Clinical Edge Journal Scan

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

I was excited to see that the study included the use of objective electronic monitoring of sleep quality. This was done using wrist actigraphy, devices on the wrist that measure acceleration movements. What a great tool this could be for measuring how much scratching our patients are doing! With devices like these measuring movements objectively, we wouldn't have to rely on patients' self-report of itch or sleep quality. Sadly, these monitors did not show any meaningful differences between the dupilumab and placebo groups. This technology holds great promise but it isn't yet ready for prime-time assessment of scratching or sleep.

The title of Chiesa Fuxench and colleagues' article, "Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis," might be scary to our patients. The authors reported that "children and adults with AD had an increased risk of IBD [inflammatory bowel disease]." The authors concluded, "Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms." Bah, humbug, I say!

Be careful when someone tells you there is increased risk. This study was done exceptionally well by an exceptionally good research team. They were working with a huge database and included many controls to ensure that their findings weren't due to chance. And while they did find an "increased risk," they proved — rather conclusively, I believe — that the increased risk is tiny and not something we need to worry about.

The results of this study suggest that there is a scientific link between AD and IBD, probably some genetic inflammatory signaling contributing to both conditions. But even in the highest-risk group, it would take seeing well over 1000 patients for a year to see one more case of IBD due to AD. This article is a good foundation for researchers who want to explore the underlying connection between AD and IBD. The study is an even better foundation for physicians who want to reassure patients that there is little to no meaningful increased risk for IBD in patients with AD.

Am I allowed to just say "Ditto!"? Wan and colleagues' article "Incidence of Cardiovascular Disease and Venous Thromboembolism in Patients with Atopic Dermatitis" does show a statistically significant increased risk for cardiovascular (CV) disease in patients with AD. Is that increase clinically significant? This study was also exceptionally well done by an exceptionally good research team. They concluded, "Atopic dermatitis, particularly when severe, is associated with increased risks of venous thromboembolism and CV disease, which may influence the monitoring of patients and selection of treatments for AD." I look at their findings and conclude that AD, even when severe, is associated with little if any clinically meaningful increased risks for venous thromboembolism or CV disease, and we don't need to add any special CV monitoring of AD patients.

The key data are presented in Table 2 of their manuscript. In children, the risk for deep vein thrombosis (DVT) in those with severe AD was about 3 times (0.16) that of those with no AD (0.05). But those numbers are per 1000 patient-years. Therefore, the increased risk is 0.16 - 0.05 = 0.11/1000 patient-years. Thus, you'd expect to see one more case of DVT per year in every 9000 children with severe AD. Does that mean we need to monitor all 9000 for DVT? Would that be cost-effective? Might the monitoring cause more problems than it would solve?

CV disease is much more common in adults than in children, but still, with a difference in risk of about 0.5-1 per 1000 patient-years, you'd only expect one more event due to AD in every 1000-2000 patients, and even that is assuming that the entire risk difference was due to AD and not to some other variable that wasn't measured.

With so much drug development for AD, I think we are going to be inundated with companies wanting us to hear their message over and over again. One way to do that is to mine clinical trial data for more papers. In Merola and colleagues' article "Safety and Efficacy of Tralokinumab in Older Adults With Moderate-to-Severe Atopic Dermatitis" we see just that. We already know that tralokinumab is effective for moderate to severe AD from past publications of clinical trial data. Here, the investigators report on a subset of the clinical trial data — the data on older adults — and, not surprisingly, the drug worked. The efficacy rate, 17% getting clear or almost clear, doesn't sound particularly exciting compared with the higher rates we've seen for other products, but perhaps that lower rate is due in part to differences in studies. Instead of more cuts of data from the same trials, it would be nice to see how tralokinumab compares with other AD treatments on a head-to-head basis.

I was excited to see that the study included the use of objective electronic monitoring of sleep quality. This was done using wrist actigraphy, devices on the wrist that measure acceleration movements. What a great tool this could be for measuring how much scratching our patients are doing! With devices like these measuring movements objectively, we wouldn't have to rely on patients' self-report of itch or sleep quality. Sadly, these monitors did not show any meaningful differences between the dupilumab and placebo groups. This technology holds great promise but it isn't yet ready for prime-time assessment of scratching or sleep.

The title of Chiesa Fuxench and colleagues' article, "Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis," might be scary to our patients. The authors reported that "children and adults with AD had an increased risk of IBD [inflammatory bowel disease]." The authors concluded, "Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms." Bah, humbug, I say!

Be careful when someone tells you there is increased risk. This study was done exceptionally well by an exceptionally good research team. They were working with a huge database and included many controls to ensure that their findings weren't due to chance. And while they did find an "increased risk," they proved — rather conclusively, I believe — that the increased risk is tiny and not something we need to worry about.

