Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).

Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.

Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.

Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.

Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.

Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).

Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.

Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.

Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.

Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.

Key clinical point: Upadacitinib showed consistent improvement in signs and symptoms of psoriatic arthritis (PsA) with no new significant safety signals in patients with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).

Major finding: At 56 weeks, the proportion of patients achieving American College of Rheumatology 20/50/70 and Psoriasis Area Severity Index 75/90/100 responses was 59.7%/40.8%/24.2% and 52.3%/40.8%/26.9%, respectively, with upadacitinib 15 mg and 59.2%/38.5%/26.6% and 58.8%/47.3%/35.1%, respectively, with upadacitinib 30 mg. Improvement was consistent through the study period with both upadacitinib doses with a safety profile consistent with that known previously.

Study details: Findings are from phase 3 SELECT-PsA 2 study, involving 641 patients with PsA who had an inadequate response to at least 1 bDMARD and were randomly allocated to receive upadacitinib 15 mg, 30 mg once daily (OD), or placebo switched to upadacitinib 15 mg or 30 mg OD at week 24.

Disclosures: SELECT-PsA 2 trial was funded by AbbVie. The authors reported receiving grants/consulting fees, speaker fees from, being employees of, and stockholder from various sources including AbbVie.

Source: Mease PJ et al. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z.

Key clinical point: Patients with psoriatic arthritis (PsA) have higher adiposity and lower lean mass than healthy controls. Treatment with ustekinumab for 6-months decreased total lean mass slightly with no significant change in body composition.

Major finding: Patients with PsA had significantly lower total (P = .013) and appendicular (P = .010) lean mass and a significantly higher total fat mass and body fat percentage (both, P less than .001) compared with matched controls. After 6 months of ustekinumab treatment, total lean mass decreased significantly (P = .046) with no significant changes in body mass index.

Study details: This was a cross-sectional analysis of patients with established PsA (n=30) and matched non-PsA healthy controls (n=60). Patients with PsA who subsequently initiated ustekinumab were enrolled in a 6-month open-label follow-up study.

Disclosures: This study received an unrestricted grant from Janssen France. The authors declared no conflicts of interest.

Source: Paccou J et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24623.

Key clinical point: Patients with psoriatic arthritis (PsA) have higher adiposity and lower lean mass than healthy controls. Treatment with ustekinumab for 6-months decreased total lean mass slightly with no significant change in body composition.

Major finding: Patients with PsA had significantly lower total (P = .013) and appendicular (P = .010) lean mass and a significantly higher total fat mass and body fat percentage (both, P less than .001) compared with matched controls. After 6 months of ustekinumab treatment, total lean mass decreased significantly (P = .046) with no significant changes in body mass index.

Study details: This was a cross-sectional analysis of patients with established PsA (n=30) and matched non-PsA healthy controls (n=60). Patients with PsA who subsequently initiated ustekinumab were enrolled in a 6-month open-label follow-up study.

Disclosures: This study received an unrestricted grant from Janssen France. The authors declared no conflicts of interest.

Source: Paccou J et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24623.

Key clinical point: Patients with psoriatic arthritis (PsA) have higher adiposity and lower lean mass than healthy controls. Treatment with ustekinumab for 6-months decreased total lean mass slightly with no significant change in body composition.

Major finding: Patients with PsA had significantly lower total (P = .013) and appendicular (P = .010) lean mass and a significantly higher total fat mass and body fat percentage (both, P less than .001) compared with matched controls. After 6 months of ustekinumab treatment, total lean mass decreased significantly (P = .046) with no significant changes in body mass index.

Study details: This was a cross-sectional analysis of patients with established PsA (n=30) and matched non-PsA healthy controls (n=60). Patients with PsA who subsequently initiated ustekinumab were enrolled in a 6-month open-label follow-up study.

Disclosures: This study received an unrestricted grant from Janssen France. The authors declared no conflicts of interest.

