Key clinical point: Methotrexate (MTX)-related side effects were more prevalent in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA), whereas tumor necrosis factor inhibitor (TNFi)-related side effects were equally prevalent in patients with PsA and RA.

Major finding: In the first year, a higher proportion of patients with PsA vs RA reported MTX-related side effects (44.8% vs 29.4%), but similar proportions of patients with PsA (24.2%) and RA (22.8%) reported TNFi-related side effects. Patients with PsA vs RA were 1.8 times more likely to experience side effects with MTX (odds ratio 1.77; 95% CI 1.21-2.60).

Study details: Findings are from a retrospective cohort study including new initiators of MTX (PsA: n = 116 and RA: n = 4247) and TNFi (PsA: n = 124 and RA: n = 4361).

Disclosures: This study was funded by Amgen Inc. Two authors declared being employees or owning stocks in Amgen. The other authors declared receiving grants, funding, honoraria, or consulting fees from several sources, including Amgen.

Source: Ogdie A et al. Side effects of methotrexate and tumor necrosis factor inhibitors: Differences in tolerability among patients with psoriatic arthritis and rheumatoid arthritis. ACR Open Rheumatol. 2022 (Aug 15). Doi: 10.1002/acr2.11467

Key clinical point: Methotrexate (MTX)-related side effects were more prevalent in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA), whereas tumor necrosis factor inhibitor (TNFi)-related side effects were equally prevalent in patients with PsA and RA.

Major finding: In the first year, a higher proportion of patients with PsA vs RA reported MTX-related side effects (44.8% vs 29.4%), but similar proportions of patients with PsA (24.2%) and RA (22.8%) reported TNFi-related side effects. Patients with PsA vs RA were 1.8 times more likely to experience side effects with MTX (odds ratio 1.77; 95% CI 1.21-2.60).

Study details: Findings are from a retrospective cohort study including new initiators of MTX (PsA: n = 116 and RA: n = 4247) and TNFi (PsA: n = 124 and RA: n = 4361).

Disclosures: This study was funded by Amgen Inc. Two authors declared being employees or owning stocks in Amgen. The other authors declared receiving grants, funding, honoraria, or consulting fees from several sources, including Amgen.

Source: Ogdie A et al. Side effects of methotrexate and tumor necrosis factor inhibitors: Differences in tolerability among patients with psoriatic arthritis and rheumatoid arthritis. ACR Open Rheumatol. 2022 (Aug 15). Doi: 10.1002/acr2.11467

Key clinical point: Methotrexate (MTX)-related side effects were more prevalent in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA), whereas tumor necrosis factor inhibitor (TNFi)-related side effects were equally prevalent in patients with PsA and RA.

Major finding: In the first year, a higher proportion of patients with PsA vs RA reported MTX-related side effects (44.8% vs 29.4%), but similar proportions of patients with PsA (24.2%) and RA (22.8%) reported TNFi-related side effects. Patients with PsA vs RA were 1.8 times more likely to experience side effects with MTX (odds ratio 1.77; 95% CI 1.21-2.60).

Study details: Findings are from a retrospective cohort study including new initiators of MTX (PsA: n = 116 and RA: n = 4247) and TNFi (PsA: n = 124 and RA: n = 4361).

Disclosures: This study was funded by Amgen Inc. Two authors declared being employees or owning stocks in Amgen. The other authors declared receiving grants, funding, honoraria, or consulting fees from several sources, including Amgen.

Source: Ogdie A et al. Side effects of methotrexate and tumor necrosis factor inhibitors: Differences in tolerability among patients with psoriatic arthritis and rheumatoid arthritis. ACR Open Rheumatol. 2022 (Aug 15). Doi: 10.1002/acr2.11467

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Among patients with psoriatic arthritis (PsA) women experienced significantly higher disease burden than men despite similar disease activity and comparable treatments.

Major finding: Despite similar disease duration (P  =  .42), disease presentation, and biologic use (P  =  .38), women vs men had worse mean quality-of-life (0.80 vs 0.82; P  =  .02) and disability and physical functioning (0.56 vs 0.41; P < .01) scores, greater degree of work activity impairment (27.9% vs 24.6%; P < .01), and higher pain and fatigue scores (P < .01).

Study details: This study analyzed the data of 2270 patients with PsA (1223 men and 1047 women) from the Adelphi PsA Disease Specific Programme.

Disclosures: This study was funded by Janssen Research & Development, LLC. Three authors declared being employees of Janssen and owning stocks in Janssen/Johnson and Johnson. Some authors declared receiving research grants and consulting fees from several sources, including Janssen.

Source: Gossec L et al. Women with psoriatic arthritis experience higher disease burden than men: Findings from a real-world survey in the USA and Europe. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220154

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5 mg/dL) and the remaining had high CRP levels (>0.5 mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5 mg/dL) and the remaining had high CRP levels (>0.5 mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5 mg/dL) and the remaining had high CRP levels (>0.5 mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5mg/dL) and the remaining had high CRP levels (>0.5mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5mg/dL) and the remaining had high CRP levels (>0.5mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

Key clinical point: Levels of C-reactive protein (CRP), a classic inflammatory marker, do not adequately reflect the level of disease activity (DA) in patients with psoriatic arthritis (PsA).

Major finding: CRP status was only associated with the erythrocyte sedimentation rate (odds ratio 1.04; P  =  .005) and not with any DA-related parameter. Among patients with normal CRP levels, a substantial proportion (45.9%) of patients were in non-minimal DA state, with 21.2% having moderate DA and 5.9% having high DA.

Study details: Findings are from a cross-sectional study including 128 patients with PsA, of which 66.4% had normal CRP levels (≤0.5mg/dL) and the remaining had high CRP levels (>0.5mg/dL).

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

Source: Gialouri CG et al. Normal C-reactive protein in active psoriatic arthritis: Results from real-world clinical practice. Ther Adv Musculoskelet Dis. 2022 (Sep 5). Doi: 10.1177/1759720X221122417

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.

Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.

“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.

iStock/ThinkStock

The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.

“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.

The WATERFALL trial results were published in the New England Journal of Medicine.

The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
 

Trial details

The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.

Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.

Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.

A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.

The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).

“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.

This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).

Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.

“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
 

‘Landmark’ trial

This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.

“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.

Dr. Gardner said the WATERFALL trial results lead to several conclusions.

First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.

Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.

Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.

Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.

“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.

“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.

Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).

A version of this article first appeared on Medscape.com.

Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.

Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.

“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.

iStock/ThinkStock

The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.

“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.

The WATERFALL trial results were published in the New England Journal of Medicine.

The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
 

Trial details

The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.

Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.

Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.

A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.

The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).

“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.

This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).

Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.

“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
 

‘Landmark’ trial

This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.

“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.

Dr. Gardner said the WATERFALL trial results lead to several conclusions.

First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.

Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.

Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.

Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.

“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.

“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.

Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).

A version of this article first appeared on Medscape.com.

Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.

Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.

“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.

iStock/ThinkStock

The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.

“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.

The WATERFALL trial results were published in the New England Journal of Medicine.

The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
 

Trial details

The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.

Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.

Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.

A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.

The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).

“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.

This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).

Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.

“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
 

‘Landmark’ trial

This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.

“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.

Dr. Gardner said the WATERFALL trial results lead to several conclusions.

First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.

Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.

Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.

Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.

“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.

“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.

Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).

A version of this article first appeared on Medscape.com.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.