Clinical Edge Journal Scan

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Key clinical point: In this real-world analysis of patients with psoriatic arthritis (PsA), interleukin-12/23 inhibitor (IL-12/23i) demonstrated longer persistence and higher adherence than tumor necrosis factor inhibitors (TNFi) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

Major finding: At 1 year, persistence was significantly longer among patients who initiated IL-12/23i vs. TNFi (269 vs. 215 days) or tsDMARD (269 vs. 213 days; both P less than .001). Adherence was significantly higher among patients who initiated IL-12/23i vs. TNFi (0.64 vs. 0.56; P = .004) or tsDMARDs (0.64 vs. 0.58; P = .027).

Study details: In this retrospective observational analysis, 7,205 patients with PsA who newly initiated a targeted immune modulator were matched (1:1) in IL-12/23i vs. TNFi (n=238), IL-12/23i vs. tsDMARD (n=238), and IL-12/23i vs. IL-17i (n=189) patient pairs.

Disclosures: This study was funded by Janssen Scientific Affairs, LLC. LA Walsh declared receiving grants and/or serving as a consultant for various pharmaceutical companies. Q Cai, I Lin, CD Pericone, and SD Chakravarty declared being current employees of Janssen Scientific Affairs, LLC and stockholders in Johnson & Johnson.

Source: Walsh JA et al. Adv Ther. 2021 Mar 23. doi: 10.1007/s12325-021-01687-w.

Key clinical point: In this real-world analysis of patients with psoriatic arthritis (PsA), interleukin-12/23 inhibitor (IL-12/23i) demonstrated longer persistence and higher adherence than tumor necrosis factor inhibitors (TNFi) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

Major finding: At 1 year, persistence was significantly longer among patients who initiated IL-12/23i vs. TNFi (269 vs. 215 days) or tsDMARD (269 vs. 213 days; both P less than .001). Adherence was significantly higher among patients who initiated IL-12/23i vs. TNFi (0.64 vs. 0.56; P = .004) or tsDMARDs (0.64 vs. 0.58; P = .027).

Study details: In this retrospective observational analysis, 7,205 patients with PsA who newly initiated a targeted immune modulator were matched (1:1) in IL-12/23i vs. TNFi (n=238), IL-12/23i vs. tsDMARD (n=238), and IL-12/23i vs. IL-17i (n=189) patient pairs.

Disclosures: This study was funded by Janssen Scientific Affairs, LLC. LA Walsh declared receiving grants and/or serving as a consultant for various pharmaceutical companies. Q Cai, I Lin, CD Pericone, and SD Chakravarty declared being current employees of Janssen Scientific Affairs, LLC and stockholders in Johnson & Johnson.

Source: Walsh JA et al. Adv Ther. 2021 Mar 23. doi: 10.1007/s12325-021-01687-w.

Key clinical point: In this real-world analysis of patients with psoriatic arthritis (PsA), interleukin-12/23 inhibitor (IL-12/23i) demonstrated longer persistence and higher adherence than tumor necrosis factor inhibitors (TNFi) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

Major finding: At 1 year, persistence was significantly longer among patients who initiated IL-12/23i vs. TNFi (269 vs. 215 days) or tsDMARD (269 vs. 213 days; both P less than .001). Adherence was significantly higher among patients who initiated IL-12/23i vs. TNFi (0.64 vs. 0.56; P = .004) or tsDMARDs (0.64 vs. 0.58; P = .027).

Study details: In this retrospective observational analysis, 7,205 patients with PsA who newly initiated a targeted immune modulator were matched (1:1) in IL-12/23i vs. TNFi (n=238), IL-12/23i vs. tsDMARD (n=238), and IL-12/23i vs. IL-17i (n=189) patient pairs.

Disclosures: This study was funded by Janssen Scientific Affairs, LLC. LA Walsh declared receiving grants and/or serving as a consultant for various pharmaceutical companies. Q Cai, I Lin, CD Pericone, and SD Chakravarty declared being current employees of Janssen Scientific Affairs, LLC and stockholders in Johnson & Johnson.

Source: Walsh JA et al. Adv Ther. 2021 Mar 23. doi: 10.1007/s12325-021-01687-w.

Key clinical point: Fatigue is a prevalent phenomenon among patients with psoriatic arthritis (PsA) and strongly correlated with quality of life (QoL), disease activity, and levels of serum interleukin-17 (IL-17).

Major finding: Level of PsA disease activity was significantly correlated with measures of fatigue, functional capacity, and QoL (P less than .001). Moreover, QoL (P = .001), disease activity (P = .019), and serum IL-17 (P = .029) were significant independent predictive factors for fatigue.

