Article

Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).

Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.

Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.

Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.

Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7

Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).

Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.

Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.

Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.

Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7

Key clinical point: Patients with early rheumatoid arthritis (RA) who achieved disease remission and sustained it for 10 years had significantly lower structural progression and functional impairment than those who continued to have low disease activity (LDA).

Major finding: Patients with sustained remission vs sustained LDA had significantly lower mean 10-year structural progression (van der Heijde-modified Total Sharp Score 4.06 vs 14.59; P < .001) and 10-year functional impairment (Health Assessment Questionnaire Disability Index 0.14 vs 0.53; P < .001) scores.

Study details: This study analyzed the data of 252 patients with early RA from the ESPOIR cohort, of whom 48 patients were in sustained remission and 135 patients had sustained LDA.

Disclosures: The ESPOIR cohort was supported by grants from Merck Sharp & Dohme and other sources. The authors declared no conflicts of interest.

Source: Ruyssen-Witrand A et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207 (Oct 20). doi: 10.1186/s13075-023-03176-7

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ● 

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ● 

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ●