Clinical Edge Journal Scan

Key clinical point: Treatment with biologics significantly reduced the risk for psoriatic arthritis (PsA) development, including peripheral and axial PsA development, in patients with psoriasis.

Major finding: Patients treated at least once vs never treated with biologics had a significantly lower risk for PsA (8.9% vs 26.1%; adjusted odds ratio [aOR] 0.228; P < .001), including for peripheral PsA (aOR 0.182; P < .001) and peripheral PsA with axial involvement (aOR 0.115; P = .039). The protective effect of biologics against PsA persisted irrespective of the class of biologic used.

Study details: Findings are from an analysis of a cohort study that included 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA.

Disclosures: This study did not receive any specific funding. Four authors declared receiving consulting or speaking fees or having other ties from various sources. Other authors declared no conflicts of interest.

Source: Floris A, Mugheddu C, Sichi L, et al. Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development. Rheumatology (Oxford). 2024 (May 23). doi: 10.1093/rheumatology/keae257 Source

Key clinical point: Treatment with biologics significantly reduced the risk for psoriatic arthritis (PsA) development, including peripheral and axial PsA development, in patients with psoriasis.

Major finding: Patients treated at least once vs never treated with biologics had a significantly lower risk for PsA (8.9% vs 26.1%; adjusted odds ratio [aOR] 0.228; P < .001), including for peripheral PsA (aOR 0.182; P < .001) and peripheral PsA with axial involvement (aOR 0.115; P = .039). The protective effect of biologics against PsA persisted irrespective of the class of biologic used.

Study details: Findings are from an analysis of a cohort study that included 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA.

Disclosures: This study did not receive any specific funding. Four authors declared receiving consulting or speaking fees or having other ties from various sources. Other authors declared no conflicts of interest.

Source: Floris A, Mugheddu C, Sichi L, et al. Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development. Rheumatology (Oxford). 2024 (May 23). doi: 10.1093/rheumatology/keae257 Source

Key clinical point: Treatment with biologics significantly reduced the risk for psoriatic arthritis (PsA) development, including peripheral and axial PsA development, in patients with psoriasis.

Major finding: Patients treated at least once vs never treated with biologics had a significantly lower risk for PsA (8.9% vs 26.1%; adjusted odds ratio [aOR] 0.228; P < .001), including for peripheral PsA (aOR 0.182; P < .001) and peripheral PsA with axial involvement (aOR 0.115; P = .039). The protective effect of biologics against PsA persisted irrespective of the class of biologic used.

Study details: Findings are from an analysis of a cohort study that included 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA.

Disclosures: This study did not receive any specific funding. Four authors declared receiving consulting or speaking fees or having other ties from various sources. Other authors declared no conflicts of interest.

Source: Floris A, Mugheddu C, Sichi L, et al. Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development. Rheumatology (Oxford). 2024 (May 23). doi: 10.1093/rheumatology/keae257 Source

Key clinical point: A dose of 80 mg ixekizumab every 2 (Q2W) or 4 (Q4W) weeks demonstrated rapid and consistent efficacy, regardless of the extent of initial skin involvement in patients with psoriatic arthritis (PsA).

Major finding: In both ixekizumab treatment arms (Q2W and Q4W), over one-third of patients achieved ≥20% improvement in American College of Rheumatology (ACR)20 response as early as week 4, with the number increasing to approximately half at week 24. A similar proportion of patients achieved ACR20/50/70 response at week 24 irrespective of initial psoriasis severity (P > .05).

Study details: This post hoc subgroup analysis of SPIRIT-P1 and SPIRIT-P2 included 655 patients with active PsA and plaque psoriasis who were randomly assigned to receive placebo or 80 mg ixekizumab Q2W or Q4W.

Disclosures: The sponsorship and Rapid Service Fee for this study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. Several authors declared receiving grants or honoraria or having other ties with various sources, including Eli Lilly and Company.

Source: Armstrong AW, Jaleel T, Merola JF, et al. Ixekizumab demonstrates rapid and consistent efficacy for patients with psoriatic arthritis, regardless of psoriasis severity. Dermatol Ther (Heidelb). 2024;14:1615-1631 (May 30). Source

Key clinical point: A dose of 80 mg ixekizumab every 2 (Q2W) or 4 (Q4W) weeks demonstrated rapid and consistent efficacy, regardless of the extent of initial skin involvement in patients with psoriatic arthritis (PsA).

