The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.

Clinical Characteristics Associated With Response to Biologics in the Treatment of Psoriasis: A Meta-analysis.

Importance: Clinical characteristics associated with treatment response to biologics in patients with psoriasis have never been systematically investigated. Objective: To evaluate the association between patient clinical characteristics and the effectiveness of biologics in treating psoriasis. Data Sources: PubMed, Embase, and Web of Science were searched from their inception through April 2022. Studies in English language that reported response to biologic treatment at approved doses in patients with psoriasis in relation to their clinical characteristics were included. In addition, eligible studies were identified through a search of the reference lists of the included studies. Study Selection: We only included studies that reported treatment outcomes as Psoriasis Area and Severity Index (PASI) 75 or PASI 90 after 12, 26, and/or 52 weeks of treatment. Both observational studies and randomized clinical trials (RCTs) were considered. Two independent authors conducted the screening process, and 107 studies were assessed for eligibility. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Relevant data were extracted independently by 2 authors. Data were pooled using random-effects models. RCTs and observational studies were pooled in separate analyses. Data were analyzed from June 1, 2023, to August 1, 2023. Main Outcomes and Measures: The primary outcome was PASI 90 at 26 weeks (6 months). Before data collection began, an investigation of the association between the main (and secondary) outcomes and several clinical characteristics was planned. Results: Overall, 40 studies with a total of 21 438 patients were included. Older age (odds ratio [OR], 0.99; 95% CI, 0.98-1.00), previous exposure to biologics (OR, 0.44; 95% CI, 0.29-0.67), higher body mass index (BMI) (OR, 0.96; 95% CI, 0.94-0.99), previous smoking (OR, 0.81; 95% CI, 0.67-0.98), and current smoking (OR, 0.78; 95% CI, 0.66-0.91) were negatively associated with achieving PASI 90 at 6 months in observational studies. In RCTs, only BMI of 30 or higher was negatively associated with treatment response (PASI 90 at 3 months: OR, 0.57; 95% CI, 0.48-0.66). Conclusions and Relevance: This meta-analysis found that patients with psoriasis who smoke or have a history of smoking, as well as those with previous exposure to biologics, older age, or higher BMI, exhibited poorer response to biologics in observational studies. However, it remains unclear whether these clinical characteristics influence treatment response differently for the different biologics available for psoriasis.

Psychological burden, anxiety, depression and quality of life in patients with hand eczema: A systematic review and meta-analysis.

BACKGROUND: Living with hand eczema (HE) has been associated with impaired quality of life (QoL), having anxiety and depression but the magnitude of association is not clear. OBJECTIVES: The aim of this systematic review and meta-analysis was to determine the psychological burden in terms of anxiety, depression and quality of life in patients with HE. METHODS: Several databases were systematically searched. Weighted means with standard deviation (SD) were calculated for disease severity, QoL, depression and/or anxiety scores among patients with HE. For studies presenting QoL, depression and/or anxiety scores in patients with HE and in controls the weighted means were compared with an unpaired t-test. In studies reporting Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI), the correlation between HECSI and DLQI was estimated using Spearman's rank correlation (rs). RESULTS: In total, 81 studies encompassing 17,835 patients with HE and 31,541 controls were included. The weighted mean DLQI was 10.66 (SD 8.93) corresponding to a moderate-to-large effect on QoL and a strong correlation (rs: 0.76, 95% CI:0.56-0.87) between DLQI and HECSI was observed. The mean EQ-5D-VAS was significantly lower in patients with HE compared with controls (68.03 (SD 10.52) vs. 80.63 (SD 1.17), p < 0.00001). Patients with HE had higher mean HADS (Hospital Anxiety and Depression Scale) anxiety score (7.4 vs. 5.8, p = 0.0008) than controls but not higher HADS depression score (6.5 vs. 5.7, p = 0.32). Only one study assessed risk of anxiety, depression and suicidal ideation showing an increased odds of all diseases among patients with HE compared with controls. CONCLUSION: Hand eczema has a moderate-to-severe impact on quality of life with a strong correlation between disease severity and impact on quality of life. Patients with hand eczema have an impact on QoL comparable to other chronic diseases when measured with generic QoL scoring systems.

Response to Interleukin-17A Inhibitors According to Prior Biologic Exposures: A Danish Nationwide Study.

