Drug Survival of Adalimumab, Secukinumab, and Ustekinumab in Psoriasis as Determined by Either Dose Escalation or Drug Discontinuation during the First 3 Years of Treatment - a Nationwide Cohort Study.

The real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine the real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007-2019), we included patients with psoriasis treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, whereas the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4,313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety), we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59-0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05-1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08-1.42) and adalimumab (HR 2.01, 95% CI 1.82-2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to that of ustekinumab (HR 0.95, 95% CI 0.61-1.49).

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.

Outcomes Following a Mandatory Nonmedical Switch From Adalimumab Originator to Adalimumab Biosimilars in Patients With Psoriasis.

IMPORTANCE: The efficacy of adalimumab biosimilars is similar to that of brand-name adalimumab (Humira, hereinafter originator) in clinical trials. However, limited knowledge about real-world data exists for adalimumab biosimilars. OBJECTIVE: To assess the outcomes following a mandatory nonmedical switch from adalimumab originator to adalimumab biosimilars in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assesses the outcomes following a switch from adalimumab originator to an adalimumab biosimilar. Patients in the Biological Treatment in Danish Dermatology (DERMBIO) registry, a Danish nationwide registry of all patients treated with biologics (including biosimilars) for psoriasis since 2007, were assessed for eligibility. All patients who switched from adalimumab originator to an adalimumab biosimilar between November 1, 2018, and May 1, 2019, were included in the adalimumab biosimilar cohort. All patients with a visit between May 1, 2017, and November 1, 2017, treated with adalimumab originator were included in the adalimumab originator cohort. Data were analyzed from June 1, 2020, to October 10, 2021. EXPOSURE: Switch from adalimumab originator to an adalimumab biosimilar. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year drug retention in patients switching to adalimumab biosimilars compared with patients treated with adalimumab originator. Crude and adjusted retention rates for the adalimumab biosimilar cohort were compared with the adalimumab originator cohort with Cox proportional hazards regression using robust variance. RESULTS: A total of 348 patients were included in the adalimumab biosimilar cohort (mean [SD] age, 52.2 [13.6] years; 251 [72.1%] male) and 378 patients in the adalimumab originator cohort (mean [SD] age, 51.1 [14.1] years; 272 [72.0%] male). The 1-year drug retention rates were 92.0% (95% CI, 89.0%-94.9%) for the adalimumab biosimilar cohort and 92.1% (95% CI, 89.4%-94.8%) for the adalimumab originator cohort. Similar hazard ratios were observed between the 2 cohorts. The crude hazard ratios were 1.02 (95% CI, 0.61-1.70; P = .94) for all causes of drug discontinuation, 0.82 (95% CI, 0.39-1.73; P = .60) for insufficient effect, and 1.41 (95% CI, 0.52-3.77; P = .50) for adverse events for the adalimumab biosimilar cohort when compared with the adalimumab originator cohort. CONCLUSIONS AND RELEVANCE: In this cohort study from Denmark, a nonmedical switch from adalimumab originator to adalimumab biosimilars was not associated with drug retention.

Response to Biologics During the First Six Months of Therapy in Biologic-naïve Patients with Psoriasis Predicts Risk of Disease Flares: A Danish Nationwide Study.

Early response to treatment with biologics might be important for the stability of psoriasis and long-term outcome. The aim of this study was therefore to assess whether risk of flares and drug survival are associated with disease activity in the first 6 months of treatment of psoriasis with biologics. Biologic-naïve patients from the Danish nationwide registry, DERMBIO, were grouped based on absolute Psoriasis Area and Severity Index (PASI) during the first 6 months of treatment, as: PASI = 0, PASI > 0-≤2, PASI > 2-≤ 4, and PASI > 4. Among 1,684 patients, 746 achieved PASI= 0, 485 PASI > 0-≤2, 246 PASI > 2-≤4, and 207 PASI > 4. Longer flare-free period and drug survival were observed for patients with lower PASI in the first 6 months of treatment (adjusted hazard ratios for flares (95% confidence interval) with PASI= 0 as reference: PASI > 0-≤2 (1.35 (1.11-1.72]), PASI > 2-≤ 4 (2.32 [1.80-2.99]), and PASI > 4 (2.38 [1.80-3.15])). In conclusion, a low PASI in the first 6 months of treatment with biologics in biologic-naïve patients with psoriasis was associated with a more stable disease course, lower risk of flares, and longer drug survival.