The results of this study suggest that there is a scientific link between AD and IBD, probably some genetic inflammatory signaling contributing to both conditions. But even in the highest-risk group, it would take seeing well over 1000 patients for a year to see one more case of IBD due to AD. This article is a good foundation for researchers who want to explore the underlying connection between AD and IBD. The study is an even better foundation for physicians who want to reassure patients that there is little to no meaningful increased risk for IBD in patients with AD.

Am I allowed to just say "Ditto!"? Wan and colleagues' article "Incidence of Cardiovascular Disease and Venous Thromboembolism in Patients with Atopic Dermatitis" does show a statistically significant increased risk for cardiovascular (CV) disease in patients with AD. Is that increase clinically significant? This study was also exceptionally well done by an exceptionally good research team. They concluded, "Atopic dermatitis, particularly when severe, is associated with increased risks of venous thromboembolism and CV disease, which may influence the monitoring of patients and selection of treatments for AD." I look at their findings and conclude that AD, even when severe, is associated with little if any clinically meaningful increased risks for venous thromboembolism or CV disease, and we don't need to add any special CV monitoring of AD patients.

The key data are presented in Table 2 of their manuscript. In children, the risk for deep vein thrombosis (DVT) in those with severe AD was about 3 times (0.16) that of those with no AD (0.05). But those numbers are per 1000 patient-years. Therefore, the increased risk is 0.16 - 0.05 = 0.11/1000 patient-years. Thus, you'd expect to see one more case of DVT per year in every 9000 children with severe AD. Does that mean we need to monitor all 9000 for DVT? Would that be cost-effective? Might the monitoring cause more problems than it would solve?

CV disease is much more common in adults than in children, but still, with a difference in risk of about 0.5-1 per 1000 patient-years, you'd only expect one more event due to AD in every 1000-2000 patients, and even that is assuming that the entire risk difference was due to AD and not to some other variable that wasn't measured.

With so much drug development for AD, I think we are going to be inundated with companies wanting us to hear their message over and over again. One way to do that is to mine clinical trial data for more papers. In Merola and colleagues' article "Safety and Efficacy of Tralokinumab in Older Adults With Moderate-to-Severe Atopic Dermatitis" we see just that. We already know that tralokinumab is effective for moderate to severe AD from past publications of clinical trial data. Here, the investigators report on a subset of the clinical trial data — the data on older adults — and, not surprisingly, the drug worked. The efficacy rate, 17% getting clear or almost clear, doesn't sound particularly exciting compared with the higher rates we've seen for other products, but perhaps that lower rate is due in part to differences in studies. Instead of more cuts of data from the same trials, it would be nice to see how tralokinumab compares with other AD treatments on a head-to-head basis.

I was excited to see that the study included the use of objective electronic monitoring of sleep quality. This was done using wrist actigraphy, devices on the wrist that measure acceleration movements. What a great tool this could be for measuring how much scratching our patients are doing! With devices like these measuring movements objectively, we wouldn't have to rely on patients' self-report of itch or sleep quality. Sadly, these monitors did not show any meaningful differences between the dupilumab and placebo groups. This technology holds great promise but it isn't yet ready for prime-time assessment of scratching or sleep.

The title of Chiesa Fuxench and colleagues' article, "Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis," might be scary to our patients. The authors reported that "children and adults with AD had an increased risk of IBD [inflammatory bowel disease]." The authors concluded, "Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms." Bah, humbug, I say!

Be careful when someone tells you there is increased risk. This study was done exceptionally well by an exceptionally good research team. They were working with a huge database and included many controls to ensure that their findings weren't due to chance. And while they did find an "increased risk," they proved — rather conclusively, I believe — that the increased risk is tiny and not something we need to worry about.

The results of this study suggest that there is a scientific link between AD and IBD, probably some genetic inflammatory signaling contributing to both conditions. But even in the highest-risk group, it would take seeing well over 1000 patients for a year to see one more case of IBD due to AD. This article is a good foundation for researchers who want to explore the underlying connection between AD and IBD. The study is an even better foundation for physicians who want to reassure patients that there is little to no meaningful increased risk for IBD in patients with AD.

Am I allowed to just say "Ditto!"? Wan and colleagues' article "Incidence of Cardiovascular Disease and Venous Thromboembolism in Patients with Atopic Dermatitis" does show a statistically significant increased risk for cardiovascular (CV) disease in patients with AD. Is that increase clinically significant? This study was also exceptionally well done by an exceptionally good research team. They concluded, "Atopic dermatitis, particularly when severe, is associated with increased risks of venous thromboembolism and CV disease, which may influence the monitoring of patients and selection of treatments for AD." I look at their findings and conclude that AD, even when severe, is associated with little if any clinically meaningful increased risks for venous thromboembolism or CV disease, and we don't need to add any special CV monitoring of AD patients.

