Clinical Edge Journal Scan

Key clinical point: Patients with active psoriatic arthritis (PsA) who received ustekinumab for 160 weeks showed rapid and sustained improvements in the signs and symptoms of PsA.

Major finding: A decrease in both tender joint count (TJC; 8.0 to 5.8) and swollen joint count (SJC; 4.5 to 3.1) was observed from baseline to week 4, with further decrease until week 28. Improvements were sustained up to week 160 (TJC 1.0; SJC 0.4). Minimal disease activity was achieved by 31.9% of patients at week 28 and 33.6% of patients at week 52.

Study details: Findings are from the prospective, non-interventional SUSTAIN study including 129 patients with active PsA and a previous inadequate response to disease-modifying antirheumatic drugs who were followed up to week 160.

Disclosures: The SUSTAIN study was funded by Janssen-Cilag GmbH. Three authors declared being employees of Janssen-Cilag GmbH and holding stocks in Johnson and Johnson, the parent company of Janssen. The other authors declared no conflicts of interest.

Source: Wendler J et al. Ustekinumab is rapid-acting and is an effective long-term treatment for patients with active psoriatic arthritis: Real-world evidence from the non-interventional SUSTAIN study. Rheumatol Ther. 2022 (Sep 6). Doi: 10.1007/s40744-022-00484-3

Key clinical point: Patients with active psoriatic arthritis (PsA) who received ustekinumab for 160 weeks showed rapid and sustained improvements in the signs and symptoms of PsA.

Major finding: A decrease in both tender joint count (TJC; 8.0 to 5.8) and swollen joint count (SJC; 4.5 to 3.1) was observed from baseline to week 4, with further decrease until week 28. Improvements were sustained up to week 160 (TJC 1.0; SJC 0.4). Minimal disease activity was achieved by 31.9% of patients at week 28 and 33.6% of patients at week 52.

Study details: Findings are from the prospective, non-interventional SUSTAIN study including 129 patients with active PsA and a previous inadequate response to disease-modifying antirheumatic drugs who were followed up to week 160.

Disclosures: The SUSTAIN study was funded by Janssen-Cilag GmbH. Three authors declared being employees of Janssen-Cilag GmbH and holding stocks in Johnson and Johnson, the parent company of Janssen. The other authors declared no conflicts of interest.

Source: Wendler J et al. Ustekinumab is rapid-acting and is an effective long-term treatment for patients with active psoriatic arthritis: Real-world evidence from the non-interventional SUSTAIN study. Rheumatol Ther. 2022 (Sep 6). Doi: 10.1007/s40744-022-00484-3

Key clinical point: Patients with active psoriatic arthritis (PsA) who received ustekinumab for 160 weeks showed rapid and sustained improvements in the signs and symptoms of PsA.

Major finding: A decrease in both tender joint count (TJC; 8.0 to 5.8) and swollen joint count (SJC; 4.5 to 3.1) was observed from baseline to week 4, with further decrease until week 28. Improvements were sustained up to week 160 (TJC 1.0; SJC 0.4). Minimal disease activity was achieved by 31.9% of patients at week 28 and 33.6% of patients at week 52.

Study details: Findings are from the prospective, non-interventional SUSTAIN study including 129 patients with active PsA and a previous inadequate response to disease-modifying antirheumatic drugs who were followed up to week 160.

Disclosures: The SUSTAIN study was funded by Janssen-Cilag GmbH. Three authors declared being employees of Janssen-Cilag GmbH and holding stocks in Johnson and Johnson, the parent company of Janssen. The other authors declared no conflicts of interest.

Source: Wendler J et al. Ustekinumab is rapid-acting and is an effective long-term treatment for patients with active psoriatic arthritis: Real-world evidence from the non-interventional SUSTAIN study. Rheumatol Ther. 2022 (Sep 6). Doi: 10.1007/s40744-022-00484-3

Key clinical point: Patients with isolated axial psoriatic arthritis (PsA) had a better functional status than those with both axial and peripheral disease. Human leucocyte antigen (HLA)-B*27 positivity was associated with isolated axial PsA and predicted the development of peripheral disease over time.

Major finding: Compared with patients with concomitant axial and peripheral disease, HLA-B*27 positivity (odds ratio [OR] 25.00; P < .003) and lower Health Assessment Questionnaire scores (OR 0.004; P < .01) were associated with isolated axial disease. HLA-B*27 positivity predicted the development of peripheral PsA in patients with isolated axial PsA (hazard ratio 7.544; P < .006).

Study details: Findings are from a longitudinal study including 1688 patients with ankylosing spondylitis and psoriasis and 1576 patients with PsA, of which 32 had isolated axial disease and 463 had axial with peripheral disease.

Disclosures: The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Isolated axial disease in psoriatic arthritis and ankylosing spondylitis with psoriasis. Ann Rheum Dis. 2022 (Aug 16). Doi: 10.1136/ard-2022-222537

Key clinical point: Patients with isolated axial psoriatic arthritis (PsA) had a better functional status than those with both axial and peripheral disease. Human leucocyte antigen (HLA)-B*27 positivity was associated with isolated axial PsA and predicted the development of peripheral disease over time.

