Clinical Edge Journal Scan Commentary

Smoking is another important modifiable environmental factor. Smoking generally has an adverse impact on treatment. In a post hoc analysis of pooled data from phase 2 and 3 trials and a long-term extension study involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (a Janus kinase inhibitor) or placebo, Ogdie and coworkers assessed the impact of smoking on treatment efficacy and safety. The efficacy rates were generally similar in current/past smokers and never-smokers. The incidence rates of treatment-emergent adverse events were higher in current/past smokers compared with never-smokers. Thus, in contrast to tumor necrosis factor inhibitors, smoking status may not have an impact on tofacitinib efficacy. However, current/past smokers experienced increased rates of adverse events.

Secukinumab, an anti-interleukin (IL)-17A antibody, is an established treatment for PsA and is approved for use as fixed-dose (150/300 mg) subcutaneous injections. The efficacy and safety of weight-based intravenous (IV) therapy is unknown. Kivitz and colleagues recently reported the results of the phase 3 INVIGORATE-2 trial, in which 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive IV secukinumab or placebo with crossover to IV secukinumab at week 16. They demonstrated that at week 16, IV secukinumab significantly improved the American College of Rheumatology 50 response rate (ACR50) compared with placebo (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 and were sustained through week 52. No new safety signals were reported. Thus, IV secukinumab is a safe and efficacious treatment for PsA. This mode of administration of secukinumab is a welcome addition to the PsA therapeutic armamentarium.

There are many targeted therapies available for PsA. However, data on comparative effectiveness is lacking. Kristensen and associates reported the results of an interim analysis of the PRO-SPIRIT real-world study that included 1192 patients with PsA across six countries who initiated or switched to a new biologic or targeted synthetic disease-modifying antirheumatic drug. They showed that at 3 months, ixekizumab significantly improved clinical disease activity in patients with PsA compared with IL-12/23 inhibitors and IL-23 inhibitors. The improvements in the joints were similar to those with TNF inhibitors and JAK inhibitors, but the improvement in psoriasis was higher. Thus, ixekizumab leads to rapid response to active skin and musculoskeletal disease activity in PsA. Comparative data on treatment persistence as well as adverse events are required.

Smoking is another important modifiable environmental factor. Smoking generally has an adverse impact on treatment. In a post hoc analysis of pooled data from phase 2 and 3 trials and a long-term extension study involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (a Janus kinase inhibitor) or placebo, Ogdie and coworkers assessed the impact of smoking on treatment efficacy and safety. The efficacy rates were generally similar in current/past smokers and never-smokers. The incidence rates of treatment-emergent adverse events were higher in current/past smokers compared with never-smokers. Thus, in contrast to tumor necrosis factor inhibitors, smoking status may not have an impact on tofacitinib efficacy. However, current/past smokers experienced increased rates of adverse events.

Secukinumab, an anti-interleukin (IL)-17A antibody, is an established treatment for PsA and is approved for use as fixed-dose (150/300 mg) subcutaneous injections. The efficacy and safety of weight-based intravenous (IV) therapy is unknown. Kivitz and colleagues recently reported the results of the phase 3 INVIGORATE-2 trial, in which 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive IV secukinumab or placebo with crossover to IV secukinumab at week 16. They demonstrated that at week 16, IV secukinumab significantly improved the American College of Rheumatology 50 response rate (ACR50) compared with placebo (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 and were sustained through week 52. No new safety signals were reported. Thus, IV secukinumab is a safe and efficacious treatment for PsA. This mode of administration of secukinumab is a welcome addition to the PsA therapeutic armamentarium.

There are many targeted therapies available for PsA. However, data on comparative effectiveness is lacking. Kristensen and associates reported the results of an interim analysis of the PRO-SPIRIT real-world study that included 1192 patients with PsA across six countries who initiated or switched to a new biologic or targeted synthetic disease-modifying antirheumatic drug. They showed that at 3 months, ixekizumab significantly improved clinical disease activity in patients with PsA compared with IL-12/23 inhibitors and IL-23 inhibitors. The improvements in the joints were similar to those with TNF inhibitors and JAK inhibitors, but the improvement in psoriasis was higher. Thus, ixekizumab leads to rapid response to active skin and musculoskeletal disease activity in PsA. Comparative data on treatment persistence as well as adverse events are required.

Smoking is another important modifiable environmental factor. Smoking generally has an adverse impact on treatment. In a post hoc analysis of pooled data from phase 2 and 3 trials and a long-term extension study involving 914 patients with PsA and 372 patients with ankylosing spondylitis who received tofacitinib (a Janus kinase inhibitor) or placebo, Ogdie and coworkers assessed the impact of smoking on treatment efficacy and safety. The efficacy rates were generally similar in current/past smokers and never-smokers. The incidence rates of treatment-emergent adverse events were higher in current/past smokers compared with never-smokers. Thus, in contrast to tumor necrosis factor inhibitors, smoking status may not have an impact on tofacitinib efficacy. However, current/past smokers experienced increased rates of adverse events.

