Clinical Edge Journal Scan

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2

Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).

Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P  =  .0263).

Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.

Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.

Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2

Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.

Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P  =  .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.

Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.

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

Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355

Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.

Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P  =  .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.

Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.

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

Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355

Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.

Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P  =  .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.

Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.

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

Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355

Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.

Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).

Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.

Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.

Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z

Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.

Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).

Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.

Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.

Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z

Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.

Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).

Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.

Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.

Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z

Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.

Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).

Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.

Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.

Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708

Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.

Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).

Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.

Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.

Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708

Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.

Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).

Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.

Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.

Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708

Key clinical point: The use of oral contraceptives (OC) appeared to be protective against rheumatoid arthritis (RA), whereas the use of menopausal hormone therapy (MHT) increased the risk for late-onset RA.

Major finding: Compared with never-use, ever-use (hazard ratio [HR] 0.89; 95% CI 0.82-0.96) and current-use (HR 0.81; 95% CI 0.73-0.91) of OC decreased the risk for RA, whereas ever-use (HR 1.16; 95% CI 1.06-1.26) and former-use (HR 1.13; 95% CI 1.03-1.24) of MHT increased the risk for late-onset RA.

Study details: This prospective cohort study included 239,785 British women whose data were evaluated for the effect of OC (n = 236,602) or MHT (age ≥ 60 years, n = 102,466) on RA risk.

Disclosures: This study was funded by Agnes and Mac Rudbergs Foundation (Sweden), the Åke Wiberg Foundation (Sweden), the Marcus Borgström Foundation (Sweden), and various other sources. The authors declared no conflicts of interest.

Source: Hadizadeh F et al. Effects of oral contraceptives and menopausal hormone therapy on the risk of rheumatoid arthritis: A prospective cohort study. Rheumatology (Oxford). 2023 (Sep 29). doi: 10.1093/rheumatology/kead513

Key clinical point: The use of oral contraceptives (OC) appeared to be protective against rheumatoid arthritis (RA), whereas the use of menopausal hormone therapy (MHT) increased the risk for late-onset RA.

Major finding: Compared with never-use, ever-use (hazard ratio [HR] 0.89; 95% CI 0.82-0.96) and current-use (HR 0.81; 95% CI 0.73-0.91) of OC decreased the risk for RA, whereas ever-use (HR 1.16; 95% CI 1.06-1.26) and former-use (HR 1.13; 95% CI 1.03-1.24) of MHT increased the risk for late-onset RA.

Study details: This prospective cohort study included 239,785 British women whose data were evaluated for the effect of OC (n = 236,602) or MHT (age ≥ 60 years, n = 102,466) on RA risk.

Disclosures: This study was funded by Agnes and Mac Rudbergs Foundation (Sweden), the Åke Wiberg Foundation (Sweden), the Marcus Borgström Foundation (Sweden), and various other sources. The authors declared no conflicts of interest.

Source: Hadizadeh F et al. Effects of oral contraceptives and menopausal hormone therapy on the risk of rheumatoid arthritis: A prospective cohort study. Rheumatology (Oxford). 2023 (Sep 29). doi: 10.1093/rheumatology/kead513

Key clinical point: The use of oral contraceptives (OC) appeared to be protective against rheumatoid arthritis (RA), whereas the use of menopausal hormone therapy (MHT) increased the risk for late-onset RA.

Major finding: Compared with never-use, ever-use (hazard ratio [HR] 0.89; 95% CI 0.82-0.96) and current-use (HR 0.81; 95% CI 0.73-0.91) of OC decreased the risk for RA, whereas ever-use (HR 1.16; 95% CI 1.06-1.26) and former-use (HR 1.13; 95% CI 1.03-1.24) of MHT increased the risk for late-onset RA.

Study details: This prospective cohort study included 239,785 British women whose data were evaluated for the effect of OC (n = 236,602) or MHT (age ≥ 60 years, n = 102,466) on RA risk.

Disclosures: This study was funded by Agnes and Mac Rudbergs Foundation (Sweden), the Åke Wiberg Foundation (Sweden), the Marcus Borgström Foundation (Sweden), and various other sources. The authors declared no conflicts of interest.

Source: Hadizadeh F et al. Effects of oral contraceptives and menopausal hormone therapy on the risk of rheumatoid arthritis: A prospective cohort study. Rheumatology (Oxford). 2023 (Sep 29). doi: 10.1093/rheumatology/kead513

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275