Clinical Edge Journal Scan

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

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

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

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

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

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

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

The availability of biologic DMARDs such as TNF-alpha inhibitors has expanded the therapies available to patient with RA. However, these agents have been associated with immunogenicity and the development of anti-drug antibodies that can in turn be associated with allergic reactions as well as secondary non-response to the medication. This observational study analyzes the potential relationship between the presence of anti-nuclear antibodies before and after administration of different TNF-alpha inhibitors (infliximab (IFX), adalimumab (ADA), and etanercept (ADA)) with the development of anti-drug antibodies, with the aim of predicting treatment failure. Interestingly, patients who were ANA negative (by immunofluorescence) prior to initiation of therapy did not develop antibodies to ADA or IFX (antibodies to ETN were not measured). How this is related to treatment efficacy is not clear; more patients who had anti-drug antibodies discontinued therapy within 52 weeks and were classified as non-responders to therapy, but whether there was a secondary non-response was not examined in this study. As many patients with RA are also ANA positive and have SSA antibodies, these findings could potentially greatly alter treatment algorithms if proven in longer-term randomized trials and should be examined in other biologic DMARDs as well.

The Leiden Early Arthritis Cohort (EAC) is an inception cohort that was established to study inflammatory arthritis early in the disease state, with a particular interest in RA. This cross-sectional study evaluates the frequency of intermetatarsal and submetatarsal bursitis (IMB and SMB) in early RA. The presence of these forefoot disorders on MRI was evaluated in 441 consecutive patients presenting to the EAC and in 193 healthy controls. IMB and SMB were found more frequently in RA than in other inflammatory arthritides or healthy controls, with a specificity of 70-97%. Sensitivity was higher for IMB than SMB. While the study was not designed to evaluate MRI of the forefoot as a predictive test for development of RA, these findings raise the possibility that this could be used as a diagnostic test in early arthritis and would be worthwhile studying prospectively.

Another question with regard to prediction of response of RA to therapy is that of the possibility of maintaining sustained DMARD-free remission (SDFR). Another study from the Leiden EAC examined 772 RA patients treated with synthetic and biologic DMARDs who had achieved clinical remission (DAS < 2.4) without synovitis. Taper and discontinuation of therapy was attempted, and patients were followed to evaluate whether absence of synovitis on exam was sustained on followup for at least 1 year. Of these patients, 149 achieved SDFR within 7 years of followup; 130 of these patients were seronegative for ACPA. Baseline DAS was similar between patients who did and did not achieve SDFR, but a better early DAS response (larger decrease between baseline and 4 months) was associated an increased chance of SDFR. As the study is observational without a control, it is hard to evaluate how SDFR may proceed in the natural course of the disease. Although the importance of treatment response at 4 months places a premium on early reduction of inflammation, achievement of SDFR in these patients may also be related to other baseline characteristics of the group, especially as ACPA-positive patients less frequently achieved SDFR.

The availability of biologic DMARDs such as TNF-alpha inhibitors has expanded the therapies available to patient with RA. However, these agents have been associated with immunogenicity and the development of anti-drug antibodies that can in turn be associated with allergic reactions as well as secondary non-response to the medication. This observational study analyzes the potential relationship between the presence of anti-nuclear antibodies before and after administration of different TNF-alpha inhibitors (infliximab (IFX), adalimumab (ADA), and etanercept (ADA)) with the development of anti-drug antibodies, with the aim of predicting treatment failure. Interestingly, patients who were ANA negative (by immunofluorescence) prior to initiation of therapy did not develop antibodies to ADA or IFX (antibodies to ETN were not measured). How this is related to treatment efficacy is not clear; more patients who had anti-drug antibodies discontinued therapy within 52 weeks and were classified as non-responders to therapy, but whether there was a secondary non-response was not examined in this study. As many patients with RA are also ANA positive and have SSA antibodies, these findings could potentially greatly alter treatment algorithms if proven in longer-term randomized trials and should be examined in other biologic DMARDs as well.

The Leiden Early Arthritis Cohort (EAC) is an inception cohort that was established to study inflammatory arthritis early in the disease state, with a particular interest in RA. This cross-sectional study evaluates the frequency of intermetatarsal and submetatarsal bursitis (IMB and SMB) in early RA. The presence of these forefoot disorders on MRI was evaluated in 441 consecutive patients presenting to the EAC and in 193 healthy controls. IMB and SMB were found more frequently in RA than in other inflammatory arthritides or healthy controls, with a specificity of 70-97%. Sensitivity was higher for IMB than SMB. While the study was not designed to evaluate MRI of the forefoot as a predictive test for development of RA, these findings raise the possibility that this could be used as a diagnostic test in early arthritis and would be worthwhile studying prospectively.