Source: Paccou J et al. Arthritis Care Res (Hoboken). 2021 May 10. doi: 10.1002/acr.24623.

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

A version of this article first appeared on Medscape.com.

Key clinical point: Interleukin 17A inhibitor, secukinumab provides a comprehensive biologic treatment profile for management of concomitant features of psoriasis and psoriatic arthritis (PsA).

Major finding: At 52 weeks, the proportion of patients who achieved 20% or more improvement in the American College of Rheumatology response criteria was not significantly different between secukinumab and adalimumab (76.4% vs. 68.3%; P = .1752) groups. Psoriasis Area and Severity Index 90 response was higher with secukinumab vs. adalimumab (68.6% vs. 41.7%; P less than .0001).

Study details: Findings are from a prespecified analysis of 853 patients with active PsA having concomitant moderate-to-severe plaque psoriasis from phase 3b EXCEED study. Patients were randomly allocated to either subcutaneous secukinumab 300 mg (n=426) or adalimumab 40 mg (n=427).

Disclosures: EXCEED trial was funded by Novartis Pharma AG, Basel, Switzerland. The authors including the lead author reported receiving research/educational grants, consulting/speaker fees, and/or honoraria from various sources including Novartis. Three of the authors reported being employees and shareholders of Novartis.

Source: Gottlieb AB et al. Br J Dermatol. 2021 Apr 29. doi: 10.1111/bjd.20413.

Key clinical point: Interleukin 17A inhibitor, secukinumab provides a comprehensive biologic treatment profile for management of concomitant features of psoriasis and psoriatic arthritis (PsA).

Major finding: At 52 weeks, the proportion of patients who achieved 20% or more improvement in the American College of Rheumatology response criteria was not significantly different between secukinumab and adalimumab (76.4% vs. 68.3%; P = .1752) groups. Psoriasis Area and Severity Index 90 response was higher with secukinumab vs. adalimumab (68.6% vs. 41.7%; P less than .0001).

Study details: Findings are from a prespecified analysis of 853 patients with active PsA having concomitant moderate-to-severe plaque psoriasis from phase 3b EXCEED study. Patients were randomly allocated to either subcutaneous secukinumab 300 mg (n=426) or adalimumab 40 mg (n=427).

Disclosures: EXCEED trial was funded by Novartis Pharma AG, Basel, Switzerland. The authors including the lead author reported receiving research/educational grants, consulting/speaker fees, and/or honoraria from various sources including Novartis. Three of the authors reported being employees and shareholders of Novartis.

Source: Gottlieb AB et al. Br J Dermatol. 2021 Apr 29. doi: 10.1111/bjd.20413.

Key clinical point: Interleukin 17A inhibitor, secukinumab provides a comprehensive biologic treatment profile for management of concomitant features of psoriasis and psoriatic arthritis (PsA).

Major finding: At 52 weeks, the proportion of patients who achieved 20% or more improvement in the American College of Rheumatology response criteria was not significantly different between secukinumab and adalimumab (76.4% vs. 68.3%; P = .1752) groups. Psoriasis Area and Severity Index 90 response was higher with secukinumab vs. adalimumab (68.6% vs. 41.7%; P less than .0001).

Study details: Findings are from a prespecified analysis of 853 patients with active PsA having concomitant moderate-to-severe plaque psoriasis from phase 3b EXCEED study. Patients were randomly allocated to either subcutaneous secukinumab 300 mg (n=426) or adalimumab 40 mg (n=427).

Disclosures: EXCEED trial was funded by Novartis Pharma AG, Basel, Switzerland. The authors including the lead author reported receiving research/educational grants, consulting/speaker fees, and/or honoraria from various sources including Novartis. Three of the authors reported being employees and shareholders of Novartis.

Source: Gottlieb AB et al. Br J Dermatol. 2021 Apr 29. doi: 10.1111/bjd.20413.