Study details: The findings come from an analysis of 80 adults with PsA from the outpatient clinics of Physical Medicine, Rheumatology, & Rehabilitation Department, Tanta University Hospitals randomly selected during the period from December 2019 to August 2020.

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

Source: Gado SE et al. Expert Rev Clin Immunol. 2021 Apr 2. doi: 10.1080/1744666X.2021.1905522.

Key clinical point: Fatigue is a prevalent phenomenon among patients with psoriatic arthritis (PsA) and strongly correlated with quality of life (QoL), disease activity, and levels of serum interleukin-17 (IL-17).

Major finding: Level of PsA disease activity was significantly correlated with measures of fatigue, functional capacity, and QoL (P less than .001). Moreover, QoL (P = .001), disease activity (P = .019), and serum IL-17 (P = .029) were significant independent predictive factors for fatigue.

Study details: The findings come from an analysis of 80 adults with PsA from the outpatient clinics of Physical Medicine, Rheumatology, & Rehabilitation Department, Tanta University Hospitals randomly selected during the period from December 2019 to August 2020.

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

Source: Gado SE et al. Expert Rev Clin Immunol. 2021 Apr 2. doi: 10.1080/1744666X.2021.1905522.

Key clinical point: Fatigue is a prevalent phenomenon among patients with psoriatic arthritis (PsA) and strongly correlated with quality of life (QoL), disease activity, and levels of serum interleukin-17 (IL-17).

Major finding: Level of PsA disease activity was significantly correlated with measures of fatigue, functional capacity, and QoL (P less than .001). Moreover, QoL (P = .001), disease activity (P = .019), and serum IL-17 (P = .029) were significant independent predictive factors for fatigue.

Study details: The findings come from an analysis of 80 adults with PsA from the outpatient clinics of Physical Medicine, Rheumatology, & Rehabilitation Department, Tanta University Hospitals randomly selected during the period from December 2019 to August 2020.

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

Source: Gado SE et al. Expert Rev Clin Immunol. 2021 Apr 2. doi: 10.1080/1744666X.2021.1905522.

Key clinical point: Among biologic-naive individuals with psoriatic arthritis (PsA), interleukin-12/23 (IL-12/23) antagonists were less effective than tumor necrosis factor-alpha (TNF-α) inhibitors. PDE4 treatment was significantly less effective than TNF-α inhibitors among biologic-experienced individuals.

Major finding: Among biologic-naïve individuals, IL-12/23 was less effective than TNF-α (adjusted relative risk [aRR], 0.63; 95% confidence interval [CI], 0.45-0.89), whereas PDE4 treatment was less effective than TNF-α inhibitor among biologic-experienced individuals (aRR, 0.67; 95% CI, 0.46-0.96).

Study details: Findings are from a retrospective study of 2,730 commercially insured and Medicare Advantage beneficiaries with PsA.

Disclosures: The authors did not declare any specific funding for this research. GC Alexander declared being Chair of FDA’s peripheral and central nervous system advisory committee, serving as a paid advisor to IQVIA, and being a consultant and holding equity in Monument Analytics. JR Curtis declared receiving consultancies and funding from pharmaceutical companies.

Source: Zhang H et al. RMD Open. 2021 Apr 16. doi: 10.1136/rmdopen-2020-001399.

Key clinical point: Among biologic-naive individuals with psoriatic arthritis (PsA), interleukin-12/23 (IL-12/23) antagonists were less effective than tumor necrosis factor-alpha (TNF-α) inhibitors. PDE4 treatment was significantly less effective than TNF-α inhibitors among biologic-experienced individuals.

Major finding: Among biologic-naïve individuals, IL-12/23 was less effective than TNF-α (adjusted relative risk [aRR], 0.63; 95% confidence interval [CI], 0.45-0.89), whereas PDE4 treatment was less effective than TNF-α inhibitor among biologic-experienced individuals (aRR, 0.67; 95% CI, 0.46-0.96).

Study details: Findings are from a retrospective study of 2,730 commercially insured and Medicare Advantage beneficiaries with PsA.

Disclosures: The authors did not declare any specific funding for this research. GC Alexander declared being Chair of FDA’s peripheral and central nervous system advisory committee, serving as a paid advisor to IQVIA, and being a consultant and holding equity in Monument Analytics. JR Curtis declared receiving consultancies and funding from pharmaceutical companies.

Source: Zhang H et al. RMD Open. 2021 Apr 16. doi: 10.1136/rmdopen-2020-001399.

Key clinical point: Among biologic-naive individuals with psoriatic arthritis (PsA), interleukin-12/23 (IL-12/23) antagonists were less effective than tumor necrosis factor-alpha (TNF-α) inhibitors. PDE4 treatment was significantly less effective than TNF-α inhibitors among biologic-experienced individuals.

