Clinical Edge Journal Scan Commentary

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0

Recent insights into the epidemiology of atopic dermatitis

Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.

• Johansson et al¹ reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.^2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.⁵ Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.

• Paller et al⁶ recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.

I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.

Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.

• Lin et al⁷ conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.

• Medeleanu et al⁸ reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.

Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.

References

1. Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
2. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
3. Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults:  A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
4. Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
5. Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
6. Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
7. Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
8. Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).

Recent insights into the epidemiology of atopic dermatitis

Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.

• Johansson et al¹ reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.^2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.⁵ Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.

• Paller et al⁶ recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.

I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.

Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.

• Lin et al⁷ conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.

• Medeleanu et al⁸ reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.

Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.

References

1. Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
2. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
3. Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults:  A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
4. Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
5. Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
6. Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
7. Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
8. Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).

Recent insights into the epidemiology of atopic dermatitis

Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.

• Johansson et al¹ reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.^2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.⁵ Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.

• Paller et al⁶ recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.

I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.

Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.

• Lin et al⁷ conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.

• Medeleanu et al⁸ reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.

Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.

References

1. Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
2. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
3. Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults:  A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
4. Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
5. Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
6. Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
7. Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
8. Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The predilection for brain metastases in human epidermal growth factor receptor 2 (HER2)-positive breast cancer has historically presented a therapeutic challenge, and agents with enhanced central nervous system (CNS) penetrance are certainly desired. Pyrotinib is a small molecule irreversible tyrosine kinase inhibitor against epidermal growth factor receptor (EGFR), HER2, and HER4. Yan et al investigated the activity and safety of pyrotinib + capecitabine in the single-arm, two-cohort, phase 2 PERMEATE study among 78 patients with HER2-positive metastatic breast cancer (MBC) with brain metastases. The intracranial objective response rate was 74.6% in radiotherapy-naive patients and 42.1% in those progressing after prior radiotherapy. The combination showed good tolerability with the most common grade 3 treatment-related adverse events of diarrhea and neutropenia. Additional studies have shown impressive CNS activity with other HER2-targeted therapies including tucatinib + capecitabine + trastuzumab combination, as well as trastuzumab deruxtecan (HER2CLIMB and DESTINY-Breast03 trials, respectively). The evolution of these agents in both the metastatic and early settings will continue to transform the treatment algorithm for HER2-positive breast cancer. A particularly interesting concept is whether earlier use of drugs with better CNS efficacy can reduce risk or prevent development of brain metastases.

Endocrine therapy in early-stage hormone receptor-positive (HR+) breast cancer leads to significant reductions in recurrence and breast cancer mortality. A meta-analysis was performed by Early Breast Cancer Trialists' Collaborative Group including four trials (ABCSG XII, SOFT, TEXT and HOBOE), 7030 premenopausal patients with early-stage ER+ breast cancer, who received an aromatase inhibitor or tamoxifen for 3-5 years with ovarian suppression. Rates of breast cancer recurrence were lower with an aromatase inhibitor vs tamoxifen, with the main benefit seen during years 0-4 (relative risk [RR] 0.68, P < .0001) and an absolute reduction in 5-year recurrence risk of 3.2% (6.9% vs 10.1%). Aromatase inhibitor use was associated with decreased distant recurrence risk (RR 0.83), but there was no significant difference for breast cancer or all-cause mortality. The favored endocrine therapy approach for an individual patient is often complex and based on overall risk, comorbidities and toxicity concerns, as well as patient preference. Longer follow-up of trials with endocrine therapy and ovarian suppression will provide further insight on mortality impact.

Aromatase inhibitor (AI)-associated musculoskeletal symptoms are not infrequent and can contribute to treatment discontinuation. Current management practices include use of non-steroidal anti-inflammatory drugs (NSAID), weight loss and exercise, trial of alternative AI or tamoxifen, use of serotonin and norepinephrine reuptake inhibitors (SNRI) (duloxetine) and acupuncture. Martinez et al reported on outcomes of the non-selective NSAID, sulindac (150mg twice daily for 12 months), in a phase 2 study among postmenopausal women with early HR+ breast cancer who were stable on AI therapy for at least 3 months. At 12 months, patients receiving sulindac (n = 43) reported improvements (decreases) in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (-5.85, P = .003), pain (-5.40, P = .043), stiffness (-9.53, P < .001) and physical function (-5.61, P = .006); those in the observation group (n = 40) did not experience improvements in these variables. The most significant improvement with sulindac was seen in those with a higher degree of baseline symptoms and in overweight/obese patients. These findings support further investigation into abbreviated NSAID use and strategies focused on exercise and healthy body weight maintenance for breast cancer patients.

The treatment landscape for early-stage triple-negative breast cancer (TNBC) continues to evolve with integration of new drugs into our armamentarium, and use of pathologic complete response (pCR) as a surrogate for outcome and for tailoring adjuvant therapy. Geyer et al reported on event-free survival outcomes with a 4.5 year follow-up of the phase 3 BrighTNess trial, which included 634 patients with stage II-III TNBC. Significant improvement in event-free survival (EFS) was seen in the carboplatin + veliparib + paclitaxel arm vs. paclitaxel alone (HR 0.63, P = .02), but no difference in EFS in carboplatin + veliparib + paclitaxel vs. carboplatin + paclitaxel (HR 1.12, P = .62). The EFS rates at 4 years were 78% (carboplatin + veliparib + paclitaxel), 79% (carboplatin + paclitaxel) and 69% (paclitaxel alone). The phase 3 KEYNOTE-522 trial demonstrated improvement in EFS with the addition of neoadjuvant pembrolizumab to chemotherapy (carboplatin/paclitaxel followed by AC) followed by adjuvant pembrolizumab compared to chemotherapy alone in patients with stage II-III TNBC. The emergence of new therapies for early TNBC, including immunotherapy and  poly (ADP-ribose) polymerase (PARP) inhibitors (the latter for patients with germline BRCA mutations), has created more treatment options for patients along with questions regarding combinations and sequencing.  

Recommended Additional Reading:

Lin N et al. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;Spotlight Poster Session, PD4-04 Abstract 858. https://www.abstractsonline.com/pp8/#!/10462/presentation/482

Hurvitz S et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. https://www.abstractsonline.com/pp8/#!/10462/presentation/649

Rosati MS, Di Seri M, Baciarello G, et al. Etoricoxib and anastrozole in adjuvant early breast cancer: ETAN trial (phase III). J Clin Oncol. 2011;29:suppl.533. https://ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.533

Schmid P et al for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556-567. https://www.nejm.org/doi/full/10.1056/NEJMoa2112651

The predilection for brain metastases in human epidermal growth factor receptor 2 (HER2)-positive breast cancer has historically presented a therapeutic challenge, and agents with enhanced central nervous system (CNS) penetrance are certainly desired. Pyrotinib is a small molecule irreversible tyrosine kinase inhibitor against epidermal growth factor receptor (EGFR), HER2, and HER4. Yan et al investigated the activity and safety of pyrotinib + capecitabine in the single-arm, two-cohort, phase 2 PERMEATE study among 78 patients with HER2-positive metastatic breast cancer (MBC) with brain metastases. The intracranial objective response rate was 74.6% in radiotherapy-naive patients and 42.1% in those progressing after prior radiotherapy. The combination showed good tolerability with the most common grade 3 treatment-related adverse events of diarrhea and neutropenia. Additional studies have shown impressive CNS activity with other HER2-targeted therapies including tucatinib + capecitabine + trastuzumab combination, as well as trastuzumab deruxtecan (HER2CLIMB and DESTINY-Breast03 trials, respectively). The evolution of these agents in both the metastatic and early settings will continue to transform the treatment algorithm for HER2-positive breast cancer. A particularly interesting concept is whether earlier use of drugs with better CNS efficacy can reduce risk or prevent development of brain metastases.

Endocrine therapy in early-stage hormone receptor-positive (HR+) breast cancer leads to significant reductions in recurrence and breast cancer mortality. A meta-analysis was performed by Early Breast Cancer Trialists' Collaborative Group including four trials (ABCSG XII, SOFT, TEXT and HOBOE), 7030 premenopausal patients with early-stage ER+ breast cancer, who received an aromatase inhibitor or tamoxifen for 3-5 years with ovarian suppression. Rates of breast cancer recurrence were lower with an aromatase inhibitor vs tamoxifen, with the main benefit seen during years 0-4 (relative risk [RR] 0.68, P < .0001) and an absolute reduction in 5-year recurrence risk of 3.2% (6.9% vs 10.1%). Aromatase inhibitor use was associated with decreased distant recurrence risk (RR 0.83), but there was no significant difference for breast cancer or all-cause mortality. The favored endocrine therapy approach for an individual patient is often complex and based on overall risk, comorbidities and toxicity concerns, as well as patient preference. Longer follow-up of trials with endocrine therapy and ovarian suppression will provide further insight on mortality impact.

Aromatase inhibitor (AI)-associated musculoskeletal symptoms are not infrequent and can contribute to treatment discontinuation. Current management practices include use of non-steroidal anti-inflammatory drugs (NSAID), weight loss and exercise, trial of alternative AI or tamoxifen, use of serotonin and norepinephrine reuptake inhibitors (SNRI) (duloxetine) and acupuncture. Martinez et al reported on outcomes of the non-selective NSAID, sulindac (150mg twice daily for 12 months), in a phase 2 study among postmenopausal women with early HR+ breast cancer who were stable on AI therapy for at least 3 months. At 12 months, patients receiving sulindac (n = 43) reported improvements (decreases) in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (-5.85, P = .003), pain (-5.40, P = .043), stiffness (-9.53, P < .001) and physical function (-5.61, P = .006); those in the observation group (n = 40) did not experience improvements in these variables. The most significant improvement with sulindac was seen in those with a higher degree of baseline symptoms and in overweight/obese patients. These findings support further investigation into abbreviated NSAID use and strategies focused on exercise and healthy body weight maintenance for breast cancer patients.

The treatment landscape for early-stage triple-negative breast cancer (TNBC) continues to evolve with integration of new drugs into our armamentarium, and use of pathologic complete response (pCR) as a surrogate for outcome and for tailoring adjuvant therapy. Geyer et al reported on event-free survival outcomes with a 4.5 year follow-up of the phase 3 BrighTNess trial, which included 634 patients with stage II-III TNBC. Significant improvement in event-free survival (EFS) was seen in the carboplatin + veliparib + paclitaxel arm vs. paclitaxel alone (HR 0.63, P = .02), but no difference in EFS in carboplatin + veliparib + paclitaxel vs. carboplatin + paclitaxel (HR 1.12, P = .62). The EFS rates at 4 years were 78% (carboplatin + veliparib + paclitaxel), 79% (carboplatin + paclitaxel) and 69% (paclitaxel alone). The phase 3 KEYNOTE-522 trial demonstrated improvement in EFS with the addition of neoadjuvant pembrolizumab to chemotherapy (carboplatin/paclitaxel followed by AC) followed by adjuvant pembrolizumab compared to chemotherapy alone in patients with stage II-III TNBC. The emergence of new therapies for early TNBC, including immunotherapy and  poly (ADP-ribose) polymerase (PARP) inhibitors (the latter for patients with germline BRCA mutations), has created more treatment options for patients along with questions regarding combinations and sequencing.  

Recommended Additional Reading:

Lin N et al. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;Spotlight Poster Session, PD4-04 Abstract 858. https://www.abstractsonline.com/pp8/#!/10462/presentation/482

Hurvitz S et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. https://www.abstractsonline.com/pp8/#!/10462/presentation/649

Rosati MS, Di Seri M, Baciarello G, et al. Etoricoxib and anastrozole in adjuvant early breast cancer: ETAN trial (phase III). J Clin Oncol. 2011;29:suppl.533. https://ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.533

Schmid P et al for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556-567. https://www.nejm.org/doi/full/10.1056/NEJMoa2112651

The predilection for brain metastases in human epidermal growth factor receptor 2 (HER2)-positive breast cancer has historically presented a therapeutic challenge, and agents with enhanced central nervous system (CNS) penetrance are certainly desired. Pyrotinib is a small molecule irreversible tyrosine kinase inhibitor against epidermal growth factor receptor (EGFR), HER2, and HER4. Yan et al investigated the activity and safety of pyrotinib + capecitabine in the single-arm, two-cohort, phase 2 PERMEATE study among 78 patients with HER2-positive metastatic breast cancer (MBC) with brain metastases. The intracranial objective response rate was 74.6% in radiotherapy-naive patients and 42.1% in those progressing after prior radiotherapy. The combination showed good tolerability with the most common grade 3 treatment-related adverse events of diarrhea and neutropenia. Additional studies have shown impressive CNS activity with other HER2-targeted therapies including tucatinib + capecitabine + trastuzumab combination, as well as trastuzumab deruxtecan (HER2CLIMB and DESTINY-Breast03 trials, respectively). The evolution of these agents in both the metastatic and early settings will continue to transform the treatment algorithm for HER2-positive breast cancer. A particularly interesting concept is whether earlier use of drugs with better CNS efficacy can reduce risk or prevent development of brain metastases.

Endocrine therapy in early-stage hormone receptor-positive (HR+) breast cancer leads to significant reductions in recurrence and breast cancer mortality. A meta-analysis was performed by Early Breast Cancer Trialists' Collaborative Group including four trials (ABCSG XII, SOFT, TEXT and HOBOE), 7030 premenopausal patients with early-stage ER+ breast cancer, who received an aromatase inhibitor or tamoxifen for 3-5 years with ovarian suppression. Rates of breast cancer recurrence were lower with an aromatase inhibitor vs tamoxifen, with the main benefit seen during years 0-4 (relative risk [RR] 0.68, P < .0001) and an absolute reduction in 5-year recurrence risk of 3.2% (6.9% vs 10.1%). Aromatase inhibitor use was associated with decreased distant recurrence risk (RR 0.83), but there was no significant difference for breast cancer or all-cause mortality. The favored endocrine therapy approach for an individual patient is often complex and based on overall risk, comorbidities and toxicity concerns, as well as patient preference. Longer follow-up of trials with endocrine therapy and ovarian suppression will provide further insight on mortality impact.

Aromatase inhibitor (AI)-associated musculoskeletal symptoms are not infrequent and can contribute to treatment discontinuation. Current management practices include use of non-steroidal anti-inflammatory drugs (NSAID), weight loss and exercise, trial of alternative AI or tamoxifen, use of serotonin and norepinephrine reuptake inhibitors (SNRI) (duloxetine) and acupuncture. Martinez et al reported on outcomes of the non-selective NSAID, sulindac (150mg twice daily for 12 months), in a phase 2 study among postmenopausal women with early HR+ breast cancer who were stable on AI therapy for at least 3 months. At 12 months, patients receiving sulindac (n = 43) reported improvements (decreases) in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (-5.85, P = .003), pain (-5.40, P = .043), stiffness (-9.53, P < .001) and physical function (-5.61, P = .006); those in the observation group (n = 40) did not experience improvements in these variables. The most significant improvement with sulindac was seen in those with a higher degree of baseline symptoms and in overweight/obese patients. These findings support further investigation into abbreviated NSAID use and strategies focused on exercise and healthy body weight maintenance for breast cancer patients.

