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Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source