TWENTY-SEVENTH ISSUE
february 1, 2023
Association of Lipid-Lowering Drugs With Risk of Psoriasis
JAMA Dermatology
JAMA Dermatology
Statins step aside… there’s a new golden child of lipid lowering therapy!
As lipid pathways contribute to the pathogenesis of psoriasis, lipid lowering agents have been proposed to serve as modifying agents for this disease. This large-scale, mendelian randomization study investigated the association between psoriasis risk and genetically proxied lipid lowering therapeutics using two European populations, which included 12,116 patients with psoriasis and 1.3 million patients with a low density lipoprotein (LDL) measurement. Exposure to statins (targeting HMG CoA reductase, HMGCR), ezetimibe (targeting Niemann-Pick C1-like 1, NPCL1), and alirocumab (targeting proprotein convertase subtilisin/kexin type 9, PCSK9) was examined.
What did they find?
Main Takeaways: PCSK9 may be involved in psoriasis pathogenesis, and therefore, inhibiting drugs such as alirocumab may aid in reducing the risk of developing psoriasis.
As lipid pathways contribute to the pathogenesis of psoriasis, lipid lowering agents have been proposed to serve as modifying agents for this disease. This large-scale, mendelian randomization study investigated the association between psoriasis risk and genetically proxied lipid lowering therapeutics using two European populations, which included 12,116 patients with psoriasis and 1.3 million patients with a low density lipoprotein (LDL) measurement. Exposure to statins (targeting HMG CoA reductase, HMGCR), ezetimibe (targeting Niemann-Pick C1-like 1, NPCL1), and alirocumab (targeting proprotein convertase subtilisin/kexin type 9, PCSK9) was examined.
What did they find?
- UK BioBank data demonstrated a decreased risk of psoriasis with PCSK9 inhibition (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003)
- Similarly, FinnGen showed decreased risk of psoriasis with PCSK9 inhibition (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002)
- HMGCR and NPCL1 exposure did not significantly reduce risk of psoriasis
Main Takeaways: PCSK9 may be involved in psoriasis pathogenesis, and therefore, inhibiting drugs such as alirocumab may aid in reducing the risk of developing psoriasis.
Acne itself may be associated with increased incidence of IBD
Journal of The American Academy of Dermatology
Irritable bowel disease AND acne? Talk about a pain in the butt…
Early case reports have suggested a correlation between isotretinoin use and development of inflammatory bowel disease (IBD). However, researchers sought to find out whether acne treatments (i.e. isotretinoin or oral antibiotics) versus simply the diagnosis of acne itself was related to increased risk of IBD.
In this matched cohort study, researchers analyzed TriNetX database ICD-10 codes from 2001-2022 to identify 351,670 patients with acne and 353,381 control patients without acne. The primary outcome was a new diagnosis of IBD (UC or Crohn’s identified by ICD-10 code) within 1 year of acne diagnosis or first treatment.
What did they find?
Early case reports have suggested a correlation between isotretinoin use and development of inflammatory bowel disease (IBD). However, researchers sought to find out whether acne treatments (i.e. isotretinoin or oral antibiotics) versus simply the diagnosis of acne itself was related to increased risk of IBD.
In this matched cohort study, researchers analyzed TriNetX database ICD-10 codes from 2001-2022 to identify 351,670 patients with acne and 353,381 control patients without acne. The primary outcome was a new diagnosis of IBD (UC or Crohn’s identified by ICD-10 code) within 1 year of acne diagnosis or first treatment.
What did they find?
- Results showed no significantly increased risk of IBD in patients with acne who were treated with oral tetracyclines compared to patients with acne with no systemic treatment (Odds ratio [OR] 1.00; 95% CI 0.82-1.22)
- Similarly, those with acne treated with isotretinoin showed no significantly increased incidence of IBD compared to untreated acne patients (OR 1.29; 95% CI 0.64-2.59)
- Of particular interest, there was a significant association between acne diagnosis and increased incidence of IBD (Odds ratio [OR] 1.42; 95% CI 1.23-1.65)
Baricitinib blocks cytokine mediated downregulation of PAD1 in human keratinocytes
Journal of Investigative Dermatology
What do you call a quick diagnosis of atopic dermatitis? A rash decision!
Atopic dermatitis (AD) is a chronic inflammatory skin condition featuring disruption of the skin barrier and dysregulation of the immune system. Epidermal differentiation requires several molecular changes, including deimination of proteins (which refers to the conversion of peptidyl-arginine into peptidyl-citrulline by peptidylarginine deaminases; PADs). Since deimination is important for several other skin conditions (psoriasis), the authors sought to study PADs in patients with AD.
What they found:
Main findings: PAD1 levels and filaggrin deimination were reduced in skin of patients with AD, supporting that impaired elimination contributes to skin inflammation. Furthermore, these results suggest that the JAK signaling pathway may be activated by cytokines to promote inflammation in keratinocytes and could be a potential treatment target.
Atopic dermatitis (AD) is a chronic inflammatory skin condition featuring disruption of the skin barrier and dysregulation of the immune system. Epidermal differentiation requires several molecular changes, including deimination of proteins (which refers to the conversion of peptidyl-arginine into peptidyl-citrulline by peptidylarginine deaminases; PADs). Since deimination is important for several other skin conditions (psoriasis), the authors sought to study PADs in patients with AD.
What they found:
- They demonstrated that lesional AD skin had decreased PAD1 protein expression compared to healthy skin
- They found a reduction of deimination of filaggrin in lesional skin compared to nonlesional skin of AD patients
- They found that the addition of JAK inhibitors, such as baricitinib, could prevent the dramatic decrease in PAD1 expression
- AD skin also features chronic inflammation, characterized by overexpression of Th2 cytokines and IL22
- They found that addition of select cytokines and combinations of cytokines could reduce PAD1 expression in keratinocytes
Main findings: PAD1 levels and filaggrin deimination were reduced in skin of patients with AD, supporting that impaired elimination contributes to skin inflammation. Furthermore, these results suggest that the JAK signaling pathway may be activated by cytokines to promote inflammation in keratinocytes and could be a potential treatment target.
DaxibotulinumtoxinA-lanm injection (DAXI) can simultaneously treat glabellar, forehead, and lateral canthal lines
Journal of Investigative Dermatology
Looking to treat wrinkles? Use this medication for DAXImum effect!
DaxibotulinumtoxinA-lanm injection (DAXI) is a novel botulinum toxin Type A formulation in development for aesthetic and therapeutic indications. Researchers sought to evaluate the efficacy and safety of DAXI for simultaneous treatment of moderate or severe glabellar (GL), forehead (FHL), and lateral canthal (LCL) lines through an open label, single-arm Phase 2 study of 48 patients.
What did they find?
- Patients received a single DAXI treatment: DAXI 40U for GL, DAXI 32U for FHL, and DAXI 48U for LCL
- At Week 4, most patients achieved none or mild wrinkle severity: GL (96%), FHL (96), and LCL (92%)
- Median time to loss of “none or mild wrinkle severity” (i.e. when it starts to lose efficacy) among all patients were: 24.6 weeks (GL), 20.9 weeks (FHL), and 24.9 weeks (LCL)
- Adverse events were rare with less than 5 patients experiencing them: injection-site erythema (60%), facial discomfort (40%), and headache (20%)
Main Takeaway: This study provided evidence for the high degree of efficacy, safety, and duration of effects for DAXI in the treatment of GL, FHL, and LCL simultaneously.