Major finding: Compared with patients with concomitant axial and peripheral disease, HLA-B*27 positivity (odds ratio [OR] 25.00; P < .003) and lower Health Assessment Questionnaire scores (OR 0.004; P < .01) were associated with isolated axial disease. HLA-B*27 positivity predicted the development of peripheral PsA in patients with isolated axial PsA (hazard ratio 7.544; P < .006).

Study details: Findings are from a longitudinal study including 1688 patients with ankylosing spondylitis and psoriasis and 1576 patients with PsA, of which 32 had isolated axial disease and 463 had axial with peripheral disease.

Disclosures: The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Isolated axial disease in psoriatic arthritis and ankylosing spondylitis with psoriasis. Ann Rheum Dis. 2022 (Aug 16). Doi: 10.1136/ard-2022-222537

Key clinical point: Patients with isolated axial psoriatic arthritis (PsA) had a better functional status than those with both axial and peripheral disease. Human leucocyte antigen (HLA)-B*27 positivity was associated with isolated axial PsA and predicted the development of peripheral disease over time.

Major finding: Compared with patients with concomitant axial and peripheral disease, HLA-B*27 positivity (odds ratio [OR] 25.00; P < .003) and lower Health Assessment Questionnaire scores (OR 0.004; P < .01) were associated with isolated axial disease. HLA-B*27 positivity predicted the development of peripheral PsA in patients with isolated axial PsA (hazard ratio 7.544; P < .006).

Study details: Findings are from a longitudinal study including 1688 patients with ankylosing spondylitis and psoriasis and 1576 patients with PsA, of which 32 had isolated axial disease and 463 had axial with peripheral disease.

Disclosures: The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Isolated axial disease in psoriatic arthritis and ankylosing spondylitis with psoriasis. Ann Rheum Dis. 2022 (Aug 16). Doi: 10.1136/ard-2022-222537

Key clinical point: Secukinumab significantly delayed disease flare compared with placebo and showed a consistent safety profile in patients with juvenile psoriatic arthritis (JPsA).

Major finding: Secukinumab vs placebo was associated with a significant delay in disease flare (hazard ratio 0.15; P < .001) and a higher proportion of patients achieving juvenile idiopathic arthritis American College of Rheumatology 30 response at week 104 (86.7% vs 62.5%). No new safety concerns were observed.

Study details: Findings are from a treatment-withdrawal, phase 3 study including 86 biologic-naive patients with active enthesitis-related arthritis (n = 52) or JPsA (n = 34) who were randomly assigned to receive secukinumab or placebo for up to 104 weeks.

Disclosures: This study was sponsored by Novartis Pharma AG. Four authors declared being employees and shareholders of Novartis. The other authors reported ties with several sources, including Novartis.

Source: Brunner HI et al on behalf of Paediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: A randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial. Ann Rheum Dis. 2022 (Aug 12). Doi: 10.1136/ard-2022-222849

Key clinical point: Secukinumab significantly delayed disease flare compared with placebo and showed a consistent safety profile in patients with juvenile psoriatic arthritis (JPsA).

Major finding: Secukinumab vs placebo was associated with a significant delay in disease flare (hazard ratio 0.15; P < .001) and a higher proportion of patients achieving juvenile idiopathic arthritis American College of Rheumatology 30 response at week 104 (86.7% vs 62.5%). No new safety concerns were observed.

Study details: Findings are from a treatment-withdrawal, phase 3 study including 86 biologic-naive patients with active enthesitis-related arthritis (n = 52) or JPsA (n = 34) who were randomly assigned to receive secukinumab or placebo for up to 104 weeks.

Disclosures: This study was sponsored by Novartis Pharma AG. Four authors declared being employees and shareholders of Novartis. The other authors reported ties with several sources, including Novartis.

Source: Brunner HI et al on behalf of Paediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: A randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial. Ann Rheum Dis. 2022 (Aug 12). Doi: 10.1136/ard-2022-222849

Key clinical point: Secukinumab significantly delayed disease flare compared with placebo and showed a consistent safety profile in patients with juvenile psoriatic arthritis (JPsA).

Major finding: Secukinumab vs placebo was associated with a significant delay in disease flare (hazard ratio 0.15; P < .001) and a higher proportion of patients achieving juvenile idiopathic arthritis American College of Rheumatology 30 response at week 104 (86.7% vs 62.5%). No new safety concerns were observed.

Study details: Findings are from a treatment-withdrawal, phase 3 study including 86 biologic-naive patients with active enthesitis-related arthritis (n = 52) or JPsA (n = 34) who were randomly assigned to receive secukinumab or placebo for up to 104 weeks.

Disclosures: This study was sponsored by Novartis Pharma AG. Four authors declared being employees and shareholders of Novartis. The other authors reported ties with several sources, including Novartis.