Major finding: In both ixekizumab treatment arms (Q2W and Q4W), over one-third of patients achieved ≥20% improvement in American College of Rheumatology (ACR)20 response as early as week 4, with the number increasing to approximately half at week 24. A similar proportion of patients achieved ACR20/50/70 response at week 24 irrespective of initial psoriasis severity (P > .05).

Study details: This post hoc subgroup analysis of SPIRIT-P1 and SPIRIT-P2 included 655 patients with active PsA and plaque psoriasis who were randomly assigned to receive placebo or 80 mg ixekizumab Q2W or Q4W.

Disclosures: The sponsorship and Rapid Service Fee for this study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. Several authors declared receiving grants or honoraria or having other ties with various sources, including Eli Lilly and Company.

Source: Armstrong AW, Jaleel T, Merola JF, et al. Ixekizumab demonstrates rapid and consistent efficacy for patients with psoriatic arthritis, regardless of psoriasis severity. Dermatol Ther (Heidelb). 2024;14:1615-1631 (May 30). Source

Key clinical point: A dose of 80 mg ixekizumab every 2 (Q2W) or 4 (Q4W) weeks demonstrated rapid and consistent efficacy, regardless of the extent of initial skin involvement in patients with psoriatic arthritis (PsA).

Major finding: In both ixekizumab treatment arms (Q2W and Q4W), over one-third of patients achieved ≥20% improvement in American College of Rheumatology (ACR)20 response as early as week 4, with the number increasing to approximately half at week 24. A similar proportion of patients achieved ACR20/50/70 response at week 24 irrespective of initial psoriasis severity (P > .05).

Study details: This post hoc subgroup analysis of SPIRIT-P1 and SPIRIT-P2 included 655 patients with active PsA and plaque psoriasis who were randomly assigned to receive placebo or 80 mg ixekizumab Q2W or Q4W.

Disclosures: The sponsorship and Rapid Service Fee for this study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. Several authors declared receiving grants or honoraria or having other ties with various sources, including Eli Lilly and Company.

Source: Armstrong AW, Jaleel T, Merola JF, et al. Ixekizumab demonstrates rapid and consistent efficacy for patients with psoriatic arthritis, regardless of psoriasis severity. Dermatol Ther (Heidelb). 2024;14:1615-1631 (May 30). Source

Key clinical point: Bimekizumab improved disease impact in a rapid and sustained manner in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD-naive) or had prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: A numerically higher proportion of bDMARD-naive patients receiving bimekizumab vs placebo achieved a clinically meaningful improvement in disease impact at week 4 (20.3% vs 2.5%) and 16 (36.8% vs 10.1%). These improvements were sustained till week 52 in patients who received bimekizumab continuously (49.0%) and in those who switched from placebo to bimekizumab (44.4%). Results were similar in the TNFi-IR subgroup.

Study details: Findings are from two phase 3 studies including 1112 patients with PsA who were bDMARD-naive or TNFi-IR and were randomly assigned to receive 160 mg bimekizumab every 4 weeks (n = 698) or placebo with crossover to bimekizumab at week 16 (n = 414).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees or shareholders of UCB Pharma. Other authors declared various ties with various sources, including UCB Pharma.

Source: Gossec L, Orbai AM, de Wit M, et al. Effect of bimekizumab on patient-reported disease impact in patients with psoriatic arthritis: 1-year results from two phase 3 studies. Rheumatology (Oxford). 2024 (May 16). doi: 10.1093/rheumatology/keae277 Source

Key clinical point: Bimekizumab improved disease impact in a rapid and sustained manner in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD-naive) or had prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: A numerically higher proportion of bDMARD-naive patients receiving bimekizumab vs placebo achieved a clinically meaningful improvement in disease impact at week 4 (20.3% vs 2.5%) and 16 (36.8% vs 10.1%). These improvements were sustained till week 52 in patients who received bimekizumab continuously (49.0%) and in those who switched from placebo to bimekizumab (44.4%). Results were similar in the TNFi-IR subgroup.