Long-term evaluation of climatotherapy for psoriasis.

Climatotherapy (CT) is a treatment with immediate high clearance rate for chronic psoriasis, but evidence of long-term effects is scarce. Assessment of the impact of a single CT treatment on disease activity and quality of life was carried out at 4- to 6-month follow-ups. A prospective study of patients with psoriasis undergoing 4 weeks of CT in Israel describes long-term outcomes of CT. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were assessed before CT and at an average of 5 months after return. Assessment of the eligibility for CT takes place twice a year. A total of 49 patients (28/21 M/F) participated. Pretreatment PASI was 2.6 to 18.7 (mean 8.1 ± 3.8) vs control PASI 0 to 16.9 (mean 5 ± 2.8), (P < .0001). Mean ΔPASI was 3.2 (39.5% reduction). PASI 75 was achieved by 11/49 patients; 10/49 had increased PASI. The mean DLQI score was 16.1 (range 2-30); 10.6 at follow-up (range 0-28), and 33 patients achieved DLQI minimal clinically important difference (P < .0001). Age, sex, number of previous CT, and duration of observation period did not affect endpoints. CT and unmonitored self-treatment induces PASI 75 in one-fifth patients at follow-up 4 to 6 months later. Six of 10 patients report a clinically important improvement of patients' quality of life as measured by DLQI.

Patient-reported Outcomes During Treatment in Patients with Moderate-to-severe Psoriasis: A Danish Nationwide Study.

The initiation and evaluation of treatment with biologics for psoriasis is based on the Psoriasis Area Severity Index (PASI) and/or Dermatological Life Quality Index (DLQI). However, these indices do not always correlate well, and changes in the DLQI do not always follow changes in the PASI. Based on data from the Danish national registry (DERMBIO), this study investigated the correlation between changes in PASI and DLQI in a cohort of patients with moderate-to-severe psoriasis treated with biologics or apremilast using Spearman's rank correlation analyses. The correlation analysis of 1,677 patients, of whom 276 had available data after 5 years, showed weak-to-moderate correlation between PASI and DLQI during a 5-year period and between changes in PASI and DLQI: 0.58 (p < 0.0001) for baseline to 3 months and 0.42 (p < 0.0001) for 3 to 12 months. The first question on "Symptoms and feelings" made up the largest proportion of the overall DLQI. The correlation between PASI and DLQI is weak-to-moderate and varies over time. Changes in PASI correlate weak-to-moderately with changes in DLQI during the first 12 months of treatment, with symptoms being the most important factor contributing to impaired quality of life.

Drug survival of secukinumab and ixekizumab for moderate-to-severe plaque psoriasis.

BACKGROUND: Biologics targeting interleukin 17 are increasingly being used for treatment of moderate-to-severe psoriasis, but data on drug survival for these therapies remain scarce. OBJECTIVES: To investigate the drug survival of secukinumab and ixekizumab in a nationwide cohort of patients with psoriasis in Denmark. METHODS: Using DERMBIO, we examined Danish patients receiving treatment with secukinumab or ixekizumab according to the standard in-label dosing. Kaplan-Meier plots were used to present survival curves. RESULTS: In all, 368 and 62 patients received treatment with secukinumab and ixekizumab, respectively. In total, 40.7% and 12.9% of secukinumab- and ixekizumab-treated patients were bionaive. Ixekizumab-treated patients had received significantly more previous treatments. Over 12 months, 23.5% and 0.0% of bionaive secukinumab- and ixekizumab-treated patients discontinued therapy, respectively. Drug survival for bionaive and non-naive patients was lower for secukinumab than for ixekizumab. During the maximum 3 years of follow-up, secukinumab drug survival was lowest for patients who had previously been treated with 2 or more biologics, followed by patients treated with secukinumab as their second-ever biologic. LIMITATIONS: The total number of patients and follow-up time were modest. CONCLUSIONS: Drug survival was higher for ixekizumab even though secukinumab-treated patients had been treated with significantly fewer biologics before starting this drug.

High body mass index in adolescent girls precedes psoriasis hospitalization.

