Amanda Kvist-Hansen

Over the past two decades, numerous highly effective biological treatments have been developed for patients with moderate-to-severe psoriasis. As a result of more effective therapies, treatment goals have shifted from a 50% to a 90% reduction in psoriasis area and severity index. Although randomized controlled trials provide some insight, they often include only a subset of patients, have short durations, and do not compare different treatments. Many patients respond well to these new treatments; however, some do not respond at all, whereas others experience a loss of effectiveness after an initial response. No definitive guidelines on the best time to start treatment or on how to choose the most suitable treatment for an individual patient have yet been established. Furthermore, it remains uncertain whether optimal treatment or specific therapy reduces the risk of developing comorbidities. Real-world data have revealed adverse effects, such as tuberculosis reactivation with tumor necrosis factor inhibitors, worsening of inflammatory bowel disease with interleukin-17 inhibitors, and potential cardiovascular events associated with particularly interleukin-12/23 inhibition. Studies from both clinical trials and real-world settings have also shown that patients with high body mass index, smokers, older individuals, and those with prior biological treatments tend to have poorer treatment outcomes. Recently, studies have indicated that genetic markers such as HLA-C*06:02, initial treatment response, and post-initiation drug concentration levels can predict treatment response. The integration of genetic markers, clinical data, and advanced technologies may aid in developing more personalized treatment plans for patients in the future.

Accumulating evidence supports the association between altered salivary microbiota and inflammatory diseases. The existing literature on the salivary microbiota in patients with psoriasis is limited. However, differences in the prevalence of Candida species and abundance of several bacterial taxa in saliva have been found between patients and controls. This study aimed to investigate the differences in the composition and functional potential of salivary microbiota in patients with psoriasis compared to their cohabiting partners and healthy controls. Samples from 115 of 123 individuals qualified for statistical analysis: patients with psoriasis who did not receive systemic anti-psoriatic treatment (n=47); cohabiting partners (n=21); and age-, sex-, and BMI-matched healthy controls (n=47). One saliva sample was collected from each participant and analysed by shotgun metagenomic sequencing. A difference in the α-diversity of bacterial species was observed exclusively between patients and controls, with a lower diversity in patients (p=0.041). Variation in bacterial composition (β-diversity) was influenced by smoking (p=0.001) and diet (p=0.025) but not by group status. Using a linear regression model adjusted for smoking and diet, we identified four bacterial classes and five species that were significantly different between the patient, partner, and control groups. One Kyoto Encyclopedia of Genes and Genomes module differed significantly between patients with psoriasis and their partners. No differences in Candida species or abundance were found among the three groups. Comparison of salivary microbiota at the levels of bacterial diversity, composition, and predicted function indicated that psoriasis cases are characterised by dysbiosis.

As women of childbearing potential constitute a considerable portion of the total psoriasis population, dermatologists must consider both the clinical and psychosocial implications of psoriasis when treating these patients. This review summarizes key clinical considerations when treating women of childbearing potential with psoriasis, regarding family planning, pregnancy, and the postpartum period, aiming to assist in identifying common concerns within this population. Many women report initiating the discussion on family planning but having limited access to information. Concerns about the impact of psoriasis and its treatment on fertility, pregnancy, and lactation are common, and lack of adequate information can lead to irrevocable decisions. Despite conflicting results, current evidence suggests a potential negative correlation between moderate-to-severe psoriasis and fertility. Studies on adverse maternal and neonatal events associated with psoriasis show inconsistent outcomes and should be communicated with caution. With the increase in available treatment options during pregnancy and lactation, particularly in cases of severe psoriasis, personalized treatment plans are becoming more achievable, allowing dermatologists to better address the needs of their patients. The majority of patients can be treated during pregnancy with topical treatments or ultraviolet-B irradiation. While the general recommendation is to stop systemic treatment before conception, decisions should be made on an individualized basis. If treatment cannot be discontinued, tumor necrosis factor-α inhibitors and cyclosporine can be used. It is essential to inform parents of the additional risks associated with live or live-attenuated vaccines in cases where the mother has received systemic treatment during pregnancy and to delay vaccinations accordingly.