Key clinical point: Guselkumab 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) was well tolerated in patients with psoriatic arthritis (PsA) without any new safety concerns through 1 year of DISCOVER trials.

Major finding: At 24 weeks, combined guselkumab- and placebo-treated patients showed a similar incidence of serious adverse events (SAEs; 4.4 and 7.1/100 patient-years [PY]), adverse events (AEs) leading to discontinuation of study agent (3.8 and 4.1/100 PY), infections (49.5 and 49.9/100 PY), and serious infections (1.2 and 1.7/100 PY), respectively. At 52 weeks, the time-adjusted incidence of SAEs and AEs remained stable with both guselkumab regimens.

Study details: This was a pooled analysis of phase 3 trials DISCOVER-1, and DISCOVER-2 including 1,120 patients with active PsA who had inadequate responses to standard therapies. Patients were randomly allocated to receive subcutaneous guselkumab 100 mg at week 0, then Q4W; guselkumab 100 mg at weeks 0, 4, then Q8W; or placebo at Q4W.

Disclosures: This study was funded by Janssen Research & Development, LLC.  The authors reported receiving research support, speaker bureau support, consultant fees, honoraria, and being an employee of and/or holding stocks/stock options in various sources including Janssen and Johnson & Johnson.

Source:  Rahman P et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201532.

Key clinical point: Guselkumab 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) was well tolerated in patients with psoriatic arthritis (PsA) without any new safety concerns through 1 year of DISCOVER trials.

Major finding: At 24 weeks, combined guselkumab- and placebo-treated patients showed a similar incidence of serious adverse events (SAEs; 4.4 and 7.1/100 patient-years [PY]), adverse events (AEs) leading to discontinuation of study agent (3.8 and 4.1/100 PY), infections (49.5 and 49.9/100 PY), and serious infections (1.2 and 1.7/100 PY), respectively. At 52 weeks, the time-adjusted incidence of SAEs and AEs remained stable with both guselkumab regimens.

Study details: This was a pooled analysis of phase 3 trials DISCOVER-1, and DISCOVER-2 including 1,120 patients with active PsA who had inadequate responses to standard therapies. Patients were randomly allocated to receive subcutaneous guselkumab 100 mg at week 0, then Q4W; guselkumab 100 mg at weeks 0, 4, then Q8W; or placebo at Q4W.

Disclosures: This study was funded by Janssen Research & Development, LLC.  The authors reported receiving research support, speaker bureau support, consultant fees, honoraria, and being an employee of and/or holding stocks/stock options in various sources including Janssen and Johnson & Johnson.

Source:  Rahman P et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201532.

Key clinical point: Guselkumab 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) was well tolerated in patients with psoriatic arthritis (PsA) without any new safety concerns through 1 year of DISCOVER trials.

Major finding: At 24 weeks, combined guselkumab- and placebo-treated patients showed a similar incidence of serious adverse events (SAEs; 4.4 and 7.1/100 patient-years [PY]), adverse events (AEs) leading to discontinuation of study agent (3.8 and 4.1/100 PY), infections (49.5 and 49.9/100 PY), and serious infections (1.2 and 1.7/100 PY), respectively. At 52 weeks, the time-adjusted incidence of SAEs and AEs remained stable with both guselkumab regimens.

Study details: This was a pooled analysis of phase 3 trials DISCOVER-1, and DISCOVER-2 including 1,120 patients with active PsA who had inadequate responses to standard therapies. Patients were randomly allocated to receive subcutaneous guselkumab 100 mg at week 0, then Q4W; guselkumab 100 mg at weeks 0, 4, then Q8W; or placebo at Q4W.

Disclosures: This study was funded by Janssen Research & Development, LLC.  The authors reported receiving research support, speaker bureau support, consultant fees, honoraria, and being an employee of and/or holding stocks/stock options in various sources including Janssen and Johnson & Johnson.

Source:  Rahman P et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201532.