Study details: Findings are from two phase 3 studies including 1112 patients with PsA who were bDMARD-naive or TNFi-IR and were randomly assigned to receive 160 mg bimekizumab every 4 weeks (n = 698) or placebo with crossover to bimekizumab at week 16 (n = 414).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees or shareholders of UCB Pharma. Other authors declared various ties with various sources, including UCB Pharma.

Source: Gossec L, Orbai AM, de Wit M, et al. Effect of bimekizumab on patient-reported disease impact in patients with psoriatic arthritis: 1-year results from two phase 3 studies. Rheumatology (Oxford). 2024 (May 16). doi: 10.1093/rheumatology/keae277 Source

Key clinical point: Bimekizumab improved disease impact in a rapid and sustained manner in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD-naive) or had prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: A numerically higher proportion of bDMARD-naive patients receiving bimekizumab vs placebo achieved a clinically meaningful improvement in disease impact at week 4 (20.3% vs 2.5%) and 16 (36.8% vs 10.1%). These improvements were sustained till week 52 in patients who received bimekizumab continuously (49.0%) and in those who switched from placebo to bimekizumab (44.4%). Results were similar in the TNFi-IR subgroup.

Study details: Findings are from two phase 3 studies including 1112 patients with PsA who were bDMARD-naive or TNFi-IR and were randomly assigned to receive 160 mg bimekizumab every 4 weeks (n = 698) or placebo with crossover to bimekizumab at week 16 (n = 414).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees or shareholders of UCB Pharma. Other authors declared various ties with various sources, including UCB Pharma.

Source: Gossec L, Orbai AM, de Wit M, et al. Effect of bimekizumab on patient-reported disease impact in patients with psoriatic arthritis: 1-year results from two phase 3 studies. Rheumatology (Oxford). 2024 (May 16). doi: 10.1093/rheumatology/keae277 Source

Key clinical point: Risankizumab vs placebo led to higher resolution rates for enthesitis and dactylitis at 24 weeks in patients with active psoriatic arthritis (PsA), which were sustained through 52 weeks.

Major finding: At week 24, a higher proportion of risankizumab- vs placebo-treated patients achieved resolution of enthesitis (48.4% vs 34.8%; P < .001), dactylitis (68.1% vs 51.0%; P < .001), and enthesitis + dactylitis (42.2% vs 28.6%; P < .05). More than 50% of patients who continuously received risankizumab or switched from placebo to risankizumab at week 24 achieved resolution of enthesitis, dactylitis, or both.

Study details: This integrated post hoc analysis of the KEEPsAKE 1 and KEEPsAKE 2 trials included 1407 patients with PsA and previous inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs who received risankizumab or placebo with crossover to risankizumab at week 24.

Disclosures: This study was funded by AbbVie. Four authors declared being employees or holding stocks, stock options, or patents of AbbVie. Five authors declared ties with various sources, including AbbVie.

Source: Kwatra SG, Khattri S, Amin AZ, et al. Enthesitis and dactylitis resolution with risankizumab for active psoriatic arthritis: Integrated analysis of the randomized KEEPsAKE 1 and 2 trials. Dermatol Ther (Heidelb). 2024;14:1517-1530 (May 13). doi: 10.1007/s13555-024-01174-4 Source

Key clinical point: Risankizumab vs placebo led to higher resolution rates for enthesitis and dactylitis at 24 weeks in patients with active psoriatic arthritis (PsA), which were sustained through 52 weeks.

Major finding: At week 24, a higher proportion of risankizumab- vs placebo-treated patients achieved resolution of enthesitis (48.4% vs 34.8%; P < .001), dactylitis (68.1% vs 51.0%; P < .001), and enthesitis + dactylitis (42.2% vs 28.6%; P < .05). More than 50% of patients who continuously received risankizumab or switched from placebo to risankizumab at week 24 achieved resolution of enthesitis, dactylitis, or both.

Study details: This integrated post hoc analysis of the KEEPsAKE 1 and KEEPsAKE 2 trials included 1407 patients with PsA and previous inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs who received risankizumab or placebo with crossover to risankizumab at week 24.