Source: Brunner HI et al on behalf of Paediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: A randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial. Ann Rheum Dis. 2022 (Aug 12). Doi: 10.1136/ard-2022-222849

The theme of this month's commentary is alternative outcomes measures for future migraine studies. The traditional outcomes measures, such as headache frequency measured in headache days, have long been considered gold standards when evaluating the efficacy of preventive interventions. When headache conditions are complicated by interictal pain or other symptoms, or when medication overuse adds a higher frequency or greater severity, those traditional measures are somewhat less exact and specific. Meaningful change for patients with higher frequency of attacks, near-continuous pain, or other migraine symptoms is quite different from that for those without these complications.

Ailani and colleagues reviewed post hoc data from the CONQUER trial, a prior study evaluating the safety and efficacy of galcanezumab vs placebo in patients who had previously not benefited from two to four categories of migraine preventive medication. This refractory population was initially noted to have 4.1 fewer headache days per month than patients taking placebo, but the authors now attempted to review these data with a focus on a different measure: total pain burden (TPB). They defined daily TPB as a single composite measure assessing the frequency, duration, and severity of migraine, calculated by multiplying the number of hours of migraine by the maximum daily migraine pain severity score. The monthly TPB was calculated by adding the daily pain burden over the entire month. The Migraine Disability Assessment questionnaire (MIDAS) and Migraine-Specific Quality of Life Questionnaire (MSQ) scores were also included to compare migraine-related disability and quality of life.

The patients who received galcanezumab were noted to have a significantly lower TPB, both in episodic and chronic migraine. Significantly greater reductions in monthly TPB relative to placebo were observed at each individual month as well. The change from baseline TPB was also noted to be significantly improved in the galcanezumab group compared with the placebo group. The reduction in TPB was noted even when migraine-day reductions were accounted for as part of a sensitivity analysis.

Preventive trials for migraine treatment focus primarily on migraine-day reduction, and for many patients with higher-frequency migraine, this measure does not adequately account for their disease-related disability. This unique way of looking at pain as part of a bigger picture is much more significant and meaningful for this patient population. Migraine frequency is still a very important outcomes measure, but it would be wise to add TBP or another measure that looks more globally at disease-related disability, especially when investigating preventive options in patients with chronic migraine.

When considering whether an intervention is helpful, most patients and clinicians follow the headache frequency, severity, or quality-of-life factors. As most patients will readily report, not all "headache-free days" are created equal. Although most people with migraine will experience days with absolutely no headache pain or other migraine-associated symptoms, on many days they will still have some symptoms of migraine. Lee and colleagues attempted to quantify the difference between headache-free days and crystal-clear days.

Most headache studies use the frequency of headache days as a primary or secondary outcome. This study collected data on both headache days and crystal-clear days, using data from a questionnaire-based large South Korean nationwide population study that evaluated headache and sleep. The study questions were validated for migraine and aura, and included: "How many days have you had a headache during the previous 30 days?" and "How many days have you had crystal-clear days without headache during the previous 30 days?" The data were then analyzed and compared with the widespread pain index (criteria for fibromyalgia) as well as sleep duration, sleep quality, depression and anxiety scales, and an allodynia checklist.

A little over 3000 respondents completed the surveys; 1938 had experienced headache over the past year, 170 were classified as having a diagnosis of migraine, and 50 of those were diagnosed with aura as well. Out of the patients with migraine, 97% had "unclear days." This was higher than the rate of those with non-migraine headaches (91%). Nearly all people surveyed had some crystal-clear days (99.4%).

The number of crystal-clear days per 30 days was significantly lower in participants with migraine than in those with non-migraine headache. Participants with migraine also had higher frequencies of cutaneous allodynia, anxiety, and depression. The weekly average sleep duration in participants with migraine did not significantly differ from that in participants with non-migraine headaches. The widespread pain index rate was much higher in those with migraine as well.

Most patients will definitely understand the difference between crystal-clear and unclear headache days. Many of the newer outcomes studies in migraine have started focusing on the most bothersome symptom, as headache pain is far from the only significant or disabling symptom associated with migraine. This study makes clear that further outcomes changes are necessary, and that a potentially more meaningful result in migraine studies may actually be crystal-clear days rather than simply headache-free days.

Although there are more acute options available for headache treatment, medication overuse headache remains a major complicating factor for most clinicians who treat headache. When educating patients, there is always a strong emphasis on guidelines for acute medication use. Many patients struggle with knowing when to use an acute treatment and when to alternate with a different treatment, and often they will withhold treatment completely due to fear of medication overuse. The new class of calcitonin gene-related peptide (CGRP) antagonist medications has shown some potential benefit as a preventive option for both medication overuse headache and migraine.

The prospective study by Curone and colleagues enrolled 300 patients with confirmed medication overuse headache who did not undergo withdrawal of the overused acute medication. Patients who are already taking preventive medications were excluded, as were patients with diagnoses other than chronic migraine or medication overuse. Patients were given one of the three injectable CGRP antagonist medications for prevention and were followed up at 3, 6, 9, and 12 months. The primary outcome was MIDAS score as well as monthly headache days and analgesic consumption.