Key clinical point: Fecal microbiota transplantation (FMT) was safe but appeared inferior to sham in reducing disease activity in patients with active peripheral psoriatic arthritis (PsA) concomitantly treated with methotrexate.

Major finding: At 6 months, the treatment failure rate was significantly higher in FMT vs. sham group (60% vs. 19%; P = .018). Improvement in Health Assessment Questionnaire Disability Index favored sham vs. FMT by 0.23 points (P = .031) while the proportion of American College of Rheumatology 20 respondents was similar (between-group difference, 0.93; 95% confidence interval, 0.45-1.94). No serious adverse events or deaths were observed.

Study details: The findings are from a 26-week, double-blind, superiority trial of 31 participants with active peripheral PsA despite ongoing treatment with methotrexate who were randomly allocated to either gastroscopic-guided FMT (n=15) or sham transplantation (n=16) into the duodenum.

Disclosures: This study was supported by the Danish Rheumatism Association, Danish Psoriasis Research Foundation, Novartis Healthcare, and others. V Andersen and R Christensen declared receiving personal fees and grants/honoraria from Merck, Janssen, and other sources.

Source: Kragsnaes MS et al. Ann Rheum Dis. 2021 Apr 29. doi: 10.1136/annrheumdis-2020-219511.

Key clinical point: Fecal microbiota transplantation (FMT) was safe but appeared inferior to sham in reducing disease activity in patients with active peripheral psoriatic arthritis (PsA) concomitantly treated with methotrexate.

Major finding: At 6 months, the treatment failure rate was significantly higher in FMT vs. sham group (60% vs. 19%; P = .018). Improvement in Health Assessment Questionnaire Disability Index favored sham vs. FMT by 0.23 points (P = .031) while the proportion of American College of Rheumatology 20 respondents was similar (between-group difference, 0.93; 95% confidence interval, 0.45-1.94). No serious adverse events or deaths were observed.

Study details: The findings are from a 26-week, double-blind, superiority trial of 31 participants with active peripheral PsA despite ongoing treatment with methotrexate who were randomly allocated to either gastroscopic-guided FMT (n=15) or sham transplantation (n=16) into the duodenum.

Disclosures: This study was supported by the Danish Rheumatism Association, Danish Psoriasis Research Foundation, Novartis Healthcare, and others. V Andersen and R Christensen declared receiving personal fees and grants/honoraria from Merck, Janssen, and other sources.

Source: Kragsnaes MS et al. Ann Rheum Dis. 2021 Apr 29. doi: 10.1136/annrheumdis-2020-219511.

Key clinical point: Fecal microbiota transplantation (FMT) was safe but appeared inferior to sham in reducing disease activity in patients with active peripheral psoriatic arthritis (PsA) concomitantly treated with methotrexate.

Major finding: At 6 months, the treatment failure rate was significantly higher in FMT vs. sham group (60% vs. 19%; P = .018). Improvement in Health Assessment Questionnaire Disability Index favored sham vs. FMT by 0.23 points (P = .031) while the proportion of American College of Rheumatology 20 respondents was similar (between-group difference, 0.93; 95% confidence interval, 0.45-1.94). No serious adverse events or deaths were observed.

Study details: The findings are from a 26-week, double-blind, superiority trial of 31 participants with active peripheral PsA despite ongoing treatment with methotrexate who were randomly allocated to either gastroscopic-guided FMT (n=15) or sham transplantation (n=16) into the duodenum.

Disclosures: This study was supported by the Danish Rheumatism Association, Danish Psoriasis Research Foundation, Novartis Healthcare, and others. V Andersen and R Christensen declared receiving personal fees and grants/honoraria from Merck, Janssen, and other sources.

Source: Kragsnaes MS et al. Ann Rheum Dis. 2021 Apr 29. doi: 10.1136/annrheumdis-2020-219511.

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

A version of this article first appeared on Medscape.com.

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

A version of this article first appeared on Medscape.com.

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

A version of this article first appeared on Medscape.com.

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com