Disclosures: This study was funded by AbbVie. Four authors declared being employees or holding stocks, stock options, or patents of AbbVie. Five authors declared ties with various sources, including AbbVie.

Source: Kwatra SG, Khattri S, Amin AZ, et al. Enthesitis and dactylitis resolution with risankizumab for active psoriatic arthritis: Integrated analysis of the randomized KEEPsAKE 1 and 2 trials. Dermatol Ther (Heidelb). 2024;14:1517-1530 (May 13). doi: 10.1007/s13555-024-01174-4 Source

Key clinical point: Risankizumab vs placebo led to higher resolution rates for enthesitis and dactylitis at 24 weeks in patients with active psoriatic arthritis (PsA), which were sustained through 52 weeks.

Major finding: At week 24, a higher proportion of risankizumab- vs placebo-treated patients achieved resolution of enthesitis (48.4% vs 34.8%; P < .001), dactylitis (68.1% vs 51.0%; P < .001), and enthesitis + dactylitis (42.2% vs 28.6%; P < .05). More than 50% of patients who continuously received risankizumab or switched from placebo to risankizumab at week 24 achieved resolution of enthesitis, dactylitis, or both.

Study details: This integrated post hoc analysis of the KEEPsAKE 1 and KEEPsAKE 2 trials included 1407 patients with PsA and previous inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs who received risankizumab or placebo with crossover to risankizumab at week 24.

Disclosures: This study was funded by AbbVie. Four authors declared being employees or holding stocks, stock options, or patents of AbbVie. Five authors declared ties with various sources, including AbbVie.

Source: Kwatra SG, Khattri S, Amin AZ, et al. Enthesitis and dactylitis resolution with risankizumab for active psoriatic arthritis: Integrated analysis of the randomized KEEPsAKE 1 and 2 trials. Dermatol Ther (Heidelb). 2024;14:1517-1530 (May 13). doi: 10.1007/s13555-024-01174-4 Source

Key clinical point: This real-world study showed that almost 1 in 6 patients with psoriatic arthritis (PsA) had potentially difficult-to-treat (D2T) disease, which was associated with extensive psoriasis, higher body mass index (BMI), and a history of inflammatory bowel disease (IBD).

Major finding: Of 467 patients, 16.5% had D2T PsA. Compared to non-D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis (odds ratio [OR] 5.05; P < .0001), higher BMI (OR 1.07; P = .023), and a history of IBD (OR 1.22; P = .026).

Study details: This study analyzed 467 patients with PsA from a Greek registry who had ≥6-months of disease duration, progressed on disease modifying anti-rheumatic drugs with different mechanisms of actions, and had disease activity index for PsA > 14 or were not at minimal disease activity.

Disclosures: The registry was funded by the Greek (Hellenic) Rheumatology Society. The authors declared no conflicts of interest.

Source: Vassilakis KD, Papagoras C, Fytanidis N, et al. Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: Exploratory analyses of the Greek PsA registry. Rheumatology (Oxford). 2024 (May 17). doi: 10.1093/rheumatology/keae263 Source

Key clinical point: This real-world study showed that almost 1 in 6 patients with psoriatic arthritis (PsA) had potentially difficult-to-treat (D2T) disease, which was associated with extensive psoriasis, higher body mass index (BMI), and a history of inflammatory bowel disease (IBD).

Major finding: Of 467 patients, 16.5% had D2T PsA. Compared to non-D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis (odds ratio [OR] 5.05; P < .0001), higher BMI (OR 1.07; P = .023), and a history of IBD (OR 1.22; P = .026).

Study details: This study analyzed 467 patients with PsA from a Greek registry who had ≥6-months of disease duration, progressed on disease modifying anti-rheumatic drugs with different mechanisms of actions, and had disease activity index for PsA > 14 or were not at minimal disease activity.

Disclosures: The registry was funded by the Greek (Hellenic) Rheumatology Society. The authors declared no conflicts of interest.

Source: Vassilakis KD, Papagoras C, Fytanidis N, et al. Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: Exploratory analyses of the Greek PsA registry. Rheumatology (Oxford). 2024 (May 17). doi: 10.1093/rheumatology/keae263 Source

Key clinical point: This real-world study showed that almost 1 in 6 patients with psoriatic arthritis (PsA) had potentially difficult-to-treat (D2T) disease, which was associated with extensive psoriasis, higher body mass index (BMI), and a history of inflammatory bowel disease (IBD).