The key data are presented in Table 2 of their manuscript. In children, the risk for deep vein thrombosis (DVT) in those with severe AD was about 3 times (0.16) that of those with no AD (0.05). But those numbers are per 1000 patient-years. Therefore, the increased risk is 0.16 - 0.05 = 0.11/1000 patient-years. Thus, you'd expect to see one more case of DVT per year in every 9000 children with severe AD. Does that mean we need to monitor all 9000 for DVT? Would that be cost-effective? Might the monitoring cause more problems than it would solve?

CV disease is much more common in adults than in children, but still, with a difference in risk of about 0.5-1 per 1000 patient-years, you'd only expect one more event due to AD in every 1000-2000 patients, and even that is assuming that the entire risk difference was due to AD and not to some other variable that wasn't measured.

With so much drug development for AD, I think we are going to be inundated with companies wanting us to hear their message over and over again. One way to do that is to mine clinical trial data for more papers. In Merola and colleagues' article "Safety and Efficacy of Tralokinumab in Older Adults With Moderate-to-Severe Atopic Dermatitis" we see just that. We already know that tralokinumab is effective for moderate to severe AD from past publications of clinical trial data. Here, the investigators report on a subset of the clinical trial data — the data on older adults — and, not surprisingly, the drug worked. The efficacy rate, 17% getting clear or almost clear, doesn't sound particularly exciting compared with the higher rates we've seen for other products, but perhaps that lower rate is due in part to differences in studies. Instead of more cuts of data from the same trials, it would be nice to see how tralokinumab compares with other AD treatments on a head-to-head basis.

Key clinical point: The incidence of rheumatoid arthritis (RA) during the pandemic period was significantly higher in individuals who did vs did not develop COVID-19, with patients age 51-60 years having the seemingly highest risk.

Major finding: The incidence rates of developing seropositive RA (incidence rate ratio [IRR] 1.60; 95% CI 1.16-2.22) and unspecified RA (IRR 2.93; 95% CI 2.04-4.19) during the pandemic period (2020-2022) were significantly higher in patients with vs without previous COVID-19, with the incidence rates being the highest in the age group of 51-60 years vs the age group of 18-30 years (hazard ratio 9.16; 95% CI 7.24-11.59).

Study details: This retrospective, population-based cohort study analyzed the data of 3,335,084 individuals from the COOSALUD EPS registry (Columbia).

Disclosures: This study was supported by funds from COOSALUD EPS, Columbia. JS Marín and J-M Anaya declared employment with and receiving financial support from COOSALUD EPS, respectively.

Source: Marín JS et al. Increased incidence of rheumatoid arthritis after COVID-19. Autoimmun Rev. 2023;22(10):103409 (Aug 18). doi: 10.1016/j.autrev.2023.103409

Key clinical point: The incidence of rheumatoid arthritis (RA) during the pandemic period was significantly higher in individuals who did vs did not develop COVID-19, with patients age 51-60 years having the seemingly highest risk.

Major finding: The incidence rates of developing seropositive RA (incidence rate ratio [IRR] 1.60; 95% CI 1.16-2.22) and unspecified RA (IRR 2.93; 95% CI 2.04-4.19) during the pandemic period (2020-2022) were significantly higher in patients with vs without previous COVID-19, with the incidence rates being the highest in the age group of 51-60 years vs the age group of 18-30 years (hazard ratio 9.16; 95% CI 7.24-11.59).

Study details: This retrospective, population-based cohort study analyzed the data of 3,335,084 individuals from the COOSALUD EPS registry (Columbia).

Disclosures: This study was supported by funds from COOSALUD EPS, Columbia. JS Marín and J-M Anaya declared employment with and receiving financial support from COOSALUD EPS, respectively.

Source: Marín JS et al. Increased incidence of rheumatoid arthritis after COVID-19. Autoimmun Rev. 2023;22(10):103409 (Aug 18). doi: 10.1016/j.autrev.2023.103409

Key clinical point: The incidence of rheumatoid arthritis (RA) during the pandemic period was significantly higher in individuals who did vs did not develop COVID-19, with patients age 51-60 years having the seemingly highest risk.

Major finding: The incidence rates of developing seropositive RA (incidence rate ratio [IRR] 1.60; 95% CI 1.16-2.22) and unspecified RA (IRR 2.93; 95% CI 2.04-4.19) during the pandemic period (2020-2022) were significantly higher in patients with vs without previous COVID-19, with the incidence rates being the highest in the age group of 51-60 years vs the age group of 18-30 years (hazard ratio 9.16; 95% CI 7.24-11.59).

