Clinical Edge Journal Scan

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

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.

A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.

Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.

Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.

Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.

A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.

Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.

Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.

Though rheumatoid arthritis (RA)–associated interstitial lung disease (RA-ILD) is a feared complication that can significantly affect morbidity and mortality, the role of methotrexate in treatment and its possible contribution to ILD is yet unknown. Kim and colleagues performed a retrospective analysis of a series of 170 patients with RA-ILD to try to identify risk factors and protective factors for mortality and decline of lung function. Previously known risk factors included older age, smoking, and seropositivity for cyclic citrullinated peptide (CCP). In this series, patients who had exposure to methotrexate after a diagnosis of RA-ILD were found to have less progression of decline in lung function and decreased mortality compared with those who did not, which is a finding that warrants further examination. On the other hand, there was a suggestion that sulfasalazine use is associated with increased mortality, though this finding was not borne out in multivariate analysis.

A different group of authors also examined the association with conventional disease-modifying antirheumatic drugs (DMARD) with ILD progression in a prospective analysis of 143 patients in the multicenter Korean RA-ILD cohort. Patients were classified regarding exposure to methotrexate, leflunomide, or tacrolimus as well as biologic DMARD and glucocorticoid exposure, with a primary outcome of ILD progression based on pulmonary function tests or mortality. The study did not detect any difference in time to ILD progression with methotrexate exposure, though it is not clear that the study would be able to detect a protective effect as was possible in the prior study. However, patients who were exposed to leflunomide had a shorter time to ILD progression than did those who were not, though this did not persist in multivariate analysis, and tacrolimus exposure had a statistically insignificant impact on ILD progression. Because the study is small, other associations which could affect use of leflunomide in these patients were not examined, though prior studies have suggested an association with leflunomide in ILD progression in patients with existing RA-ILD.

Li and colleagues addressed the characteristics and prognosis of late-onset RA (LORA) in people 60 years or older compared with younger-onset RA (YORA) in a prospective cohort study using a Canadian RA registry. Patients in the registry were enrolled early in the course of their illness and clinical characteristics as well as time to Disease Activity Score (DAS28) remission were analyzed. Of note, YORA and LORA patients had similar times to remission but were on less aggressive medication regimens, such as conventional DMARD without biologic DMARD or Janus kinase (JAK) inhibitors. In this registry, a smaller percentage of LORA patients compared with YORA patients were seropositive, which, given the enrollment of patients early in their disease course, may affect the use of biologic DMARD and JAK inhibitors.

Finally, the issue of noninflammatory pain contributing to disease activity and quality of life in RA has received increased scrutiny recently. Choy and colleagues studied disproportionate articular pain (DP) and its response to sarilumab, adalimumab, or placebo in a post hoc analysis of data from prior randomized clinical trials. DP was defined as a tender joint count that exceeded swollen joint count by seven and was present in about 20% of patients in the three randomized clinical trials examined. In these studies, DP was reduced in patients treated with sarilumab compared with placebo or adalimumab. Although this finding is exciting in raising the possibility of an immunologic explanation for DP via interleukin 6 (IL-6), the results should be considered carefully in the context of this post hoc analysis, especially before considering sarilumab or other IL-6 inhibitors as viable treatment options for DP in RA.

Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.

Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.

Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.

Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149

Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.

Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.

Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.

Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149

Key clinical point: The use of rituximab in patients with rheumatoid arthritis (RA) was associated with worse COVID-19 outcomes compared with the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

Major finding: The risk for COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.14; 95% CI 1.51-3.04), intensive care unit admission (aOR 5.22; 95% CI 1.77-15.41), and invasive ventilation (aOR 2.74; 95% CI 1.36-5.51) was significantly higher with baseline use of rituximab vs csDMARD.

Study details: The data come from a retrospective cohort study including 69,549 patients with RA, of which 22,956 patients were diagnosed with COVID-19 and 364 patients were exposed to rituximab prior to the first COVID-19 diagnosis.

Disclosures: This study did not report the source of funding. JA Singh reported receiving consulting fees, owning stock options, serving on speaker’s bureaus, and being a member of various committees.