Major finding: Of 467 patients, 16.5% had D2T PsA. Compared to non-D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis (odds ratio [OR] 5.05; P < .0001), higher BMI (OR 1.07; P = .023), and a history of IBD (OR 1.22; P = .026).

Study details: This study analyzed 467 patients with PsA from a Greek registry who had ≥6-months of disease duration, progressed on disease modifying anti-rheumatic drugs with different mechanisms of actions, and had disease activity index for PsA > 14 or were not at minimal disease activity.

Disclosures: The registry was funded by the Greek (Hellenic) Rheumatology Society. The authors declared no conflicts of interest.

Source: Vassilakis KD, Papagoras C, Fytanidis N, et al. Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: Exploratory analyses of the Greek PsA registry. Rheumatology (Oxford). 2024 (May 17). doi: 10.1093/rheumatology/keae263 Source

Key clinical point: Low stress resilience during adolescence increased the risk of developing psoriatic arthritis (PsA) later in life in a cohort of >1.6 million men who were followed up for up to 51 years.

Major finding: Over nearly 51 years of follow-up, 9433 (0.6%) men developed first onset PsA. Low vs high stress resilience increased the risk for new-onset PsA by 23% in the overall cohort (adjusted hazard ratio [aHR] 1.23; 95% CI 1.15-1.32) and 53% in the subgroup of patients who were hospitalized due to severe PsA (aHR 1.53; 95% CI 1.32-1.77).

Study details: This prospective cohort study included 1,669,422 men from the Swedish Military Service Conscription Register, of whom 20.4%, 58.0%, and 21.5% had low, medium, and high stress resilience levels, respectively.

Disclosures: This study was supported by the Swedish Research Council for Health and other sources. One author declared receiving honoraria as consultant or speaker from various sources. Other authors declared no conflicts of interest.

Source: Laskowski M, Schiöler L, Åberg M, et al. Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden. J Eur Acad Dermatol Venereol. 2024 (May 20). doi: 10.1111/jdv.20069 Source

Key clinical point: Low stress resilience during adolescence increased the risk of developing psoriatic arthritis (PsA) later in life in a cohort of >1.6 million men who were followed up for up to 51 years.

Major finding: Over nearly 51 years of follow-up, 9433 (0.6%) men developed first onset PsA. Low vs high stress resilience increased the risk for new-onset PsA by 23% in the overall cohort (adjusted hazard ratio [aHR] 1.23; 95% CI 1.15-1.32) and 53% in the subgroup of patients who were hospitalized due to severe PsA (aHR 1.53; 95% CI 1.32-1.77).

Study details: This prospective cohort study included 1,669,422 men from the Swedish Military Service Conscription Register, of whom 20.4%, 58.0%, and 21.5% had low, medium, and high stress resilience levels, respectively.

Disclosures: This study was supported by the Swedish Research Council for Health and other sources. One author declared receiving honoraria as consultant or speaker from various sources. Other authors declared no conflicts of interest.

Source: Laskowski M, Schiöler L, Åberg M, et al. Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden. J Eur Acad Dermatol Venereol. 2024 (May 20). doi: 10.1111/jdv.20069 Source

Key clinical point: Low stress resilience during adolescence increased the risk of developing psoriatic arthritis (PsA) later in life in a cohort of >1.6 million men who were followed up for up to 51 years.

Major finding: Over nearly 51 years of follow-up, 9433 (0.6%) men developed first onset PsA. Low vs high stress resilience increased the risk for new-onset PsA by 23% in the overall cohort (adjusted hazard ratio [aHR] 1.23; 95% CI 1.15-1.32) and 53% in the subgroup of patients who were hospitalized due to severe PsA (aHR 1.53; 95% CI 1.32-1.77).

Study details: This prospective cohort study included 1,669,422 men from the Swedish Military Service Conscription Register, of whom 20.4%, 58.0%, and 21.5% had low, medium, and high stress resilience levels, respectively.

Disclosures: This study was supported by the Swedish Research Council for Health and other sources. One author declared receiving honoraria as consultant or speaker from various sources. Other authors declared no conflicts of interest.