The treatment landscape for early-stage triple-negative breast cancer (TNBC) continues to evolve with integration of new drugs into our armamentarium, and use of pathologic complete response (pCR) as a surrogate for outcome and for tailoring adjuvant therapy. Geyer et al reported on event-free survival outcomes with a 4.5 year follow-up of the phase 3 BrighTNess trial, which included 634 patients with stage II-III TNBC. Significant improvement in event-free survival (EFS) was seen in the carboplatin + veliparib + paclitaxel arm vs. paclitaxel alone (HR 0.63, P = .02), but no difference in EFS in carboplatin + veliparib + paclitaxel vs. carboplatin + paclitaxel (HR 1.12, P = .62). The EFS rates at 4 years were 78% (carboplatin + veliparib + paclitaxel), 79% (carboplatin + paclitaxel) and 69% (paclitaxel alone). The phase 3 KEYNOTE-522 trial demonstrated improvement in EFS with the addition of neoadjuvant pembrolizumab to chemotherapy (carboplatin/paclitaxel followed by AC) followed by adjuvant pembrolizumab compared to chemotherapy alone in patients with stage II-III TNBC. The emergence of new therapies for early TNBC, including immunotherapy and  poly (ADP-ribose) polymerase (PARP) inhibitors (the latter for patients with germline BRCA mutations), has created more treatment options for patients along with questions regarding combinations and sequencing.  

Recommended Additional Reading:

Lin N et al. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;Spotlight Poster Session, PD4-04 Abstract 858. https://www.abstractsonline.com/pp8/#!/10462/presentation/482

Hurvitz S et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. https://www.abstractsonline.com/pp8/#!/10462/presentation/649

Rosati MS, Di Seri M, Baciarello G, et al. Etoricoxib and anastrozole in adjuvant early breast cancer: ETAN trial (phase III). J Clin Oncol. 2011;29:suppl.533. https://ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.533

Schmid P et al for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556-567. https://www.nejm.org/doi/full/10.1056/NEJMoa2112651

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

Many neurocognitive disorders only present a phenotype after birth. Sukenik-Halevy et al sought to examine the ability to detect prenatal phenotypes in patients with a postnatally diagnosed neurocognitive syndrome and confirmed genetic diagnosis on ES. The team was not able to identify any specific prenatal phenotype associated with their cases of postnatally diagnosed neurocognitive syndromes. The interesting finding of this study is that, of the 122 patients studied, 35.3% (43) had no abnormal sonographic findings that could have been detected prenatally to suggest the need for ES testing. ES is typically used in a prenatal setting for fetuses with anomalies that have a normal KT and CMA. The results of this study raise the question of offering ES to all patients considering diagnostic genetic testing regardless of the indication, as it may be the only way to diagnose some cases of neurocognitive disorders prenatally.

Cell-free fetal DNA (cff DNA) testing for trisomy 21, 18, and 13 has classically be used for high-risk pregnant patients seeking aneuploidy screening. Dar et al sought to examine this type of testing in a low-risk population. They studied, prospectively, the performance of cff DNA testing for trisomy 21, 18, and 13 in both low and high-risk pregnant women with confirmation of results on diagnostic genetic testing. Negative predictive values (NPV) for both the low and high-risk groups were greater than 99.9%. Positive predictive value (PPV) was lower for the low-risk group in comparison to the high-risk group, with it important to note that PPV drops from 96.4% in the high-risk group to 81.8% in the low-risk group for trisomy 21. This means that low-risk patients with a positive result on cff DNA testing are at a higher risk for a false positive than patients at high-risk for an aneuploid fetus. This study shows the mounting evidence that cff DNA can be used in a low-risk population given the high NPV. Providers do still need to note the lower PPV with low-risk population patients and always offer diagnostic genetic testing with any abnormal cff DNA test result.

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).