Out of 303 patients, 242 (80%) showed both a ≥50% reduction of monthly headache days and ≥50% reduction in analgesic intake at 3-month follow-up visit. At 9 months, 198 (65%) were still responders. Monthly analgesic intake decreased ≥50% in 268 of 303 patients (88%) at 3 months and in 241 of 303 patients (79%) at the 6-month follow-up.

For years there has been a debate regarding whether withdrawal of an overused medication is necessary for effective treatment of medication overuse headache. Many preventive treatments are less effective when medication overuse is ongoing. The CGRP class of medications does appear to be effective even with ongoing acute medication overuse. This class of medications should definitely be considered when withdrawing an overused medication is complicated, or when a patient needs to continue to take analgesic medications for another condition.

The theme of this month's commentary is alternative outcomes measures for future migraine studies. The traditional outcomes measures, such as headache frequency measured in headache days, have long been considered gold standards when evaluating the efficacy of preventive interventions. When headache conditions are complicated by interictal pain or other symptoms, or when medication overuse adds a higher frequency or greater severity, those traditional measures are somewhat less exact and specific. Meaningful change for patients with higher frequency of attacks, near-continuous pain, or other migraine symptoms is quite different from that for those without these complications.

Ailani and colleagues reviewed post hoc data from the CONQUER trial, a prior study evaluating the safety and efficacy of galcanezumab vs placebo in patients who had previously not benefited from two to four categories of migraine preventive medication. This refractory population was initially noted to have 4.1 fewer headache days per month than patients taking placebo, but the authors now attempted to review these data with a focus on a different measure: total pain burden (TPB). They defined daily TPB as a single composite measure assessing the frequency, duration, and severity of migraine, calculated by multiplying the number of hours of migraine by the maximum daily migraine pain severity score. The monthly TPB was calculated by adding the daily pain burden over the entire month. The Migraine Disability Assessment questionnaire (MIDAS) and Migraine-Specific Quality of Life Questionnaire (MSQ) scores were also included to compare migraine-related disability and quality of life.

The patients who received galcanezumab were noted to have a significantly lower TPB, both in episodic and chronic migraine. Significantly greater reductions in monthly TPB relative to placebo were observed at each individual month as well. The change from baseline TPB was also noted to be significantly improved in the galcanezumab group compared with the placebo group. The reduction in TPB was noted even when migraine-day reductions were accounted for as part of a sensitivity analysis.

Preventive trials for migraine treatment focus primarily on migraine-day reduction, and for many patients with higher-frequency migraine, this measure does not adequately account for their disease-related disability. This unique way of looking at pain as part of a bigger picture is much more significant and meaningful for this patient population. Migraine frequency is still a very important outcomes measure, but it would be wise to add TBP or another measure that looks more globally at disease-related disability, especially when investigating preventive options in patients with chronic migraine.

When considering whether an intervention is helpful, most patients and clinicians follow the headache frequency, severity, or quality-of-life factors. As most patients will readily report, not all "headache-free days" are created equal. Although most people with migraine will experience days with absolutely no headache pain or other migraine-associated symptoms, on many days they will still have some symptoms of migraine. Lee and colleagues attempted to quantify the difference between headache-free days and crystal-clear days.

Most headache studies use the frequency of headache days as a primary or secondary outcome. This study collected data on both headache days and crystal-clear days, using data from a questionnaire-based large South Korean nationwide population study that evaluated headache and sleep. The study questions were validated for migraine and aura, and included: "How many days have you had a headache during the previous 30 days?" and "How many days have you had crystal-clear days without headache during the previous 30 days?" The data were then analyzed and compared with the widespread pain index (criteria for fibromyalgia) as well as sleep duration, sleep quality, depression and anxiety scales, and an allodynia checklist.

A little over 3000 respondents completed the surveys; 1938 had experienced headache over the past year, 170 were classified as having a diagnosis of migraine, and 50 of those were diagnosed with aura as well. Out of the patients with migraine, 97% had "unclear days." This was higher than the rate of those with non-migraine headaches (91%). Nearly all people surveyed had some crystal-clear days (99.4%).

The number of crystal-clear days per 30 days was significantly lower in participants with migraine than in those with non-migraine headache. Participants with migraine also had higher frequencies of cutaneous allodynia, anxiety, and depression. The weekly average sleep duration in participants with migraine did not significantly differ from that in participants with non-migraine headaches. The widespread pain index rate was much higher in those with migraine as well.

Most patients will definitely understand the difference between crystal-clear and unclear headache days. Many of the newer outcomes studies in migraine have started focusing on the most bothersome symptom, as headache pain is far from the only significant or disabling symptom associated with migraine. This study makes clear that further outcomes changes are necessary, and that a potentially more meaningful result in migraine studies may actually be crystal-clear days rather than simply headache-free days.