Source: Laskowski M, Schiöler L, Åberg M, et al. Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden. J Eur Acad Dermatol Venereol. 2024 (May 20). doi: 10.1111/jdv.20069 Source

In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.

Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg  with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.

In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.

Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg  with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.

In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.

Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg  with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

The postpartum period represents a possibly vulnerable time window for development of new cancers with metastatic potential. Studies in young-onset breast cancer have shown a postpartum diagnosis up to 10 years after childbirth associated with adverse breast cancer survival outcomes.⁴ Women with germline BRCA1/2 pathogenic variants have a higher risk of developing breast cancer at a younger age compared to the general population.⁵ A prospective cohort study that included 903 women with germline BRCA1/2 mutations diagnosed with stage I-III breast cancer at age ≤ 45 years investigated whether time since childbirth and time since breast cancer diagnosis were associated with mortality in this population (). A total of 419 women were diagnosed with breast cancer 0-10 years after childbirth (228 at <5 years and 191 at 5-10 years) and 224 women were nulliparous. Breast cancer diagnosis 5 to <10 years postpartum was associated with higher mortality risk vs nulliparous women (adjusted hazard ratio 1.56, 95% CI 1.05-2.03; P = .03), with a more pronounced effect seen among those with estrogen receptor–negative disease (hazard ratio 3.12; 95% CI 1.22-7.97; P = .02) and BRCA1 carriers (hazard ratio 2.03; 95% CI 1.15-3.58; P = .02). This study highlights the importance of appropriate counseling for BRCA1/2 mutation carriers, with efforts aimed at optimizing prevention and treatment strategies in young-onset breast cancer.

The mechanisms involved in development of endocrine therapy (ET) resistance are complex and may include changes in hormone signaling, alterations in growth factor signaling pathway components, and appearance of resistant clonal populations.⁶ Prior studies have shown efficacy with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with various ET backbones. However, the sequencing of these combinations in current clinical practice has shifted in light of significant therapeutic advancements in this space.⁷ A retrospective observational study including 161 patients with advanced hormone receptor–positive (HR+)/ human epidermal growth factor receptor–2 negative (HER2-) breast cancer treated with everolimus plus ET (exemestane, fulvestrant, tamoxifen) reported outcomes on the real-world use of these regimens after progression on cyclin-dependent kinase (CDK) 4/6 inhibitor therapy (Sánchez-Bayona et al). At a median follow-up of 15 months, the estimated median progression-free survival (PFS) was 6.0 months (95% CI 5.3-7.8 months); PFS was longer among those with previous CDK4/6 inhibitor use lasting >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral disease (8.0 months; 95% CI 5.8-10.5 months), and those who were chemotherapy-naive in the advanced setting (7.2 months; 95% CI 5.9-8.4 months). These data support a role for everolimus plus ET as a treatment option post–CDK4/6 inhibitor treatment for selected patient populations, including those whose tumors lack targetable somatic mutations (such as PIK3CA and ESR1 mutations), and may provide meaningful clinical benefit in this setting.

Additional References

1. Rothwell PM, Wilson M, Price JF,  et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591-601. doi: 10.1016/S0140-6736(12)60209-8 Source
2. Okada S, Morimoto T, Ogawa H, et al, and the JPAD Trial Investigators. Effect of aspirin on cancer chemoprevention in Japanese patients with type 2 diabetes: 10-year observational follow-up of a randomized controlled trial. Diabetes Care. 2018;41:1757-1764. doi: 10.2337/dc18-0368 Source
3. Burn J, Sheth H, Elliott F, et al, on behalf of the CAPP2 Investigators. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: A double-blind, randomised, placebo-controlled trial. Lancet. 2020;395:1855-1863. doi: 10.1016/S0140-6736(20)30366-4 Source
4. Shao C, Yu Z, Xiao J, et al. Prognosis of pregnancy-associated breast cancer: A meta-analysis. BMC Cancer. 2020;20:746. doi: 10.1186/s12885-020-07248-8 Source
5. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402-2416. doi: 10.1001/jama.2017.7112 Source
6. Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37:496-513. doi: 10.1016/j.ccell.2020.03.009 Source
7. Kornblum N, Zhao F, Manola J, et al. Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: Results of PrE0102. J Clin Oncol. 2018;36:1556-1563. doi: 10.1200/JCO.2017.76.9331 Source

