Clinical Edge Journal Scan

Key clinical point: Adjuvant celecoxib for 2 years vs placebo fails to extend survival in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: In patients who received celecoxib vs placebo, no significant difference was observed in the disease-free survival (P = 0.75) and the overall survival (P = 0.78). In the celecoxib vs. placebo group, similar rates of cardiac events (15% vs. 13%) and new primary non-breast cancers (4% vs 4%) were reported.

Study details: A phase 3, randomized, double-blind study of patients with HER2-negative breast cancer who were randomly assigned to adjuvant celecoxib for 2 years or placebo following complete resection.

Disclosures: The study was supported by Pfizer, Cancer Research UK, The Royal Marsden NHS Foundation Trust, and the Institute of Cancer Research, London. The authors reported receiving grants, research funding, personal fees, advisory fees, nonfinancial support, and/or honoraria and/or having patents outside this work.

Source: Coombes RC et al. JAMA Oncol. 2021 Jul 15 (in press). doi: 10.1001/jamaoncol.2021.2193.

Key clinical point: Adjuvant celecoxib for 2 years vs placebo fails to extend survival in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: In patients who received celecoxib vs placebo, no significant difference was observed in the disease-free survival (P = 0.75) and the overall survival (P = 0.78). In the celecoxib vs. placebo group, similar rates of cardiac events (15% vs. 13%) and new primary non-breast cancers (4% vs 4%) were reported.

Study details: A phase 3, randomized, double-blind study of patients with HER2-negative breast cancer who were randomly assigned to adjuvant celecoxib for 2 years or placebo following complete resection.

Disclosures: The study was supported by Pfizer, Cancer Research UK, The Royal Marsden NHS Foundation Trust, and the Institute of Cancer Research, London. The authors reported receiving grants, research funding, personal fees, advisory fees, nonfinancial support, and/or honoraria and/or having patents outside this work.

Source: Coombes RC et al. JAMA Oncol. 2021 Jul 15 (in press). doi: 10.1001/jamaoncol.2021.2193.

Key clinical point: Adjuvant celecoxib for 2 years vs placebo fails to extend survival in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: In patients who received celecoxib vs placebo, no significant difference was observed in the disease-free survival (P = 0.75) and the overall survival (P = 0.78). In the celecoxib vs. placebo group, similar rates of cardiac events (15% vs. 13%) and new primary non-breast cancers (4% vs 4%) were reported.

Study details: A phase 3, randomized, double-blind study of patients with HER2-negative breast cancer who were randomly assigned to adjuvant celecoxib for 2 years or placebo following complete resection.

Disclosures: The study was supported by Pfizer, Cancer Research UK, The Royal Marsden NHS Foundation Trust, and the Institute of Cancer Research, London. The authors reported receiving grants, research funding, personal fees, advisory fees, nonfinancial support, and/or honoraria and/or having patents outside this work.

Source: Coombes RC et al. JAMA Oncol. 2021 Jul 15 (in press). doi: 10.1001/jamaoncol.2021.2193.

Key clinical point: Adding trastuzumab to chemotherapy in patients with early-stage, epidermal growth hormone receptor 2 (HER2)-positive breast cancer lowers the rate of recurrence and mortality from breast cancer.

Major finding: Trastuzumab plus chemotherapy vs chemotherapy alone significantly reduced the rates of breast cancer recurrence (rate ratio [RR], 0.66; P < 0.0001) and death from breast cancer (RR, 0.67; P < 0.0001). The average absolute reduction in 10-year risk of recurrence was 9.0% (P < 0.0001) and in 10-year breast cancer mortality was 6.4% (P < 0.0001).

Study details: This was a meta-analysis of individual patient data from 7 randomized trials including 13,864 patients with early-stage, HER2-positive breast cancer who were randomly assigned to trastuzumab plus chemotherapy or chemotherapy alone.

Disclosures: The study was funded by Cancer Research UK and the UK Medical Research Council. The authors declared grants, contracts, consulting/speaker/advisory fees, patents, royalties, and support for attending meetings and travel. Dr. H Joensuu reported a leadership/fiduciary role and stock or stock options from Orion Pharma.

Source: Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet Oncol. 2021;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6.

Key clinical point: Adding trastuzumab to chemotherapy in patients with early-stage, epidermal growth hormone receptor 2 (HER2)-positive breast cancer lowers the rate of recurrence and mortality from breast cancer.