Whether response to an interleukin (IL-17) inhibitor is different in patients with previous exposure to an IL-17 inhibitor compared with patients with exposure to biologics with other cytokine targets remains to be elucidated. Therefore, the aim of this study was to  assess whether previous exposure to an IL-17A inhibitor was associated with worse response than exposure to (an)other biologic(s). All patients in the DERMBIO register treated with an IL-17A inhibitor (secukinumab or ixekizumab) were included. With an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 as response, the proportion of responders treated with IL-17A inhibitors was assessed in patients previously treated with another IL-17A inhibitor and compared with patients with previous exposure to (an)other biologic(s), using a χ2 test. In total, 100, 93 and 83 patients with  previous exposure to an IL-17A inhibitor and 414, 372 and 314 patients with previous exposure to (an) other biologic(s) were assessed after 3, 6 and 12 months, respectively. No differences in the proportion of  patients achieving PASI ≤ 2 were observed between the 2 groups after 3 months (54% vs 57%, p = 0.59), 6months (70% vs 66%, p = 0.42) and 12 months (69% vs 60%, p = 0.14). In conclusion, when treating patients with IL-17A inhibitors the cytokine target of the previous biologic does not appear to affect the  response.

Use of systemic and biological therapy in patients with moderate-to-severe psoriasis.

BACKGROUND: Patients with moderate-to-severe psoriasis are candidates for systemic treatment, but it is unknown how many receive such therapy at a national level in Denmark. OBJECTIVES: We aimed to determine the prevalence of conventional systemic therapy use in patients with moderate-to-severe psoriasis and, further, to investigate the time to discontinuation of conventional systemic therapy and initiation of biological therapy among biologic-naïve patients. METHODS: This registry-based study identified a cohort of patients with psoriasis in Denmark. We estimated the prevalence of moderate-to-severe psoriasis at a national level using registry data. Inverse probability weighting was used to mitigate potential selection bias in the prevalence estimate of moderate-to-severe psoriasis. Analyses were then performed on the weighted cohort. RESULTS: Of patients with psoriasis in Denmark, 10.9% were estimated to have moderate-to-severe psoriasis, of whom 62.3% received either conventional systemic or biological therapy, meaning 37.7% who were considered candidates for systemic therapy did not receive any systemic treatment. The study demonstrated that, comparing previous time periods with more recent years: (i) time on conventional systemic therapy for patients with moderate-to-severe psoriasis has become shorter, with a median (interquartile range) of 3.0 years (0.6-10.0) in 1985-1994 vs. 0.6 years (0.3-2.0) in 2014-2018; (ii) more patients initiated biologics as second-line therapy, with 69.5% in 2010-2013 vs. 71.2% in 2014-2018; and (iii) the median time from initiation of systemic therapy to initiation of biological therapy decreased from 13.3 years (11.5-16.8) in 2010-2013 to 1.9 years (1.7-2.4) in 2014-2018. CONCLUSIONS: This study found that nearly 37.7% of Danish patients with moderate-to-severe psoriasis do not receive systemic treatment even though they would qualify for this. Furthermore, for patients treated with conventional systemics, drug survival decreased during the observation period.

Blood Cell Biomarkers of Inflammation and Cytokine Levels as Predictors of Response to Biologics in Patients with Psoriasis.

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)-1ß, 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-1ß, 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.

Development and internal validation of a diagnostic prediction model for psoriasis severity.

BACKGROUND: While administrative health records such as national registries may be useful data sources to study the epidemiology of psoriasis, they do not generally contain information on disease severity. OBJECTIVES: To develop a diagnostic model to distinguish psoriasis severity based on administrative register data. METHOD: We conducted a retrospective registry-based cohort study using the Danish Skin Cohort linked with the Danish national registries. We developed a diagnostic model using a gradient boosting machine learning technique to predict moderate-to-severe psoriasis. We performed an internal validation of the model by bootstrapping to account for any optimism. RESULTS: Among 4016 adult psoriasis patients (55.8% women, mean age 59 years) included in this study, 1212 (30.2%) patients were identified as having moderate-to-severe psoriasis. The diagnostic prediction model yielded a bootstrap-corrected discrimination performance: c-statistic equal to 0.73 [95% CI: 0.71-0.74]. The internal validation by bootstrap correction showed no substantial optimism in the results with a c-statistic of 0.72 [95% CI: 0.70-0.74]. A bootstrap-corrected slope of 1.10 [95% CI: 1.07-1.13] indicated a slight under-fitting. CONCLUSION: Based on register data, we developed a gradient boosting diagnostic model returning acceptable prediction of patients with moderate-to-severe psoriasis.

Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis.

BACKGROUND: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. OBJECTIVES: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. METHODS: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. RESULTS: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. CONCLUSIONS: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.

Characterization of circulating extracellular traps and immune responses to citrullinated LL37 in psoriasis.