Although there are more acute options available for headache treatment, medication overuse headache remains a major complicating factor for most clinicians who treat headache. When educating patients, there is always a strong emphasis on guidelines for acute medication use. Many patients struggle with knowing when to use an acute treatment and when to alternate with a different treatment, and often they will withhold treatment completely due to fear of medication overuse. The new class of calcitonin gene-related peptide (CGRP) antagonist medications has shown some potential benefit as a preventive option for both medication overuse headache and migraine.

The prospective study by Curone and colleagues enrolled 300 patients with confirmed medication overuse headache who did not undergo withdrawal of the overused acute medication. Patients who are already taking preventive medications were excluded, as were patients with diagnoses other than chronic migraine or medication overuse. Patients were given one of the three injectable CGRP antagonist medications for prevention and were followed up at 3, 6, 9, and 12 months. The primary outcome was MIDAS score as well as monthly headache days and analgesic consumption.

Out of 303 patients, 242 (80%) showed both a ≥50% reduction of monthly headache days and ≥50% reduction in analgesic intake at 3-month follow-up visit. At 9 months, 198 (65%) were still responders. Monthly analgesic intake decreased ≥50% in 268 of 303 patients (88%) at 3 months and in 241 of 303 patients (79%) at the 6-month follow-up.

For years there has been a debate regarding whether withdrawal of an overused medication is necessary for effective treatment of medication overuse headache. Many preventive treatments are less effective when medication overuse is ongoing. The CGRP class of medications does appear to be effective even with ongoing acute medication overuse. This class of medications should definitely be considered when withdrawing an overused medication is complicated, or when a patient needs to continue to take analgesic medications for another condition.

The theme of this month's commentary is alternative outcomes measures for future migraine studies. The traditional outcomes measures, such as headache frequency measured in headache days, have long been considered gold standards when evaluating the efficacy of preventive interventions. When headache conditions are complicated by interictal pain or other symptoms, or when medication overuse adds a higher frequency or greater severity, those traditional measures are somewhat less exact and specific. Meaningful change for patients with higher frequency of attacks, near-continuous pain, or other migraine symptoms is quite different from that for those without these complications.

Ailani and colleagues reviewed post hoc data from the CONQUER trial, a prior study evaluating the safety and efficacy of galcanezumab vs placebo in patients who had previously not benefited from two to four categories of migraine preventive medication. This refractory population was initially noted to have 4.1 fewer headache days per month than patients taking placebo, but the authors now attempted to review these data with a focus on a different measure: total pain burden (TPB). They defined daily TPB as a single composite measure assessing the frequency, duration, and severity of migraine, calculated by multiplying the number of hours of migraine by the maximum daily migraine pain severity score. The monthly TPB was calculated by adding the daily pain burden over the entire month. The Migraine Disability Assessment questionnaire (MIDAS) and Migraine-Specific Quality of Life Questionnaire (MSQ) scores were also included to compare migraine-related disability and quality of life.

The patients who received galcanezumab were noted to have a significantly lower TPB, both in episodic and chronic migraine. Significantly greater reductions in monthly TPB relative to placebo were observed at each individual month as well. The change from baseline TPB was also noted to be significantly improved in the galcanezumab group compared with the placebo group. The reduction in TPB was noted even when migraine-day reductions were accounted for as part of a sensitivity analysis.

Preventive trials for migraine treatment focus primarily on migraine-day reduction, and for many patients with higher-frequency migraine, this measure does not adequately account for their disease-related disability. This unique way of looking at pain as part of a bigger picture is much more significant and meaningful for this patient population. Migraine frequency is still a very important outcomes measure, but it would be wise to add TBP or another measure that looks more globally at disease-related disability, especially when investigating preventive options in patients with chronic migraine.

When considering whether an intervention is helpful, most patients and clinicians follow the headache frequency, severity, or quality-of-life factors. As most patients will readily report, not all "headache-free days" are created equal. Although most people with migraine will experience days with absolutely no headache pain or other migraine-associated symptoms, on many days they will still have some symptoms of migraine. Lee and colleagues attempted to quantify the difference between headache-free days and crystal-clear days.

Most headache studies use the frequency of headache days as a primary or secondary outcome. This study collected data on both headache days and crystal-clear days, using data from a questionnaire-based large South Korean nationwide population study that evaluated headache and sleep. The study questions were validated for migraine and aura, and included: "How many days have you had a headache during the previous 30 days?" and "How many days have you had crystal-clear days without headache during the previous 30 days?" The data were then analyzed and compared with the widespread pain index (criteria for fibromyalgia) as well as sleep duration, sleep quality, depression and anxiety scales, and an allodynia checklist.

A little over 3000 respondents completed the surveys; 1938 had experienced headache over the past year, 170 were classified as having a diagnosis of migraine, and 50 of those were diagnosed with aura as well. Out of the patients with migraine, 97% had "unclear days." This was higher than the rate of those with non-migraine headaches (91%). Nearly all people surveyed had some crystal-clear days (99.4%).