Psoriasis is associated with being overweight, but the temporal relationship is not known. This historical cohort study tested whether severe psoriasis resulting in hospitalization in adulthood was preceded by excess increase in age-adjusted body mass index, a known risk factor in childhood for being overweight in adulthood. The study cohort was based on the Copenhagen School Health Records Register, birth years 1930 to 1984 (309,152 schoolchildren). Cases were found through the Danish National Patient Register for the period 1977 to 2001. A total of 1074 (0.36%) of the schoolchildren were identified as having psoriasis, with at least one hospital admission. Multivariate analysis demonstrated an association between excess increase in body mass index and psoriasis in females only. Being overweight in adolescence was the main factor behind this observation. The female group showed a significant association between psoriasis and body mass index at ages 12 (p = 0.028) and 13 years (p = 0.010). This was not the case for males or for body mass index measured at ages 11 years and below.

Hidradenitis suppurativa complicating naevus comedonicus: the possible influence of mechanical stress on the development of hidradenitis suppurativa.

Naevus comedonicus is a rare, benign hamartoma consisting of grouped abnormal hair follicles and, occasionally, associated with other diseases. We describe an infant who developed hidradenitis-like lesions in an inguinal naevus comedonicus following increased mechanical stress on the region. It is speculated that the degree of strain on a hair follicle is increased when its diameter is increased, leading to wall ruptures. We hypothesise that this serendipitous observation provides a model for the way mechanical stress can account for the development of hidradenitis suppurativa in some patients.

Genetic factors in nickel allergy evaluated in a population-based female twin sample.

Environmental exposures are important for development of allergic contact dermatitis, but genetic factors have been proposed to be of additional importance for contact sensitization. Recently genetic factors were shown to be of significance for hand eczema. In this study, a sample of twins recruited on the basis of hand eczema has been evaluated with respect to influence of genetic factors on development of nickel sensitization. A total of 1076 individual twins were patch tested and underwent clinical examination, and in the final genetic statistical analysis 630 females were available, of which 146 had a positive patch test to nickel. The aggregation of nickel allergy among twin pairs was measured by the casewise concordance and the twin odds ratio. The twin odds ratio were adjusted for effects of risk factors known to be associated with nickel allergy, namely, wet work, atopic dermatitis, and self-reported hand eczema. There was a small tendency for larger odds ratio among monozygotic twins than among dizygotic twins, which was not statistically significant. As a result of the statistical analysis, it is concluded that allergic nickel contact dermatitis is mainly caused by environmental and only to a lesser degree genetic factors. The selection of twins on the basis of hand eczema may theoretically influence the prevalence of nickel allergy and concordance estimates, which should be considered before extrapolating the data to a random population-based twin sample.

Analysis of twin data ascertained through probands: the double-entry approach.

Twin pairs are sometimes included in studies because at least one of them is a proband, and conventionally the analysis of the data is based on the conditional distribution of the co twin given the proband. In the case of more than one proband in each pair, an often used "ad hoc" method of analysis is to allow each twin to act as proband as well as co twin. An example of this is the pro band wise concordance, which is used as an estimate of the case wise concordance under incomplete ascertainment. In this paper, we show that the method of double entry under a regularity condition provides consistent estimates of parameters, but that conventional standard errors as well as a correction suggested by Stevenson et al. will be wrong. Instead, we recommend the use of an easily calculated sandwich estimator. We illustrate the method with twin data from a study of the genetic component in hand eczema.

Relation between vesicular eruptions on the hands and tinea pedis, atopic dermatitis and nickel allergy.

The aetiology of vesicular eruptions on the palms and on the sides of the fingers (pompholyx) is unclear. The present study was undertaken to establish whether tinea pedis, atopic dermatitis or nickel allergy is a risk factor for development of vesicular eruptions. Three-hundred-and-ninety-eight individuals (included from an ongoing population study on hand eczema in twins) were included. A history of previous hand eczema and atopic dermatitis was taken, and a clinical examination including a patch test with nickel was performed. A test sample for tinea pedis was taken from the fourth interdigital space on the right foot. The relative risk for vesicular eruptions present in individuals with tinea pedis was 3.58 (confidence limits 1.19-10.82, p < 0.05). For individuals with atopic dermatitis, relative risk was 1.44 (confidence limits 0.34-6.07, n.s.) and for those with nickel allergy it was 0.45 (confidence limits 0.06-3.36, n.s.). A relationship between tinea pedis and vesicular eruptions on the hands was statistically confirmed in the present study. In this part of the population study material, no association with atopic dermatitis or nickel allergy was observed.