Background: The DNA-binding peptide LL37 is a suspected autoantigen in psoriasis. It can be found in neutrophil extracellular traps (NETs) which have been suggested to play a role in the pathogenesis of the disease. Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, can be implicated in the formation of NETs. We hypothesized that citrullination increases LL37 immunogenicity and that NETs are a source of LL37. Objectives: We aimed to characterize cytokine responses of B cells and T cells to native and citrullinated LL37 (citLL37) and determine the prevalence and composition of circulating NETs in patients with psoriasis and healthy blood donors (HDs). Methods: Mononuclear cells (MNCs) and serum were isolated from 20 HDs and 20 patients with psoriasis. The MNCs were stimulated with native LL37 and citLL37 and the proportion of cytokine-positive B cells and T cells was determined by flow cytometry. Circulating antibodies against native LL37 and citLL37 as well as circulating NETs were measured by ELISA, as was the content of LL37, citLL37, and IgG in the NETs. Results: CitLL37, but not native LL37, induced IFN-γ-production by T cells and B cells from psoriasis patients, as well as IL-10-production by the patients' CD4+ T cells. Serum from 40% of patients and 55% of HDs contained circulating NETs, of which 63% and 27%, respectively, contained LL37. Only two patients had NETs containing citLL37 and IgG antibodies were found in NETs from three patients and one HD. Post-hoc analysis of the cytokines produced by B cells and T cells after stimulation with citLL37 revealed two clusters of patients consisting of 10 high-responders and 9 low-responders. The high-responders were those that had circulating NETs in combination with an earlier age of onset of the disease. Conclusion: Citrullinated but not native LL37 elicits IFN-γ-responses by T cells and B cells from psoriasis patients, particularly those with circulating NETs and early disease onset, suggesting a role of citLL37 as an autoantigen in this subgroup of patients.

Incidence, Risk Factors, and Consequences of Human Alphaherpesvirus Infections in Patients With Psoriasis Who Initiate Methotrexate or Biologic Agents.

BACKGROUND: Immunosuppressive agents may increase the risk of infections with human alphaherpesviruses. METHODS: We included all adult patients with moderate to severe psoriasis who initiated methotrexate (MTX) or biologic agents in a retrospective cohort study. An episode of alphaherpesviruses infection was defined as filling a prescription for systemic acyclovir, valacyclovir, or famciclovir. Using nationwide registries, we determined the incidence, risk factors, 180-day hospital contacts, and 30-day mortality following infection. RESULTS: We included 7294 patients; 4978 (68%) received MTX, and 2316 (32%) biologic agents. The incidence rates (95% confidence intervals) of alphaherpesviruses were 23 (20-27), 26 (19-35), 17 (11-27), and 6.7 (1.3-21) per 1000 person-years of follow-up in patients on MTX, tumor necrosis factor alpha (TNF-α) inhibitors, interleukin 12/23 (IL-12/23) inhibitors, and interleukin 17 (IL-17) inhibitors, respectively. Males had an unadjusted hazard ratio (HR) of 0.47 (P < .001) for alphaherpesvirus infection. Patients on IL-17 inhibitors had an adjusted HR of 0.24 (P = .048) compared to TNF-α inhibitors. Within 180 days after infection, 13%, 7.5%, and <0.5% of patients on MTX, TNF-α inhibitors, and IL-12/23 or IL-17 inhibitors, respectively, had hospital contacts, and the 30-day mortality for all groups was <0.5%. CONCLUSIONS: The incidence and risk of alphaherpesvirus infections were comparable between patients on MTX and TNF-α inhibitors, whereas use of IL-17 inhibitors was associated with a lower risk.

Circulating Brodalumab Levels and Therapy Outcomes in Patients With Psoriasis Treated With Brodalumab: A Case Series.