The number of crystal-clear days per 30 days was significantly lower in participants with migraine than in those with non-migraine headache. Participants with migraine also had higher frequencies of cutaneous allodynia, anxiety, and depression. The weekly average sleep duration in participants with migraine did not significantly differ from that in participants with non-migraine headaches. The widespread pain index rate was much higher in those with migraine as well.

Most patients will definitely understand the difference between crystal-clear and unclear headache days. Many of the newer outcomes studies in migraine have started focusing on the most bothersome symptom, as headache pain is far from the only significant or disabling symptom associated with migraine. This study makes clear that further outcomes changes are necessary, and that a potentially more meaningful result in migraine studies may actually be crystal-clear days rather than simply headache-free days.

Although there are more acute options available for headache treatment, medication overuse headache remains a major complicating factor for most clinicians who treat headache. When educating patients, there is always a strong emphasis on guidelines for acute medication use. Many patients struggle with knowing when to use an acute treatment and when to alternate with a different treatment, and often they will withhold treatment completely due to fear of medication overuse. The new class of calcitonin gene-related peptide (CGRP) antagonist medications has shown some potential benefit as a preventive option for both medication overuse headache and migraine.

The prospective study by Curone and colleagues enrolled 300 patients with confirmed medication overuse headache who did not undergo withdrawal of the overused acute medication. Patients who are already taking preventive medications were excluded, as were patients with diagnoses other than chronic migraine or medication overuse. Patients were given one of the three injectable CGRP antagonist medications for prevention and were followed up at 3, 6, 9, and 12 months. The primary outcome was MIDAS score as well as monthly headache days and analgesic consumption.

Out of 303 patients, 242 (80%) showed both a ≥50% reduction of monthly headache days and ≥50% reduction in analgesic intake at 3-month follow-up visit. At 9 months, 198 (65%) were still responders. Monthly analgesic intake decreased ≥50% in 268 of 303 patients (88%) at 3 months and in 241 of 303 patients (79%) at the 6-month follow-up.

For years there has been a debate regarding whether withdrawal of an overused medication is necessary for effective treatment of medication overuse headache. Many preventive treatments are less effective when medication overuse is ongoing. The CGRP class of medications does appear to be effective even with ongoing acute medication overuse. This class of medications should definitely be considered when withdrawing an overused medication is complicated, or when a patient needs to continue to take analgesic medications for another condition.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

In the PD-L1 CPS ≥ 1 subgroup, however, no significant OS benefit was observed (median OS 17.6 months vs 16.0 months; HR 0.86; 95% CI 0.72-1.04; P = .1125). Additionally, in an exploratory analysis, the addition of pembrolizumab showed consistent OS benefit among patients whose tumors express PD-L1 with a CPS of 10-19 and CPS ≥ 20. The updated progression-free survival (PFS) and objective response rates (ORR) were consistent with prior interim data. No new safety signals were observed after the longer follow-up.

These data confirm that pembrolizumab plus chemotherapy should remain the first-line treatment for patients with advanced or metastatic TNBC whose tumors express PD-L1 with a CPS of ≥ 10. The treatment of metastatic TNBC with low or negative PD-L1 CPS scores remains an area of unmet clinical need, and further research is needed to explore better options for these patients.

Wang and colleagues presented results from a randomized, phase 3 trial comparing first-line nab-paclitaxel plus cisplatin (AP) with gemcitabine plus cisplatin (GP) among 254 patients with previously untreated metastatic TNBC. Median PFS (mPFS) was 9.8 months with AP vs 7.4 months with GP (HR 0.67; 95% CI 0.50-0.88; P  =  .004). Furthermore, AP had significantly higher ORR compared with GP (81.1% vs 56.3%; P  <  .001) and significantly improved median OS (26.3 months vs 22.9 months; HR 0.62; 95% CI 0.44-0.90; P  =  .010).

In the exploratory analyses of PFS by stratification factors, the mPFS was significantly longer in the AP group compared with the GP group in the majority of subgroups, except for those patients who presented with de novo stage IV disease or a disease-free interval of < 1 year. Regarding safety data, a significantly higher incidence of grade ≥ 3 neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) was noted in the AP group compared with the GP group, while grade ≥ 3 thrombocytopenia was more common in the GP group compared with the AP group (29.4% vs 3.9%).

The AP doublet achieved superior efficacy with a manageable safety profile, compared with GP in patients with previously untreated metastatic TNBC. It is not clear, however, whether the AP doublet is superior to single-agent therapy in this setting, especially given several prior studies that showed no survival benefit and increased toxicity from combination therapy compared with sequential single-agent therapy in metastatic breast cancer. More studies are needed to establish the role of the AP doublet in combination with pembrolizumab in this cohort of patients, given that first-line pembrolizumab plus chemotherapy is considered the standard of care for patients with metastatic TNBC whose tumors express PD-L1.