Major finding: Among biologic-naïve individuals, IL-12/23 was less effective than TNF-α (adjusted relative risk [aRR], 0.63; 95% confidence interval [CI], 0.45-0.89), whereas PDE4 treatment was less effective than TNF-α inhibitor among biologic-experienced individuals (aRR, 0.67; 95% CI, 0.46-0.96).

Study details: Findings are from a retrospective study of 2,730 commercially insured and Medicare Advantage beneficiaries with PsA.

Disclosures: The authors did not declare any specific funding for this research. GC Alexander declared being Chair of FDA’s peripheral and central nervous system advisory committee, serving as a paid advisor to IQVIA, and being a consultant and holding equity in Monument Analytics. JR Curtis declared receiving consultancies and funding from pharmaceutical companies.

Source: Zhang H et al. RMD Open. 2021 Apr 16. doi: 10.1136/rmdopen-2020-001399.

Key clinical point: Clinical examination (CE) enthesitis indices should be interpreted with caution in patients with psoriatic arthritis (PsA) and concurrent fibromyalgia. Imaging including ultrasound should be preferred over CE to detect enthesitis in these patients.

Major finding: Patients with PsA with vs. without fibromyalgia had higher CE enthesitis scores (Leeds Enthesitis Index, 2.7 vs. 1.0; P less than .0001; Spondyloarthritis Research Consortium of Canada Enthesitis Index, 7.6 vs. 2.4; P less than .0001); however, ultrasound total scores (P = .87) were not different. No correlation was observed between ultrasound scores and CE enthesitis indices in patients having concurrent fibromyalgia.

Study details: Findings are from a prospective study of 106 outpatients with established PsA who underwent CE for enthesitis and ultrasonographic examination for inflammatory and structural lesions of enthesitis.

Disclosures: The authors received no financial support for research, authorship, and/or publication of the article. The authors declared no competing interests.

Source: Sapsford M et al. Ther Adv Musculoskelet Dis. 2021 Mar 29. doi: 10.1177/1759720X211003812.

Key clinical point: Clinical examination (CE) enthesitis indices should be interpreted with caution in patients with psoriatic arthritis (PsA) and concurrent fibromyalgia. Imaging including ultrasound should be preferred over CE to detect enthesitis in these patients.

Major finding: Patients with PsA with vs. without fibromyalgia had higher CE enthesitis scores (Leeds Enthesitis Index, 2.7 vs. 1.0; P less than .0001; Spondyloarthritis Research Consortium of Canada Enthesitis Index, 7.6 vs. 2.4; P less than .0001); however, ultrasound total scores (P = .87) were not different. No correlation was observed between ultrasound scores and CE enthesitis indices in patients having concurrent fibromyalgia.

Study details: Findings are from a prospective study of 106 outpatients with established PsA who underwent CE for enthesitis and ultrasonographic examination for inflammatory and structural lesions of enthesitis.

Disclosures: The authors received no financial support for research, authorship, and/or publication of the article. The authors declared no competing interests.

Source: Sapsford M et al. Ther Adv Musculoskelet Dis. 2021 Mar 29. doi: 10.1177/1759720X211003812.

Key clinical point: Clinical examination (CE) enthesitis indices should be interpreted with caution in patients with psoriatic arthritis (PsA) and concurrent fibromyalgia. Imaging including ultrasound should be preferred over CE to detect enthesitis in these patients.

Major finding: Patients with PsA with vs. without fibromyalgia had higher CE enthesitis scores (Leeds Enthesitis Index, 2.7 vs. 1.0; P less than .0001; Spondyloarthritis Research Consortium of Canada Enthesitis Index, 7.6 vs. 2.4; P less than .0001); however, ultrasound total scores (P = .87) were not different. No correlation was observed between ultrasound scores and CE enthesitis indices in patients having concurrent fibromyalgia.

Study details: Findings are from a prospective study of 106 outpatients with established PsA who underwent CE for enthesitis and ultrasonographic examination for inflammatory and structural lesions of enthesitis.

Disclosures: The authors received no financial support for research, authorship, and/or publication of the article. The authors declared no competing interests.

Source: Sapsford M et al. Ther Adv Musculoskelet Dis. 2021 Mar 29. doi: 10.1177/1759720X211003812.

Key clinical point: Patients with psoriatic arthritis (PsA) are more likely to have additional medical conditions beyond skin and joints than those with psoriasis alone.

Major finding: During follow-up, 12% of patients had an indication for PsA. Rates of comorbidities like hypertension, hyperlipidemia, fatigue, diabetes, chronic pulmonary disease, obesity, cardiovascular disease, depression, and anxiety were at least 1.1-1.7 times higher in the psoriasis-PsA vs. psoriasis-only group.