Source: Singh N et al. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2022;58:152149 (Dec 8). Doi: 10.1016/j.semarthrit.2022.152149

Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).

Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).

Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.

Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184

Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).

Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).

Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.

Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184

Key clinical point: Myopenia was prevalent and associated with physical dysfunction in patients with early rheumatoid arthritis (RA).

Major finding: The prevalence of myopenia was higher in patients with early RA vs matched control individuals (41.3% vs 15.8%; P < .0167) but similar among patients with early and established RA. Myopenia was independently associated with physical dysfunction in patients with early RA (adjusted odds ratio 2.983; 95% CI 1.192-7.465).

Study details: This cross-sectional study included 1008 patients with RA (early RA n = 190; established RA n = 818) and 2017 control individuals who were age- and sex-matched for comparison.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. Two authors declared being employees of Shanghai Healthcare Co. Ltd.

Source: Pan J et al. Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis. Front Nutr. 2022;9:1007184 (Nov 23). Doi: 10.3389/fnut.2022.1007184

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.

Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).

Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.

Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.

Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.

Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).

Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.

Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.

Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA; disease onset at ≥60 years) had poor control of inflammation after diagnosis compared with those with young-onset RA (YORA), with late onset being associated with a greater cumulative inflammatory burden over time.

Major finding: Moderate-high inflammatory activity (P = .018) was more frequent in LORA vs YORA. The median C-reactive protein (P = .039) and interleukin-6 (P = .045) levels at onset were significantly higher in patients with LORA vs YORA, and late-onset was significantly associated with a high cumulative inflammatory activity of RA (odds ratio 4.694; P = .008).

Study details: This was a nested cohort study of a prospective cohort including 110 patients with incident RA (LORA n = 22; YORA n = 88) and 110 age- and sex-matched control individuals.

Disclosures: This study was supported by grants from Fondos FEDER, University of Malaga, and other sources. The authors declared no conflicts of interest.

Source: Mena-Vázquez N et al. Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study. Front Med (Lausanne). 2022;9:1016159 (Nov 8). Doi: 10.3389/fmed.2022.1016159

Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.

Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).

Study details: This was a retrospective cross-sectional study including 71 patients with RA.

Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.

Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667

Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.

Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).

Study details: This was a retrospective cross-sectional study including 71 patients with RA.

Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.

Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667

Key clinical point: Anti-protein arginine deiminase 3/4 (anti-PAD3/4) antibodies could help identify patients with rheumatoid arthritis (RA) having higher radiographic injury and bone erosion.

Major finding: Anti-PAD4 antibody levels were significantly associated with radiographic injury (P = .027). Patients with anti-PAD3/4 double positivity vs double negativity had a significantly higher radiographic injury (mean Simple Erosion Narrowing Score 48.7 vs 19.4; P = .04) and joint erosion (mean Joint Erosion Score 25.7 vs 9.3; P = .037).

Study details: This was a retrospective cross-sectional study including 71 patients with RA.

Disclosures: This study did not receive any specific funding. M Mahler and L Martinez-Prat declared being employees of Werfen, a company selling autoimmune diagnostic tests.

Source: Palterer B et al. Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Nov 28). Doi: 10.1093/rheumatology/keac667

Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.

Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.

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

Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314

Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.

Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.

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

Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314

Key clinical point: The use of methotrexate was protective against lung function decline and mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Major finding: Use of methotrexate was protective against decline in lung function (adjusted odds ratio [aOR] 0.269; P = .014) and mortality (aOR 0.284; P = .029). However, a high erythrocyte sedimentation rate at baseline was a risk factor for decline in lung function (aOR 3.056; P = .021). Age ≥65 years (aOR 2.723; P = .024) and radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (aOR 3.948; P = .005) were risk factors for mortality.

Study details: The findings are from a retrospective cohort study including 170 patients with RA-ILD who underwent at least one spirometry test and chest computed tomography scan and were treated with methotrexate or oral glucocorticoids.

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

Source: Kim K et al. Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: A retrospective cohort study. Ther Adv Respir Dis. 2022;16:17534666221135314 (Nov 8). Doi: 10.1177/17534666221135314