Rugo and colleagues presented results from a randomized phase 3 study comparing 205 mg/m² oral paclitaxel plus 15 mg encequidar (a novel P-glycoprotein pump inhibitor that allows oral absorption of paclitaxel) on 3 consecutive days per week vs 175 mg/m² intravenous paclitaxel once every 3 weeks. The study enrolled 402 postmenopausal women from Latin America with metastatic breast cancer who were at least 1 year from their last taxane therapy. Oral paclitaxel plus encequidar (oPac + E) increased the confirmed tumor response compared with intravenous paclitaxel (IVpac) (36% vs 23%; P = .01). There was a trend toward improved PFS (8.4 vs 7.4 months; HR 0.768; 95.5% CI 0.584-1.01; P = .046) and OS (22.7 vs 16.5 months; HR 0.794; 95.5% CI 0.607-1.037; P = .08) with oPac + E compared to IVpac, respectively. Grade ≥3 adverse events were comparable with oPac + E and IVpac (55% vs 53%), although a lower incidence of grade 3 neuropathy (2% vs 15%) and alopecia (49% vs 62%) was noted with oPac + E compared with IVpac. A higher incidence of grade ≥ 3 gastrointestinal toxicity (nausea, vomiting, and diarrhea) and grade 4 neutropenic complications was noted in the oPac + E group. Patients with elevated baseline liver enzymes were particularly susceptible to early neutropenia and serious infections.

This study demonstrates that oral paclitaxel can be a possible alternative treatment option to intravenous paclitaxel in a select group of patients with metastatic breast cancer. High-grade neutropenia appears to be a major treatment-limiting toxicity with oPac + E. Therefore, careful patient selection and close monitoring are crucial for the successful management of this adverse event.

In the PD-L1 CPS ≥ 1 subgroup, however, no significant OS benefit was observed (median OS 17.6 months vs 16.0 months; HR 0.86; 95% CI 0.72-1.04; P = .1125). Additionally, in an exploratory analysis, the addition of pembrolizumab showed consistent OS benefit among patients whose tumors express PD-L1 with a CPS of 10-19 and CPS ≥ 20. The updated progression-free survival (PFS) and objective response rates (ORR) were consistent with prior interim data. No new safety signals were observed after the longer follow-up.

These data confirm that pembrolizumab plus chemotherapy should remain the first-line treatment for patients with advanced or metastatic TNBC whose tumors express PD-L1 with a CPS of ≥ 10. The treatment of metastatic TNBC with low or negative PD-L1 CPS scores remains an area of unmet clinical need, and further research is needed to explore better options for these patients.

Wang and colleagues presented results from a randomized, phase 3 trial comparing first-line nab-paclitaxel plus cisplatin (AP) with gemcitabine plus cisplatin (GP) among 254 patients with previously untreated metastatic TNBC. Median PFS (mPFS) was 9.8 months with AP vs 7.4 months with GP (HR 0.67; 95% CI 0.50-0.88; P  =  .004). Furthermore, AP had significantly higher ORR compared with GP (81.1% vs 56.3%; P  <  .001) and significantly improved median OS (26.3 months vs 22.9 months; HR 0.62; 95% CI 0.44-0.90; P  =  .010).

In the exploratory analyses of PFS by stratification factors, the mPFS was significantly longer in the AP group compared with the GP group in the majority of subgroups, except for those patients who presented with de novo stage IV disease or a disease-free interval of < 1 year. Regarding safety data, a significantly higher incidence of grade ≥ 3 neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) was noted in the AP group compared with the GP group, while grade ≥ 3 thrombocytopenia was more common in the GP group compared with the AP group (29.4% vs 3.9%).

The AP doublet achieved superior efficacy with a manageable safety profile, compared with GP in patients with previously untreated metastatic TNBC. It is not clear, however, whether the AP doublet is superior to single-agent therapy in this setting, especially given several prior studies that showed no survival benefit and increased toxicity from combination therapy compared with sequential single-agent therapy in metastatic breast cancer. More studies are needed to establish the role of the AP doublet in combination with pembrolizumab in this cohort of patients, given that first-line pembrolizumab plus chemotherapy is considered the standard of care for patients with metastatic TNBC whose tumors express PD-L1.

Rugo and colleagues presented results from a randomized phase 3 study comparing 205 mg/m² oral paclitaxel plus 15 mg encequidar (a novel P-glycoprotein pump inhibitor that allows oral absorption of paclitaxel) on 3 consecutive days per week vs 175 mg/m² intravenous paclitaxel once every 3 weeks. The study enrolled 402 postmenopausal women from Latin America with metastatic breast cancer who were at least 1 year from their last taxane therapy. Oral paclitaxel plus encequidar (oPac + E) increased the confirmed tumor response compared with intravenous paclitaxel (IVpac) (36% vs 23%; P = .01). There was a trend toward improved PFS (8.4 vs 7.4 months; HR 0.768; 95.5% CI 0.584-1.01; P = .046) and OS (22.7 vs 16.5 months; HR 0.794; 95.5% CI 0.607-1.037; P = .08) with oPac + E compared to IVpac, respectively. Grade ≥3 adverse events were comparable with oPac + E and IVpac (55% vs 53%), although a lower incidence of grade 3 neuropathy (2% vs 15%) and alopecia (49% vs 62%) was noted with oPac + E compared with IVpac. A higher incidence of grade ≥ 3 gastrointestinal toxicity (nausea, vomiting, and diarrhea) and grade 4 neutropenic complications was noted in the oPac + E group. Patients with elevated baseline liver enzymes were particularly susceptible to early neutropenia and serious infections.