Study details: This was a retrospective study of 19,333 patients with prevalent psoriasis with no prior evidence of PsA from the United States.

Disclosures: The study was funded by UCB Pharma. R Suruki and E Lee declared being employees and shareholders of UCB Pharma. M Skornicki, P Prince, and A Louder declared being employees of Aetion Inc.

Source: Skornicki M et al. Adv Ther. 2021 Apr 5. doi: 10.1007/s12325-021-01698-7.

Key clinical point: Patients with psoriatic arthritis (PsA) are more likely to have additional medical conditions beyond skin and joints than those with psoriasis alone.

Major finding: During follow-up, 12% of patients had an indication for PsA. Rates of comorbidities like hypertension, hyperlipidemia, fatigue, diabetes, chronic pulmonary disease, obesity, cardiovascular disease, depression, and anxiety were at least 1.1-1.7 times higher in the psoriasis-PsA vs. psoriasis-only group.

Study details: This was a retrospective study of 19,333 patients with prevalent psoriasis with no prior evidence of PsA from the United States.

Disclosures: The study was funded by UCB Pharma. R Suruki and E Lee declared being employees and shareholders of UCB Pharma. M Skornicki, P Prince, and A Louder declared being employees of Aetion Inc.

Source: Skornicki M et al. Adv Ther. 2021 Apr 5. doi: 10.1007/s12325-021-01698-7.

Key clinical point: Patients with psoriatic arthritis (PsA) are more likely to have additional medical conditions beyond skin and joints than those with psoriasis alone.

Major finding: During follow-up, 12% of patients had an indication for PsA. Rates of comorbidities like hypertension, hyperlipidemia, fatigue, diabetes, chronic pulmonary disease, obesity, cardiovascular disease, depression, and anxiety were at least 1.1-1.7 times higher in the psoriasis-PsA vs. psoriasis-only group.

Study details: This was a retrospective study of 19,333 patients with prevalent psoriasis with no prior evidence of PsA from the United States.

Disclosures: The study was funded by UCB Pharma. R Suruki and E Lee declared being employees and shareholders of UCB Pharma. M Skornicki, P Prince, and A Louder declared being employees of Aetion Inc.

Source: Skornicki M et al. Adv Ther. 2021 Apr 5. doi: 10.1007/s12325-021-01698-7.

Key clinical point: Under tight settings for monitoring and treatment, women vs. men with psoriatic arthritis (PsA) had more severe disease and were less likely to achieve low disease activity (LDA), particularly if overweight.

Major finding: Women vs. men had worse mean PsA Disease Activity Score (3.5 vs. 2.7; P less than .001) and were more likely to not reach LDA (odds ratio [OR], 1.62; P = .002). Being overweight was associated with not reaching LDA (OR, 2.41-3.43; P less than .05) in women but not in men.

Study details: Findings are from secondary analysis of routine practice data of 855 outpatients with PsA who were critically monitored and treated.

Disclosures: The study was supported by the regional junior researcher grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no competing interests.

Source: Mulder MLM et al. Rheumatology (Oxford). 2021 Apr 8. doi: 10.1093/rheumatology/keab338.

Key clinical point: Under tight settings for monitoring and treatment, women vs. men with psoriatic arthritis (PsA) had more severe disease and were less likely to achieve low disease activity (LDA), particularly if overweight.

Major finding: Women vs. men had worse mean PsA Disease Activity Score (3.5 vs. 2.7; P less than .001) and were more likely to not reach LDA (odds ratio [OR], 1.62; P = .002). Being overweight was associated with not reaching LDA (OR, 2.41-3.43; P less than .05) in women but not in men.

Study details: Findings are from secondary analysis of routine practice data of 855 outpatients with PsA who were critically monitored and treated.

Disclosures: The study was supported by the regional junior researcher grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no competing interests.

Source: Mulder MLM et al. Rheumatology (Oxford). 2021 Apr 8. doi: 10.1093/rheumatology/keab338.

Key clinical point: Under tight settings for monitoring and treatment, women vs. men with psoriatic arthritis (PsA) had more severe disease and were less likely to achieve low disease activity (LDA), particularly if overweight.

Major finding: Women vs. men had worse mean PsA Disease Activity Score (3.5 vs. 2.7; P less than .001) and were more likely to not reach LDA (odds ratio [OR], 1.62; P = .002). Being overweight was associated with not reaching LDA (OR, 2.41-3.43; P less than .05) in women but not in men.

Study details: Findings are from secondary analysis of routine practice data of 855 outpatients with PsA who were critically monitored and treated.

Disclosures: The study was supported by the regional junior researcher grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no competing interests.

Source: Mulder MLM et al. Rheumatology (Oxford). 2021 Apr 8. doi: 10.1093/rheumatology/keab338.