The postpartum period represents a possibly vulnerable time window for development of new cancers with metastatic potential. Studies in young-onset breast cancer have shown a postpartum diagnosis up to 10 years after childbirth associated with adverse breast cancer survival outcomes.⁴ Women with germline BRCA1/2 pathogenic variants have a higher risk of developing breast cancer at a younger age compared to the general population.⁵ A prospective cohort study that included 903 women with germline BRCA1/2 mutations diagnosed with stage I-III breast cancer at age ≤ 45 years investigated whether time since childbirth and time since breast cancer diagnosis were associated with mortality in this population (). A total of 419 women were diagnosed with breast cancer 0-10 years after childbirth (228 at <5 years and 191 at 5-10 years) and 224 women were nulliparous. Breast cancer diagnosis 5 to <10 years postpartum was associated with higher mortality risk vs nulliparous women (adjusted hazard ratio 1.56, 95% CI 1.05-2.03; P = .03), with a more pronounced effect seen among those with estrogen receptor–negative disease (hazard ratio 3.12; 95% CI 1.22-7.97; P = .02) and BRCA1 carriers (hazard ratio 2.03; 95% CI 1.15-3.58; P = .02). This study highlights the importance of appropriate counseling for BRCA1/2 mutation carriers, with efforts aimed at optimizing prevention and treatment strategies in young-onset breast cancer.

The mechanisms involved in development of endocrine therapy (ET) resistance are complex and may include changes in hormone signaling, alterations in growth factor signaling pathway components, and appearance of resistant clonal populations.⁶ Prior studies have shown efficacy with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with various ET backbones. However, the sequencing of these combinations in current clinical practice has shifted in light of significant therapeutic advancements in this space.⁷ A retrospective observational study including 161 patients with advanced hormone receptor–positive (HR+)/ human epidermal growth factor receptor–2 negative (HER2-) breast cancer treated with everolimus plus ET (exemestane, fulvestrant, tamoxifen) reported outcomes on the real-world use of these regimens after progression on cyclin-dependent kinase (CDK) 4/6 inhibitor therapy (Sánchez-Bayona et al). At a median follow-up of 15 months, the estimated median progression-free survival (PFS) was 6.0 months (95% CI 5.3-7.8 months); PFS was longer among those with previous CDK4/6 inhibitor use lasting >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral disease (8.0 months; 95% CI 5.8-10.5 months), and those who were chemotherapy-naive in the advanced setting (7.2 months; 95% CI 5.9-8.4 months). These data support a role for everolimus plus ET as a treatment option post–CDK4/6 inhibitor treatment for selected patient populations, including those whose tumors lack targetable somatic mutations (such as PIK3CA and ESR1 mutations), and may provide meaningful clinical benefit in this setting.

Additional References

1. Rothwell PM, Wilson M, Price JF,  et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591-601. doi: 10.1016/S0140-6736(12)60209-8 Source
2. Okada S, Morimoto T, Ogawa H, et al, and the JPAD Trial Investigators. Effect of aspirin on cancer chemoprevention in Japanese patients with type 2 diabetes: 10-year observational follow-up of a randomized controlled trial. Diabetes Care. 2018;41:1757-1764. doi: 10.2337/dc18-0368 Source
3. Burn J, Sheth H, Elliott F, et al, on behalf of the CAPP2 Investigators. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: A double-blind, randomised, placebo-controlled trial. Lancet. 2020;395:1855-1863. doi: 10.1016/S0140-6736(20)30366-4 Source
4. Shao C, Yu Z, Xiao J, et al. Prognosis of pregnancy-associated breast cancer: A meta-analysis. BMC Cancer. 2020;20:746. doi: 10.1186/s12885-020-07248-8 Source
5. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402-2416. doi: 10.1001/jama.2017.7112 Source
6. Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37:496-513. doi: 10.1016/j.ccell.2020.03.009 Source
7. Kornblum N, Zhao F, Manola J, et al. Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: Results of PrE0102. J Clin Oncol. 2018;36:1556-1563. doi: 10.1200/JCO.2017.76.9331 Source