Major finding: Trastuzumab plus chemotherapy vs chemotherapy alone significantly reduced the rates of breast cancer recurrence (rate ratio [RR], 0.66; P < 0.0001) and death from breast cancer (RR, 0.67; P < 0.0001). The average absolute reduction in 10-year risk of recurrence was 9.0% (P < 0.0001) and in 10-year breast cancer mortality was 6.4% (P < 0.0001).

Study details: This was a meta-analysis of individual patient data from 7 randomized trials including 13,864 patients with early-stage, HER2-positive breast cancer who were randomly assigned to trastuzumab plus chemotherapy or chemotherapy alone.

Disclosures: The study was funded by Cancer Research UK and the UK Medical Research Council. The authors declared grants, contracts, consulting/speaker/advisory fees, patents, royalties, and support for attending meetings and travel. Dr. H Joensuu reported a leadership/fiduciary role and stock or stock options from Orion Pharma.

Source: Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet Oncol. 2021;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6.

Key clinical point: Adding trastuzumab to chemotherapy in patients with early-stage, epidermal growth hormone receptor 2 (HER2)-positive breast cancer lowers the rate of recurrence and mortality from breast cancer.

Major finding: Trastuzumab plus chemotherapy vs chemotherapy alone significantly reduced the rates of breast cancer recurrence (rate ratio [RR], 0.66; P < 0.0001) and death from breast cancer (RR, 0.67; P < 0.0001). The average absolute reduction in 10-year risk of recurrence was 9.0% (P < 0.0001) and in 10-year breast cancer mortality was 6.4% (P < 0.0001).

Study details: This was a meta-analysis of individual patient data from 7 randomized trials including 13,864 patients with early-stage, HER2-positive breast cancer who were randomly assigned to trastuzumab plus chemotherapy or chemotherapy alone.

Disclosures: The study was funded by Cancer Research UK and the UK Medical Research Council. The authors declared grants, contracts, consulting/speaker/advisory fees, patents, royalties, and support for attending meetings and travel. Dr. H Joensuu reported a leadership/fiduciary role and stock or stock options from Orion Pharma.

Source: Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet Oncol. 2021;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6.

Key clinical point: Adding entinostat to exemestane does not improve survival in aromatase inhibitor (AI)-resistant advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: There were no differences between the entinostat and placebo groups in median progression-free survival (3.3 months vs. 3.1 months; P = 0.30) and median overall survival (23.4 months vs. 21.7 months; P = 0.94). The most common grade 3-4 adverse events in the entinostat group were neutropenia (20%) and hypophosphatemia (14%).

Study details: This was a multicenter, randomized, double-blind, placebo-controlled phase 3 E2112 study of 608 patients with AI-resistant, HR-positive, HER2-negative breast cancer, randomly assigned to entinostat plus exemestane or placebo plus exemestane.

Disclosures: The study was supported by the National Cancer Institute of the National Institutes of Health. The authors reported receiving consulting/advisory/speaker fees, research funding, accommodation/travel/expenses, and royalties from and/or stock ownership and/or other relationship in companies or patents owned/filed.

Source: Connoly RM et al. J Clin Oncol. 2021 Aug 6 (in press). doi: 10.1200/JCO.21.00944.

Key clinical point: Adding entinostat to exemestane does not improve survival in aromatase inhibitor (AI)-resistant advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: There were no differences between the entinostat and placebo groups in median progression-free survival (3.3 months vs. 3.1 months; P = 0.30) and median overall survival (23.4 months vs. 21.7 months; P = 0.94). The most common grade 3-4 adverse events in the entinostat group were neutropenia (20%) and hypophosphatemia (14%).

Study details: This was a multicenter, randomized, double-blind, placebo-controlled phase 3 E2112 study of 608 patients with AI-resistant, HR-positive, HER2-negative breast cancer, randomly assigned to entinostat plus exemestane or placebo plus exemestane.

Disclosures: The study was supported by the National Cancer Institute of the National Institutes of Health. The authors reported receiving consulting/advisory/speaker fees, research funding, accommodation/travel/expenses, and royalties from and/or stock ownership and/or other relationship in companies or patents owned/filed.

Source: Connoly RM et al. J Clin Oncol. 2021 Aug 6 (in press). doi: 10.1200/JCO.21.00944.