Another question with regard to prediction of response of RA to therapy is that of the possibility of maintaining sustained DMARD-free remission (SDFR). Another study from the Leiden EAC examined 772 RA patients treated with synthetic and biologic DMARDs who had achieved clinical remission (DAS < 2.4) without synovitis. Taper and discontinuation of therapy was attempted, and patients were followed to evaluate whether absence of synovitis on exam was sustained on followup for at least 1 year. Of these patients, 149 achieved SDFR within 7 years of followup; 130 of these patients were seronegative for ACPA. Baseline DAS was similar between patients who did and did not achieve SDFR, but a better early DAS response (larger decrease between baseline and 4 months) was associated an increased chance of SDFR. As the study is observational without a control, it is hard to evaluate how SDFR may proceed in the natural course of the disease. Although the importance of treatment response at 4 months places a premium on early reduction of inflammation, achievement of SDFR in these patients may also be related to other baseline characteristics of the group, especially as ACPA-positive patients less frequently achieved SDFR.

The availability of biologic DMARDs such as TNF-alpha inhibitors has expanded the therapies available to patient with RA. However, these agents have been associated with immunogenicity and the development of anti-drug antibodies that can in turn be associated with allergic reactions as well as secondary non-response to the medication. This observational study analyzes the potential relationship between the presence of anti-nuclear antibodies before and after administration of different TNF-alpha inhibitors (infliximab (IFX), adalimumab (ADA), and etanercept (ADA)) with the development of anti-drug antibodies, with the aim of predicting treatment failure. Interestingly, patients who were ANA negative (by immunofluorescence) prior to initiation of therapy did not develop antibodies to ADA or IFX (antibodies to ETN were not measured). How this is related to treatment efficacy is not clear; more patients who had anti-drug antibodies discontinued therapy within 52 weeks and were classified as non-responders to therapy, but whether there was a secondary non-response was not examined in this study. As many patients with RA are also ANA positive and have SSA antibodies, these findings could potentially greatly alter treatment algorithms if proven in longer-term randomized trials and should be examined in other biologic DMARDs as well.

The Leiden Early Arthritis Cohort (EAC) is an inception cohort that was established to study inflammatory arthritis early in the disease state, with a particular interest in RA. This cross-sectional study evaluates the frequency of intermetatarsal and submetatarsal bursitis (IMB and SMB) in early RA. The presence of these forefoot disorders on MRI was evaluated in 441 consecutive patients presenting to the EAC and in 193 healthy controls. IMB and SMB were found more frequently in RA than in other inflammatory arthritides or healthy controls, with a specificity of 70-97%. Sensitivity was higher for IMB than SMB. While the study was not designed to evaluate MRI of the forefoot as a predictive test for development of RA, these findings raise the possibility that this could be used as a diagnostic test in early arthritis and would be worthwhile studying prospectively.

Another question with regard to prediction of response of RA to therapy is that of the possibility of maintaining sustained DMARD-free remission (SDFR). Another study from the Leiden EAC examined 772 RA patients treated with synthetic and biologic DMARDs who had achieved clinical remission (DAS < 2.4) without synovitis. Taper and discontinuation of therapy was attempted, and patients were followed to evaluate whether absence of synovitis on exam was sustained on followup for at least 1 year. Of these patients, 149 achieved SDFR within 7 years of followup; 130 of these patients were seronegative for ACPA. Baseline DAS was similar between patients who did and did not achieve SDFR, but a better early DAS response (larger decrease between baseline and 4 months) was associated an increased chance of SDFR. As the study is observational without a control, it is hard to evaluate how SDFR may proceed in the natural course of the disease. Although the importance of treatment response at 4 months places a premium on early reduction of inflammation, achievement of SDFR in these patients may also be related to other baseline characteristics of the group, especially as ACPA-positive patients less frequently achieved SDFR.

Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.

Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).

Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.

Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.

Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.

Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).

Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.

Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.

Key clinical point: Intermetatarsal (IMB) and submetatarsal (SMB) bursitis are associated with and specific for early rheumatoid arthritis (RA), with IMB having the highest sensitivity.

Major finding: IMB (adjusted odds ratio [aOR], 4.5; P less than .001) and SMB (aOR, 2.2; P = .041) were associated with RA. Sensitivity for RA of IMB and SMB was 69% and 25%, respectively. Specificity of IMB vs. other arthritides and healthy controls was 70% and 84%, respectively. Specificity for SMB was 94% (vs. other arthritides) and 97% (vs. healthy controls).

Study details: The findings are based on a large case-controlled magnetic resonance imaging study of 157 patients presenting with early RA, 284 other arthritides, and 193 healthy controls.

Disclosures: The study was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program. The authors declared no conflicts of interest.

Source: Dakkak Y et al. Arthritis Res Ther. 2020 Nov 23. doi: 10.1186/s13075-020-02359-w.