Clinical Edge Journal Scan

Key clinical point: A topical biotherapeutic spray containing live ammonia-oxidizing bacteria (B244) was safe and meaningfully improved pruritus at both high and low dose levels in patients with mild-to-moderate atopic dermatitis (AD) and moderate-to-severe pruritus.

Major finding: At week 4, treatment with low dose (optical density [OD] at 600 nm 5.0) and high dose (OD at 600 nm 20.0) spray vs vehicle showed a significant treatment effect (P = .015 and P = .014, respectively), with a 34% mean reduction in Worst Itch Numeric Rating Scale scores from baseline in both treatment groups. No serious adverse events were reported.

Study details: This multicenter phase 2b randomized controlled trial included 547 adult patients with mild-to-moderate AD and moderate-to-severe pruritus who were randomly assigned to receive low dose B244, high dose B244, or vehicle for 4 weeks.

Disclosures: This study was funded by AOBiome Therapeutics. Some authors reported ties with various organizations, including AOBiome. Six authors declared being current or former employees of or holding stock or  stock options in AOBiome.

Source: Silverberg JI et al. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: A randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClinicalMedicine. 2023 (May 16). doi:10.1016/j.eclinm.2023.102002

Key clinical point: A topical biotherapeutic spray containing live ammonia-oxidizing bacteria (B244) was safe and meaningfully improved pruritus at both high and low dose levels in patients with mild-to-moderate atopic dermatitis (AD) and moderate-to-severe pruritus.

Major finding: At week 4, treatment with low dose (optical density [OD] at 600 nm 5.0) and high dose (OD at 600 nm 20.0) spray vs vehicle showed a significant treatment effect (P = .015 and P = .014, respectively), with a 34% mean reduction in Worst Itch Numeric Rating Scale scores from baseline in both treatment groups. No serious adverse events were reported.

Study details: This multicenter phase 2b randomized controlled trial included 547 adult patients with mild-to-moderate AD and moderate-to-severe pruritus who were randomly assigned to receive low dose B244, high dose B244, or vehicle for 4 weeks.

Disclosures: This study was funded by AOBiome Therapeutics. Some authors reported ties with various organizations, including AOBiome. Six authors declared being current or former employees of or holding stock or  stock options in AOBiome.

Source: Silverberg JI et al. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: A randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClinicalMedicine. 2023 (May 16). doi:10.1016/j.eclinm.2023.102002

Key clinical point: A topical biotherapeutic spray containing live ammonia-oxidizing bacteria (B244) was safe and meaningfully improved pruritus at both high and low dose levels in patients with mild-to-moderate atopic dermatitis (AD) and moderate-to-severe pruritus.

Major finding: At week 4, treatment with low dose (optical density [OD] at 600 nm 5.0) and high dose (OD at 600 nm 20.0) spray vs vehicle showed a significant treatment effect (P = .015 and P = .014, respectively), with a 34% mean reduction in Worst Itch Numeric Rating Scale scores from baseline in both treatment groups. No serious adverse events were reported.

Study details: This multicenter phase 2b randomized controlled trial included 547 adult patients with mild-to-moderate AD and moderate-to-severe pruritus who were randomly assigned to receive low dose B244, high dose B244, or vehicle for 4 weeks.

Disclosures: This study was funded by AOBiome Therapeutics. Some authors reported ties with various organizations, including AOBiome. Six authors declared being current or former employees of or holding stock or  stock options in AOBiome.

Source: Silverberg JI et al. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: A randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClinicalMedicine. 2023 (May 16). doi:10.1016/j.eclinm.2023.102002

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

Several environmental risk factors are associated with the development of rheumatoid arthritis (RA), with smoking having one of the strongest associations. Exposure to airborne toxins has also been associated with development of anti–cyclic citrullinated peptide antibodies. Beidelschies and colleagues performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey to examine a potential interaction between smoking and polycyclic aromatic hydrocarbons (PAH) affecting the development of RA. Stored blood and urine samples of survey respondents were examined, and levels of PAH as well as other toxicants were measured. Of nearly 22,000 participants, about 1400 of whom reported a diagnosis of RA, toxicants were measured in about 7000. Higher levels of PAH and phthalate metabolites were more strongly associated with development of RA. Because cigarettes are a source of PAH, the authors postulated that PAH mediated the impact of smoking on development of RA, a plausible explanation given that smoking was not associated with RA after adjustment for PAH levels. However, given the cross-sectional design, causality cannot be determined.

Janus kinase (JAK) inhibitors have been found in several surveillance studies to be associated with an increased risk for cancer and cardiovascular events. Westermann and colleagues performed an observational cohort study using Danish nationwide registries to evaluate cancer risk (other than nonmelanomatous skin cancer) in patients with RA treated with tofacitinib or baricitinib. Among 875 patients treated with JAK inhibitors vs 4247 patients treated with biologic disease-modifying antirheumatic drugs (bDMARD), cancer incidence rates were similar (14.4 vs 12.9 per 1000 patient-years, respectively). Interestingly, though cancer incidence rates increased in patients > 50 and those > 65 years of age, the effect was similar between patients treated with JAK inhibitors and bDMARD. The largest difference was seen in patients up to 1 year vs > 1 year of follow-up, with hazard ratios of 1.54 vs 1.07. These findings are somewhat reassuring in light of results from the ORAL Surveillance study, suggesting increased cancer and cardiovascular risk among older patients with RA. However, as with bDMARD, increased scrutiny may be warranted among patients > 65 years, especially in the first year of treatment.

Finally, regarding withdrawal of therapy, Curtis and colleagues performed a randomized controlled study of patients with RA on combination therapy with methotrexate and etanercept and evaluated factors associated with maintenance of remission. In this study, withdrawal of methotrexate and etanercept were compared: About 250 patients whose disease was in remission, on the basis of the Simplified Disease Activity Index, were randomized in a 2:2:1 ratio to receive methotrexate monotherapy, etanercept monotherapy, or combination therapy. Prior analyses of these data have shown that continuing etanercept monotherapy showed a benefit in maintaining remission compared with continuing methotrexate monotherapy. Several baseline characteristics, including higher patient global activity at baseline and rheumatoid factor seropositivity, were associated with a lower likelihood of maintaining remission or low disease activity. Interestingly, higher serum magnesium levels seemed to negatively affect maintenance of remission, though the mechanism for this finding is not clear. In general, however, this study did not add more information to prior work in terms of shedding light on which patients may be able to stop therapy.

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴ Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

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

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

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

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

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

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600