Key clinical point: Adding entinostat to exemestane does not improve survival in aromatase inhibitor (AI)-resistant advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Major finding: There were no differences between the entinostat and placebo groups in median progression-free survival (3.3 months vs. 3.1 months; P = 0.30) and median overall survival (23.4 months vs. 21.7 months; P = 0.94). The most common grade 3-4 adverse events in the entinostat group were neutropenia (20%) and hypophosphatemia (14%).

Study details: This was a multicenter, randomized, double-blind, placebo-controlled phase 3 E2112 study of 608 patients with AI-resistant, HR-positive, HER2-negative breast cancer, randomly assigned to entinostat plus exemestane or placebo plus exemestane.

Disclosures: The study was supported by the National Cancer Institute of the National Institutes of Health. The authors reported receiving consulting/advisory/speaker fees, research funding, accommodation/travel/expenses, and royalties from and/or stock ownership and/or other relationship in companies or patents owned/filed.

Source: Connoly RM et al. J Clin Oncol. 2021 Aug 6 (in press). doi: 10.1200/JCO.21.00944.

Key clinical point: A 10-year vs 7-year treatment with aromatase inhibitors (anastrozole) in patients with hormone receptor (HR)-positive breast cancer does not yield survival benefit but increases the risk for bone fracture.

Major finding: Anastrozole treatment for 10 years vs. 7 years was not associated with a significant difference in disease-free survival (P = 0.90). The risk of clinical bone fracture was higher with 10-year treatment (hazard ratio, 1.35; 95% confidence interval, 1.00-1.84).

Study details: The phase 3 Secondary Adjuvant Long Term Study With Arimidex  (SALSA) trial studied 3,484 postmenopausal women with HR-positive breast cancer who had received anastrozole for 5 years and were randomly assigned to therapy extension by 2 years (for a total of 7 years) or 5 years (for a total of 10 years).

Disclosures: This study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. The authors received grants, honoraria, personal/lecture/advisory/consulting/speaker fees, and/or travel/accommodation/expenses outside this work.

Source: Gnant M et al. New Engl J Med. 2021;385:395-405. doi: 10.1056/NEJMoa2104162.

Key clinical point: A 10-year vs 7-year treatment with aromatase inhibitors (anastrozole) in patients with hormone receptor (HR)-positive breast cancer does not yield survival benefit but increases the risk for bone fracture.

Major finding: Anastrozole treatment for 10 years vs. 7 years was not associated with a significant difference in disease-free survival (P = 0.90). The risk of clinical bone fracture was higher with 10-year treatment (hazard ratio, 1.35; 95% confidence interval, 1.00-1.84).

Study details: The phase 3 Secondary Adjuvant Long Term Study With Arimidex  (SALSA) trial studied 3,484 postmenopausal women with HR-positive breast cancer who had received anastrozole for 5 years and were randomly assigned to therapy extension by 2 years (for a total of 7 years) or 5 years (for a total of 10 years).

Disclosures: This study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. The authors received grants, honoraria, personal/lecture/advisory/consulting/speaker fees, and/or travel/accommodation/expenses outside this work.

Source: Gnant M et al. New Engl J Med. 2021;385:395-405. doi: 10.1056/NEJMoa2104162.

Key clinical point: A 10-year vs 7-year treatment with aromatase inhibitors (anastrozole) in patients with hormone receptor (HR)-positive breast cancer does not yield survival benefit but increases the risk for bone fracture.

Major finding: Anastrozole treatment for 10 years vs. 7 years was not associated with a significant difference in disease-free survival (P = 0.90). The risk of clinical bone fracture was higher with 10-year treatment (hazard ratio, 1.35; 95% confidence interval, 1.00-1.84).

Study details: The phase 3 Secondary Adjuvant Long Term Study With Arimidex  (SALSA) trial studied 3,484 postmenopausal women with HR-positive breast cancer who had received anastrozole for 5 years and were randomly assigned to therapy extension by 2 years (for a total of 7 years) or 5 years (for a total of 10 years).

Disclosures: This study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. The authors received grants, honoraria, personal/lecture/advisory/consulting/speaker fees, and/or travel/accommodation/expenses outside this work.

Source: Gnant M et al. New Engl J Med. 2021;385:395-405. doi: 10.1056/NEJMoa2104162.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.