Importance: Given the possible treatment modalities in psoriasis management, little is known about whether drug monitoring is associated with response rate. Objective: To determine whether drug monitoring is associated with response to brodalumab therapy. Design: A multicenter case series study of patients with psoriasis treated with brodalumab whose treatment with previous IL-17A inhibitor therapy failed. Patients were recruited from the Departments of Dermatology at Gentofte and Aarhus University Hospitals, Denmark, between 2018 and 2020. Patient visits were conducted after 4 and 12 weeks of therapy. Patients not achieving Psoriasis Area and Severity Index 75% improvement from baseline (PASI 75) after 12 weeks were discontinued and considered nonresponders. Patients maintaining PASI 75 response were followed up for up to 52 weeks. Exposure: Treatment with brodalumab, 210 mg, at weeks 0, 1, 2, then every 2 weeks. Main Outcomes and Measures: Outcome measures were PASI reductions vs brodalumab levels and antibrodalumab antibodies. Results: Twenty patients with psoriasis (13 [65%] were male; median age, 50 years [range, 19-66 years]) were included. After 12 weeks of therapy, patients with quantifiable levels of brodalumab (≥0.05 µg/mL) experienced significantly higher PASI reductions than those without (median, 93%; range, 61%-100% vs median, -3; range, -49% to 94%, respectively; P = .006). After 12 weeks of therapy, 4 of 5 patients (80%) not achieving PASI 75 had subquantifiable drug levels (<0.05 µg/mL), although this finding was seen for only 3 of 14 PASI 75 responders (21%). None of 7 patients (35%) with subquantifiable drug levels after 12 weeks of therapy maintained response. No antibrodalumab antibodies were detected in any of the tested samples. Conclusions and Relevance: Results of this case series study suggest that circulating brodalumab level is a factor associated with clinical treatment response. Monitoring patient levels of circulating brodalumab may aid clinical decision-making and help prevent ineffective therapy.

Absolute and Relative Risk of New-Onset Psoriasis Associated With Tumor Necrosis Factor-α Inhibitor Treatment in Patients With Immune-Mediated Inflammatory Diseases: A Danish Nationwide Cohort Study.

Importance: Tumor necrosis factor-α inhibitor (TNFi)-associated psoriasis is a rare adverse event following TNFi treatment. Data on the risk of developing TNFi-associated psoriasis when treated with TNFi are sparse. Objective: To investigate the associated risk between new-onset psoriasis and TNFi treatment compared with nonbiologic conventional treatment. Design, Setting, and Participants: Using Danish national registries (1995-2018), this cohort study included patients with inflammatory bowel disease (IBD) and/or rheumatoid arthritis (RA) who received either conventional therapy or TNFi treatment. Patients may not have been diagnosed with psoriasis prior to initiation of treatment. Patients were followed up for up to 5 years. Cox regression models with robust variance were used to compare the risk of developing any type of psoriasis, nonpustular psoriasis, and pustular psoriasis. Patients receiving conventional therapy were used as reference. Data analysis was performed from January 1995 to December 2018. Exposures: For the present study, the term conventional therapy was used for the nonbiological therapy. For biological therapy, a distinction was made between TNFi treatment and non-TNFi biological therapy. Main Outcomes and Measures: The outcome of psoriasis was defined as a registered International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code of psoriasis and/or having 2 consecutive prescriptions of topical vitamin D analogues. Results: The study included 109 085 patients, of which 62% were female. Median (IQR) age was 50 (34-64) years. Of the included patients, 108 024 received conventional therapy and 20 910 received TNFi treatment. During follow-up, 1471 (1.4%) patients developed any type of psoriasis, of which 1332 developed nonpustular psoriasis, 127 patients developed palmoplantar pustulosis, and 12 patients developed generalized pustulosis. The incidence rates for developing any type of psoriasis per 1000 patient-years were 3.0 (95% CI, 2.9-3.2) for conventional therapy and 7.8 (95% CI, 7.5-8.9) for TNFi. During treatment with TNFi, the hazard ratio was 2.12 (95% CI, 1.87-2.40; P < .001) for developing nonpustular psoriasis and 6.50 (95% CI, 4.60-9.23; P < .001) for pustular psoriasis compared with conventional treatment. Exposure needed for 1 additional patient to be harmed was 241 patient-years for any type of TNFi-associated psoriasis, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis. Conclusions and Relevance: In a Danish nationwide cohort of patients with immune-mediated inflammatory diseases treated with TFNi or conventional treatment and no history of psoriasis, in TFNi-treated patients, nonpustular types of psoriasis constituted the most events, whereas pustular types of psoriasis had the highest relative risk. Although the risk of new-onset psoriasis increased for both nonpustular and pustular types of psoriasis in TFNi-treated patients, the absolute risk remained modest at 241 patient-years of exposure need for 1 additional event and an estimated absolute risk difference around 5 per 1000 patient-years, indicating that the approach to treatment of patients in need of TNFi treatment should not change.

A nationwide population-based cohort study of the incidence of severe and rare infections among adults with psoriasis in Denmark.