This study demonstrates that oral paclitaxel can be a possible alternative treatment option to intravenous paclitaxel in a select group of patients with metastatic breast cancer. High-grade neutropenia appears to be a major treatment-limiting toxicity with oPac + E. Therefore, careful patient selection and close monitoring are crucial for the successful management of this adverse event.

In the PD-L1 CPS ≥ 1 subgroup, however, no significant OS benefit was observed (median OS 17.6 months vs 16.0 months; HR 0.86; 95% CI 0.72-1.04; P = .1125). Additionally, in an exploratory analysis, the addition of pembrolizumab showed consistent OS benefit among patients whose tumors express PD-L1 with a CPS of 10-19 and CPS ≥ 20. The updated progression-free survival (PFS) and objective response rates (ORR) were consistent with prior interim data. No new safety signals were observed after the longer follow-up.

These data confirm that pembrolizumab plus chemotherapy should remain the first-line treatment for patients with advanced or metastatic TNBC whose tumors express PD-L1 with a CPS of ≥ 10. The treatment of metastatic TNBC with low or negative PD-L1 CPS scores remains an area of unmet clinical need, and further research is needed to explore better options for these patients.

Wang and colleagues presented results from a randomized, phase 3 trial comparing first-line nab-paclitaxel plus cisplatin (AP) with gemcitabine plus cisplatin (GP) among 254 patients with previously untreated metastatic TNBC. Median PFS (mPFS) was 9.8 months with AP vs 7.4 months with GP (HR 0.67; 95% CI 0.50-0.88; P  =  .004). Furthermore, AP had significantly higher ORR compared with GP (81.1% vs 56.3%; P  <  .001) and significantly improved median OS (26.3 months vs 22.9 months; HR 0.62; 95% CI 0.44-0.90; P  =  .010).

In the exploratory analyses of PFS by stratification factors, the mPFS was significantly longer in the AP group compared with the GP group in the majority of subgroups, except for those patients who presented with de novo stage IV disease or a disease-free interval of < 1 year. Regarding safety data, a significantly higher incidence of grade ≥ 3 neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) was noted in the AP group compared with the GP group, while grade ≥ 3 thrombocytopenia was more common in the GP group compared with the AP group (29.4% vs 3.9%).

The AP doublet achieved superior efficacy with a manageable safety profile, compared with GP in patients with previously untreated metastatic TNBC. It is not clear, however, whether the AP doublet is superior to single-agent therapy in this setting, especially given several prior studies that showed no survival benefit and increased toxicity from combination therapy compared with sequential single-agent therapy in metastatic breast cancer. More studies are needed to establish the role of the AP doublet in combination with pembrolizumab in this cohort of patients, given that first-line pembrolizumab plus chemotherapy is considered the standard of care for patients with metastatic TNBC whose tumors express PD-L1.

Rugo and colleagues presented results from a randomized phase 3 study comparing 205 mg/m² oral paclitaxel plus 15 mg encequidar (a novel P-glycoprotein pump inhibitor that allows oral absorption of paclitaxel) on 3 consecutive days per week vs 175 mg/m² intravenous paclitaxel once every 3 weeks. The study enrolled 402 postmenopausal women from Latin America with metastatic breast cancer who were at least 1 year from their last taxane therapy. Oral paclitaxel plus encequidar (oPac + E) increased the confirmed tumor response compared with intravenous paclitaxel (IVpac) (36% vs 23%; P = .01). There was a trend toward improved PFS (8.4 vs 7.4 months; HR 0.768; 95.5% CI 0.584-1.01; P = .046) and OS (22.7 vs 16.5 months; HR 0.794; 95.5% CI 0.607-1.037; P = .08) with oPac + E compared to IVpac, respectively. Grade ≥3 adverse events were comparable with oPac + E and IVpac (55% vs 53%), although a lower incidence of grade 3 neuropathy (2% vs 15%) and alopecia (49% vs 62%) was noted with oPac + E compared with IVpac. A higher incidence of grade ≥ 3 gastrointestinal toxicity (nausea, vomiting, and diarrhea) and grade 4 neutropenic complications was noted in the oPac + E group. Patients with elevated baseline liver enzymes were particularly susceptible to early neutropenia and serious infections.

This study demonstrates that oral paclitaxel can be a possible alternative treatment option to intravenous paclitaxel in a select group of patients with metastatic breast cancer. High-grade neutropenia appears to be a major treatment-limiting toxicity with oPac + E. Therefore, careful patient selection and close monitoring are crucial for the successful management of this adverse event.

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739