Secukinumab, an anti-interleukin (IL)-17A antibody, is an established treatment for PsA and is approved for use as fixed-dose (150/300 mg) subcutaneous injections. The efficacy and safety of weight-based intravenous (IV) therapy is unknown. Kivitz and colleagues recently reported the results of the phase 3 INVIGORATE-2 trial, in which 381 patients with active PsA and either plaque psoriasis or nail psoriasis were randomly assigned to receive IV secukinumab or placebo with crossover to IV secukinumab at week 16. They demonstrated that at week 16, IV secukinumab significantly improved the American College of Rheumatology 50 response rate (ACR50) compared with placebo (31.4% vs 6.3%; adjusted P < .0001). Improvements were observed as early as week 4 and were sustained through week 52. No new safety signals were reported. Thus, IV secukinumab is a safe and efficacious treatment for PsA. This mode of administration of secukinumab is a welcome addition to the PsA therapeutic armamentarium.

There are many targeted therapies available for PsA. However, data on comparative effectiveness is lacking. Kristensen and associates reported the results of an interim analysis of the PRO-SPIRIT real-world study that included 1192 patients with PsA across six countries who initiated or switched to a new biologic or targeted synthetic disease-modifying antirheumatic drug. They showed that at 3 months, ixekizumab significantly improved clinical disease activity in patients with PsA compared with IL-12/23 inhibitors and IL-23 inhibitors. The improvements in the joints were similar to those with TNF inhibitors and JAK inhibitors, but the improvement in psoriasis was higher. Thus, ixekizumab leads to rapid response to active skin and musculoskeletal disease activity in PsA. Comparative data on treatment persistence as well as adverse events are required.

Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors  who received bimekizumab (n = 698) or risankizumab (n = 589).¹
 

At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.

In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.² In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.

Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.³ This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.

PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).⁴ At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.

References

1. Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
2. Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
3. Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
4. Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source

Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors  who received bimekizumab (n = 698) or risankizumab (n = 589).¹
 

At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.

In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.² In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.

Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.³ This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.

PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).⁴ At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.

References

1. Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
2. Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
3. Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
4. Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source

Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors  who received bimekizumab (n = 698) or risankizumab (n = 589).¹
 

At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.

In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.² In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.

Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.³ This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.

PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).⁴ At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.

References

1. Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
2. Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
3. Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
4. Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.

Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.

Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.

Additional References

1. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
2. Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source

Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.

Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.

Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.

Additional References

1. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
2. Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source

Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.

Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.

Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.

Additional References

1. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
2. Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

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.

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

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.

Traidl and colleagues report that obesity was linked to worse AD in German patients. The authors hit the nail on the head with their conclusions: "In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance." What might account for the small difference in disease severity? Adherence to treatment is highly variable among patients with AD. A small tendency toward worse adherence in patients with obesity could easily explain the small differences seen in disease severity.

Eichenfeld and colleagues report that topical ruxolitinib maintained good efficacy over a year in open-label use. Topical ruxolitinib is a very effective treatment for AD. If real-life AD patients on topical ruxolitinib were to lose efficacy over time, I'd consider the possibility that they've developed mutant Janus kinase (JAK) enzymes that are no longer responsive to the drug. Just kidding. I doubt that such mutations ever occur. If topical ruxolitinib in AD patients were to lose efficacy over time, I'd strongly consider the possibility that patients' adherence to the treatment is no longer as good as it was before. Long-term adherence to topical treatment can be abysmal. Adherence in clinical trials is probably a lot better than in clinical practice. When we see topical treatments that are effective in clinical trials failing in real-life patients with AD, it may be prudent to address the possibility of poor adherence.

I'd love to see a head-to-head trial of tralokinumab vs dupilumab in the treatment of moderate to severe AD. Lacking that, Torres and colleagues report an indirect comparison of the two drugs in patients also treated with topical steroids. This study, funded by the manufacturer of tralokinumab, reported that the two drugs have similar efficacy. How much of the efficacy was due to the topical steroid use is not clear to me. I'd still love to see a head-to-head trial of tralokinumab vs dupilumab to have a better, more confident sense of their relative efficacy.

Is AD associated with brain cancer, as reported by Xin and colleagues? I'm not an expert in their methodology, but they did find a statistically significant increased risk, with an odds ratio of 1.0005. I understand the odds ratio for smoking and lung cancer to be about 80. Even if the increased odds of 1.005 — no, wait, that's 1.0005 — is truly due to AD, this tiny difference doesn't seem meaningful in any way.