BACKGROUND: Patients with psoriasis have a high risk for multiple comorbid conditions. However, few studies have examined the association between psoriasis and severe and rare infections. This study reports the incidence of severe and rare infections (considered as rare in Denmark) among Danish patients with psoriasis, compared with the general population. OBJECTIVES: The objectives of this study were to assess the incidence and risk of severe and rare infections in Danish patients with psoriasis and the matched general population, and to compare this risk for patients with severe or mild psoriasis with that of the general population. METHODS: Data for individuals aged ≥18 years who were alive and resident in the source population were collected from the Danish National Patient Register between 1 January 1997 and 31 December 2018. Individuals with any of the investigated chronic infections prior to inclusion were excluded. Patients with psoriasis were matched (1 : 6) for age and sex with general population controls. Severe infections were defined as infections requiring treatment in a hospital setting and rare infections included HIV, hepatitis B and C, and tuberculosis infections. Incidence rates (IRs) were reported per 100 000 person-years of exposure. Severe psoriasis was defined according to previous or active use of systemic or biological treatment. Patients who never received biological and/or systemic treatment were categorized as having mild psoriasis. RESULTS: A total of 94 450 patients with psoriasis were matched with 566 700 controls. The respective IRs were higher for patients with any psoriasis compared with controls; IR 3104·9 [95% confidence interval (CI) 3066·6 to 3143·7] and IR 2381·1 (95% CI 2367·6 to 2394·6) for any infection, IR 3080·6 (95% CI 3042·5 to 3119·3) and IR 2364·4 (95% CI 2350·9 to 2377·9) for severe infections, and IR 42·9 (95% CI 38·89 to 47·4) and IR 31·8 (95% CI 30·34 to 33·3) for rare infections, respectively. Patients with severe psoriasis had higher IRs of severe or rare infections (IR 3847·7, 95% CI 3754·3 to 3943·4) compared with patients with mild psoriasis and controls. CONCLUSIONS: As the severity of psoriasis increases, so does the risk of severe and rare infections. Therefore, clinicians should be aware of the increased risk of severe and rare infections in patients with severe psoriasis so that early investigation and treatment can be initiated. What is already known about this topic? Few studies have looked at the incidence and prevalence of serious infections (associated with hospitalization) and rare infections including tuberculosis, hepatitis B and C, and HIV among patients with different severities of psoriasis. What does this study add? Patients with psoriasis have an increased risk of severe and rare infections. Clinicians should be aware of the increased risk of severe and rare infections in patients with severe psoriasis so that early investigation and treatment can be initiated.

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries.

OBJECTIVE: Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis. METHODS: We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy. FINDINGS: The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab. INTERPRETATION: Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history. FUNDING: None.

Disease burden, symptoms, and use of analgesics in patients with psoriasis with or without psoriatic arthritis: A cross-sectional study.

BACKGROUND: Patients with psoriasis have an impaired quality of life and higher use of analgesics than the general population. Whether such use is due to skin pain or a consequence of joint pain resulting from psoriatic arthritis (PsA) is not clear. OBJECTIVES: To assess symptoms, disease burden, and use of analgesics in patients with psoriasis with and without PsA. METHOD: Symptoms, general health (EurQol 5-dimension and 5-levels), and use of analgesics were assessed in patients with psoriasis and the general population from the Danish Skin Cohort. RESULTS: We included 4016 patients with psoriasis (847 with concomitant PsA) and 3490 reference individuals. For patients with psoriasis having PsA, itch, skin pain, and/or joint pain was associated with worse general health. Use of opioids within 12 months was observed among 9.0% of the general population, 14.2% of patients with psoriasis without PsA, and 22.7% of patients with concomitant PsA. Of the symptoms, only joint pain was associated with use of analgesics (odds ratio, 3.72 (2.69-5.14); P < .0001). LIMITATIONS: Cross-sectional design. CONCLUSION: Patients with psoriasis (especially concomitant PsA) have a higher use of analgesics compared with the general population, which appears to be a result of increased joint pain.

Impact of methotrexate and adalimumab on immune function of patients with psoriasis.

Patients with psoriasis are commonly treated with methotrexate or biologics. We examined the immune response in a whole blood assay (TruCulture®) to assess the effect of methotrexate and adalimumab. Twenty patients with psoriasis were included and cytokine levels following stimulation with LPS, R848, HKCA, PolyIC, or a blank were investigated before and after 3-6 months of treatment with methotrexate or adalimumab and in patients who had received adalimumab >5 years. Methotrexate only induced minor changes in the cytokine responses, whereas adalimumab affected a wide range of cytokines important for the immune defense towards microorganisms. In the long-term adalimumab treated group, the cytokine levels were almost equivalent to the short-term adalimumab-treated group. Overall, methotrexate was not associated with cytokine suppression. Short and long-term treatment with adalimumab lowered multiple cytokines involved in the immune defense equally emphasizing the need to continuously be aware of the risk of infections in these patients.