of the North American Menopause Society and editor of the journal Menopause.

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