Clinical Edge Journal Scan

• Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.

• My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.^1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.

Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.

• My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.³
• Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.

Additional References

1.         Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721   Source

2.         Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source

3.         McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source

• Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.

• My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.^1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.

Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.

• My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.³
• Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.

Additional References

1.         Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721   Source

2.         Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source

3.         McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source

• Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.

• My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.^1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.

Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.

• My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.³
• Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.

Additional References

1.         Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721   Source

2.         Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source

3.         McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.

The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.

Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.

Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.

The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.

Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.

Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.

The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.

Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

Portaccio and colleagues explored this issue and concluded that disease progression independent of relapse activity (PIRA) was a major contributor of confirmed disability accrual (CDA) in early relapse after the onset of MS, with age being a major determinant in the way that CDA occurs. In a retrospective cohort analysis of 5169 patients with either clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥ 5 years, PIRA accounted for 27.6% of disability-worsening events, whereas relapse-associated worsening accounted for 17.8% of events, with relapse-associated worsening being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients. Recognition of disease relapse or progression is not always simple in a complex disease, but failure to recognize these issues can result in long-term accumulation of economically important disability. Multiple other issues related to effective disease management also require effective juggling in routine care. Adherence to treatment, timing of DMT change, and interval between discontinuing a DMT and starting a different one continue to be critical concerns as well. Malpas and associates explored this issue and noted that the importance of adherence impact on disease control also relates to treatment interruption and timing of duration between stopping one DMT and starting another agent. The annualized relapse rate (ARR) and the rate of severe relapses was explored in a cohort of 685 people with MS and did not increase significantly after discontinuation of fingolimod in this population, but delaying the commencement of immunotherapy increased the risk for relapse. The ARR was not significantly different during and after fingolimod cessation (mean difference −0.06; 95% CI −0.14 to 0.01), with no severe relapses reported in the year prior to and after fingolimod cessation. However, delaying the recommencement of DMT, or if change in DMT was delayed from 2 to 4 months, vs beginning within 2 months (odds ratio 1.67; 95% CI 1.22-2.27) was associated with a higher risk for relapse. Discontinuation of DMT or treatment interruption also relates to planned or unplanned pregnancy in people with MS. In another study Portaccio and colleagues continued treatment with natalizumab until conception and then restarted treatment within 1 month after delivery. This reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery in women with MS. No major developmental abnormalities were noted in the infants born of 72 pregnancies in 70 women with MS who were treated for at least 2 years. Specifically, relapses occurred in 29.4% of people with MS treated until conception vs 70.2% in those who discontinued prior to conception, after a mean follow-up of 6.1 years (P = .001), with timing of treatment cessation being the only predictor of relapses (HR 4.1; P = .003). No developmental abnormalities were observed in the infants.

Practical points for the treating clinician are many and continue to highlight the complexity of managing people with MS in the real world, with real issues from COVID-19 vaccination, SARS-CoV-2 infection, recognition or awareness of relapse, and the increased challenges of adherence and timing of DMT change and of DMT use relative to pregnancy. Data-driven, reliable, relevant information is critical to incorporate into routine care to enhance and optimize decision-making.

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Key clinical point: Ultrasound (US), magnetic resonance imaging (MRI), and X-ray could differentiate psoriatic arthritis (PsA) from psoriasis and hand osteoarthritis (OA) based on the degree of structural involvement in the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC).

Major finding: US-detected new bone formation (NBF; risk ratio [RR] 0.52; P < .001) and DIP-joint synovial hypertrophy (RR 0.66; P = .005) along with PsA MRI scores (all P < .001) were associated with a lower risk for PsA vs. OA. Patients with PsA vs. psoriasis had a higher prevalence of X-ray entheseal change (mean difference 0.42; P = .024) and a higher trend toward US-detected NBF and erosions.

Study details: This prospective, cross-sectional study included 50 patients with DIP-joint PsA and nail involvement, 12 patients with psoriasis and nail involvement, and 13 patients with erosive and nonerosive OA.

Disclosures: The study was funded by Novartis, The Oak Foundation, and others. Some authors declared receiving speaker/consulting fees, research grants, or honoraria or serving as members of advisory board or consultants for several sources.

Source: Guldberg-Møller J et al. Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): A cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis. RMD Open. 2022;8:e002109 (Mar 28). Doi: 10.1136/rmdopen-2021-002109

Key clinical point: Ultrasound (US), magnetic resonance imaging (MRI), and X-ray could differentiate psoriatic arthritis (PsA) from psoriasis and hand osteoarthritis (OA) based on the degree of structural involvement in the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC).

Major finding: US-detected new bone formation (NBF; risk ratio [RR] 0.52; P < .001) and DIP-joint synovial hypertrophy (RR 0.66; P = .005) along with PsA MRI scores (all P < .001) were associated with a lower risk for PsA vs. OA. Patients with PsA vs. psoriasis had a higher prevalence of X-ray entheseal change (mean difference 0.42; P = .024) and a higher trend toward US-detected NBF and erosions.

Study details: This prospective, cross-sectional study included 50 patients with DIP-joint PsA and nail involvement, 12 patients with psoriasis and nail involvement, and 13 patients with erosive and nonerosive OA.

Disclosures: The study was funded by Novartis, The Oak Foundation, and others. Some authors declared receiving speaker/consulting fees, research grants, or honoraria or serving as members of advisory board or consultants for several sources.

Source: Guldberg-Møller J et al. Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): A cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis. RMD Open. 2022;8:e002109 (Mar 28). Doi: 10.1136/rmdopen-2021-002109

Key clinical point: Ultrasound (US), magnetic resonance imaging (MRI), and X-ray could differentiate psoriatic arthritis (PsA) from psoriasis and hand osteoarthritis (OA) based on the degree of structural involvement in the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC).

Major finding: US-detected new bone formation (NBF; risk ratio [RR] 0.52; P < .001) and DIP-joint synovial hypertrophy (RR 0.66; P = .005) along with PsA MRI scores (all P < .001) were associated with a lower risk for PsA vs. OA. Patients with PsA vs. psoriasis had a higher prevalence of X-ray entheseal change (mean difference 0.42; P = .024) and a higher trend toward US-detected NBF and erosions.

Study details: This prospective, cross-sectional study included 50 patients with DIP-joint PsA and nail involvement, 12 patients with psoriasis and nail involvement, and 13 patients with erosive and nonerosive OA.

Disclosures: The study was funded by Novartis, The Oak Foundation, and others. Some authors declared receiving speaker/consulting fees, research grants, or honoraria or serving as members of advisory board or consultants for several sources.

Source: Guldberg-Møller J et al. Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): A cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis. RMD Open. 2022;8:e002109 (Mar 28). Doi: 10.1136/rmdopen-2021-002109