Background: Biomarkers of low-grade systemic inflammation have been reported to be higher in patients with psoriasis than in healthy controls. However, it is unknown whether this low-grade systemic inflammation contributes to the development of psoriasis or is merely a consequence. Objectives: To investigate whether low-grade systemic inflammation, measured as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) or C-reactive protein (CRP), is an independent risk factor for psoriasis. Methods: We used data from the Copenhagen General Population Study, a prospective cohort study of the Danish general population where individuals aged 20–100 years were enrolled between 2003 and 2015. Upon enrolment in the study, all individuals underwent a physical examination, completed an extensive self-reported questionnaire regarding lifestyle, and provided blood samples, from which SII, NLR and CRP were measured. Psoriasis was identified using International Classification of Diseases codes with individual linkage to the Danish National Patient Registry. Associations between SII, NLR and CRP and psoriasis were estimated using hazard ratios from Cox proportional hazard regression models. Analyses were adjusted for potential confounders including sex, age, smoking, alcohol consumption, physical activity, educational level, hypertension, dyslipidaemia and obesity. Results: We included 105 418 individuals with a median age of 58 years, 55% of whom were women. The risk of receiving a diagnosis of psoriasis increased with increasing levels of SII, NLR and CRP. In individuals with high levels (> 90th percentile) of SII, NLR and CRP, the multivariable adjusted hazard ratios were 1.78 [95% confidence interval (CI) 1.41–2.24], 1.56 (95% CI 1.22–1.99) and 2.83 (95% CI 2.27–3.51), respectively, compared with individuals with low levels. Results were similar but slightly attenuated when we used topical calcipotriol (alone or in combination with corticosteroids) for mild psoriasis. Conclusions: We found that low-grade systemic inflammation, as measured by SII, NLR and CRP, was an independent risk factor for psoriasis, especially moderate-to-severe disease. These findings support the hypothesis that low-grade systemic inflammation may contribute to the pathogenesis of psoriasis rather than simply being a consequence of the disease.

This study investigated humoral immunity to mRNA-based COVID-19 vaccines after a booster dose in patients with psoriasis treated with biologics or methotrexate. We observed an increase in humoral responses in both patients and control participants after a booster vaccine. At 12 months, both groups showed positive humoral responses, but patients had significantly lower levels of IgG and neutralizing indexes than the control group. It is unknown if the observed difference has clinical relevance.

For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune–inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67–2.86) vs. 2.54 (1.88–3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42–1.4) vs. 1.62 (0.96–2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1β, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis.

MRNA-based COVID-19 vaccines have short and long-term efficacy in healthy individuals, but their efficacy in patients with psoriasis receiving immunomodulatory therapy is less studied. To investigate long-term immunity after COVID-19 vaccination in patients with psoriasis receiving immunomodulatory therapy. A prospective cohort study including patients (n = 123) with psoriasis receiving methotrexate (MTX) or biologics and controls (n = 226). Only mRNA-based COVID-19 vaccines administered with standard intervals between doses were investigated. Markers of immunity included SARS-CoV-2 spike-glycoprotein specific IgG and IgA, neutralizing capacity, and interferon-gamma release from T-cells stimulated with peptides of the SARS-CoV-2 spike-glycoprotein. The proportion of IgG responders was lower 6 months after vaccination in patients receiving anti-TNF compared to controls. Anti-TNF treatment was associated with lower IgG levels (β=-0.82, 95% CI -1.38 to -0.25: P = 0.001). The median neutralizing index was lower in the anti-TNF group, 50% inhibition (IQR 37-89) compared to controls, 98% inhibition (IQR 96-99), P < 0.001. Cellular responses were numerically lowest in anti-TNF group. Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity, however, the clinical implications are unknown.