Study details: This retrospective, population-based cohort study analyzed the data of 3,335,084 individuals from the COOSALUD EPS registry (Columbia).

Disclosures: This study was supported by funds from COOSALUD EPS, Columbia. JS Marín and J-M Anaya declared employment with and receiving financial support from COOSALUD EPS, respectively.

Source: Marín JS et al. Increased incidence of rheumatoid arthritis after COVID-19. Autoimmun Rev. 2023;22(10):103409 (Aug 18). doi: 10.1016/j.autrev.2023.103409

Key clinical point: Multimorbidity was more prevalent in women vs men with rheumatoid arthritis (RA), with psychological and musculoskeletal conditions being more prevalent in women and cardiovascular-related conditions being more prevalent in men, thus highlighting the need for individualized treatment plans.

Major finding: Among patients with RA age 18-50 years, women vs men were at higher risk for ≥ 2 morbidities (difference in adjusted absolute risk [Δ] 7.5 percentage points; P < .001) and ≥ 5 morbidities (Δ 4.4 percentage points; P < .001). Moreover, the prevalence of psychological and musculoskeletal conditions was higher in women vs men with RA, whereas the prevalence of cardiovascular-related conditions was higher in men vs women with RA (all P < .05).

Study details: This cross-sectional analysis of national administrative claims data from the OptumLabs Data Warehouse included 154,391 patients with RA who were matched with 154,391 comparator individuals without RA.

Disclosures: This study was supported by grants from the US National Institutes of Health and other sources. The authors declared no conflicts of interest. Two authors declared receiving unrelated funding support from various sources.

Source: Stevens MA et al. Disparities in multimorbidity and comorbidities in rheumatoid arthritis by sex acrossthe lifespan. Rheumatology (Oxford). 2023 (Aug 31). doi: 10.1093/rheumatology/kead454

Key clinical point: Multimorbidity was more prevalent in women vs men with rheumatoid arthritis (RA), with psychological and musculoskeletal conditions being more prevalent in women and cardiovascular-related conditions being more prevalent in men, thus highlighting the need for individualized treatment plans.

Major finding: Among patients with RA age 18-50 years, women vs men were at higher risk for ≥ 2 morbidities (difference in adjusted absolute risk [Δ] 7.5 percentage points; P < .001) and ≥ 5 morbidities (Δ 4.4 percentage points; P < .001). Moreover, the prevalence of psychological and musculoskeletal conditions was higher in women vs men with RA, whereas the prevalence of cardiovascular-related conditions was higher in men vs women with RA (all P < .05).

Study details: This cross-sectional analysis of national administrative claims data from the OptumLabs Data Warehouse included 154,391 patients with RA who were matched with 154,391 comparator individuals without RA.

Disclosures: This study was supported by grants from the US National Institutes of Health and other sources. The authors declared no conflicts of interest. Two authors declared receiving unrelated funding support from various sources.

Source: Stevens MA et al. Disparities in multimorbidity and comorbidities in rheumatoid arthritis by sex acrossthe lifespan. Rheumatology (Oxford). 2023 (Aug 31). doi: 10.1093/rheumatology/kead454

Key clinical point: Multimorbidity was more prevalent in women vs men with rheumatoid arthritis (RA), with psychological and musculoskeletal conditions being more prevalent in women and cardiovascular-related conditions being more prevalent in men, thus highlighting the need for individualized treatment plans.

Major finding: Among patients with RA age 18-50 years, women vs men were at higher risk for ≥ 2 morbidities (difference in adjusted absolute risk [Δ] 7.5 percentage points; P < .001) and ≥ 5 morbidities (Δ 4.4 percentage points; P < .001). Moreover, the prevalence of psychological and musculoskeletal conditions was higher in women vs men with RA, whereas the prevalence of cardiovascular-related conditions was higher in men vs women with RA (all P < .05).

Study details: This cross-sectional analysis of national administrative claims data from the OptumLabs Data Warehouse included 154,391 patients with RA who were matched with 154,391 comparator individuals without RA.

Disclosures: This study was supported by grants from the US National Institutes of Health and other sources. The authors declared no conflicts of interest. Two authors declared receiving unrelated funding support from various sources.

Source: Stevens MA et al. Disparities in multimorbidity and comorbidities in rheumatoid arthritis by sex acrossthe lifespan. Rheumatology (Oxford). 2023 (Aug 31). doi: 10.1093/rheumatology/kead454

Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.

Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.

Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.

Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0

Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.

Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.

Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.

Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0

Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.

Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.

Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.

Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0

Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).

Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).

Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.

Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.

Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3

Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).

Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).

Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.

Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.

Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3

Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).

Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).

Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.

Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.

Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3