The postpartum period represents a possibly vulnerable time window for development of new cancers with metastatic potential. Studies in young-onset breast cancer have shown a postpartum diagnosis up to 10 years after childbirth associated with adverse breast cancer survival outcomes.⁴ Women with germline BRCA1/2 pathogenic variants have a higher risk of developing breast cancer at a younger age compared to the general population.⁵ A prospective cohort study that included 903 women with germline BRCA1/2 mutations diagnosed with stage I-III breast cancer at age ≤ 45 years investigated whether time since childbirth and time since breast cancer diagnosis were associated with mortality in this population (). A total of 419 women were diagnosed with breast cancer 0-10 years after childbirth (228 at <5 years and 191 at 5-10 years) and 224 women were nulliparous. Breast cancer diagnosis 5 to <10 years postpartum was associated with higher mortality risk vs nulliparous women (adjusted hazard ratio 1.56, 95% CI 1.05-2.03; P = .03), with a more pronounced effect seen among those with estrogen receptor–negative disease (hazard ratio 3.12; 95% CI 1.22-7.97; P = .02) and BRCA1 carriers (hazard ratio 2.03; 95% CI 1.15-3.58; P = .02). This study highlights the importance of appropriate counseling for BRCA1/2 mutation carriers, with efforts aimed at optimizing prevention and treatment strategies in young-onset breast cancer.

The mechanisms involved in development of endocrine therapy (ET) resistance are complex and may include changes in hormone signaling, alterations in growth factor signaling pathway components, and appearance of resistant clonal populations.⁶ Prior studies have shown efficacy with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with various ET backbones. However, the sequencing of these combinations in current clinical practice has shifted in light of significant therapeutic advancements in this space.⁷ A retrospective observational study including 161 patients with advanced hormone receptor–positive (HR+)/ human epidermal growth factor receptor–2 negative (HER2-) breast cancer treated with everolimus plus ET (exemestane, fulvestrant, tamoxifen) reported outcomes on the real-world use of these regimens after progression on cyclin-dependent kinase (CDK) 4/6 inhibitor therapy (Sánchez-Bayona et al). At a median follow-up of 15 months, the estimated median progression-free survival (PFS) was 6.0 months (95% CI 5.3-7.8 months); PFS was longer among those with previous CDK4/6 inhibitor use lasting >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral disease (8.0 months; 95% CI 5.8-10.5 months), and those who were chemotherapy-naive in the advanced setting (7.2 months; 95% CI 5.9-8.4 months). These data support a role for everolimus plus ET as a treatment option post–CDK4/6 inhibitor treatment for selected patient populations, including those whose tumors lack targetable somatic mutations (such as PIK3CA and ESR1 mutations), and may provide meaningful clinical benefit in this setting.

Additional References

1. Rothwell PM, Wilson M, Price JF,  et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591-601. doi: 10.1016/S0140-6736(12)60209-8 Source
2. Okada S, Morimoto T, Ogawa H, et al, and the JPAD Trial Investigators. Effect of aspirin on cancer chemoprevention in Japanese patients with type 2 diabetes: 10-year observational follow-up of a randomized controlled trial. Diabetes Care. 2018;41:1757-1764. doi: 10.2337/dc18-0368 Source
3. Burn J, Sheth H, Elliott F, et al, on behalf of the CAPP2 Investigators. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: A double-blind, randomised, placebo-controlled trial. Lancet. 2020;395:1855-1863. doi: 10.1016/S0140-6736(20)30366-4 Source
4. Shao C, Yu Z, Xiao J, et al. Prognosis of pregnancy-associated breast cancer: A meta-analysis. BMC Cancer. 2020;20:746. doi: 10.1186/s12885-020-07248-8 Source
5. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402-2416. doi: 10.1001/jama.2017.7112 Source
6. Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37:496-513. doi: 10.1016/j.ccell.2020.03.009 Source
7. Kornblum N, Zhao F, Manola J, et al. Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: Results of PrE0102. J Clin Oncol. 2018;36:1556-1563. doi: 10.1200/JCO.2017.76.9331 Source

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

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

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

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

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

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

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source