Drug survival reflects a drug’s effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British ...Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09–1.37), being a current smoker (HR 1.19; 95% CI: 1.03–1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00–1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71–0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45–1.84) or infliximab (HR 1.56; 95% CI: 1.16–2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37–0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.
Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk ...of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown.
To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials.
An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only.
(1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug.
The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 9%; ustekinumab, 201 12%) and nonchronic plaque psoriasis (adalimumab, 157 4%). Patients categorized as ineligible (etanercept, 367 24%; adalimumab, 282 7%; ustekinumab, 394 24%) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories.
Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.
Outcomes in systemic lupus erythematosus (SLE) can be described in three domains: disease activity, accumulated damage and health-related quality of life (HRQoL). Over the past decade, our ...understanding and perception of SLE have changed considerably. Gastrointestinal and ophthalmic manifestations have increasingly been recognised, and they are associated with significant morbidity and mortality. Furthermore, it has been realised that there is a deficiency in using generic scales (such as the short form-36 (SF-36)) to assess HRQoL in patients with SLE as they fail to identify issues that are important to patients. As a result, SLE-specific measures of HRQoL have been developed recently. This article looks at the recent updates and changes in the standardised assessment of disease activity and HRQoL in SLE.
Abstract Psoriasis is associated with poor mental health, high prevalence of depression and reduced quality of life. However, suicide risk in this group is unclear. Previous meta-analyses have ...provided conflicting results regarding risk of suicidality outcomes, including suicidal thoughts and attempts and suicide. Existing literature has not investigated patients with clinically confirmed moderate-to-severe disease. Our aims were to investigate (i) the risk of suicide among patients with moderate-to-severe psoriasis compared with the general population and (ii) whether psychiatric comorbidity or history of suicidality increases suicidality risk in patients with psoriasis. We further estimated the incidence of suicidal and self-injurious behaviours in patients. We analysed suicidality outcomes from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). For controls, we used mortality and suicide data from the general population Office for National Statistics (ONS). Data were collected before the COVID-19 lockdowns. The BADBIR cutoff was February 2020 and ONS data were 2019 entries. There were nine suicides in BADBIR. The incidence rate of suicide was 12.5 per 100 000 person-years 95% confidence interval (CI) 6.53–24.1 in BADBIR vs. 11.0 per 100 000 person-years (95% CI 10.7–11.3) in the general population in England and Wales. The incidence rate for the combined event of suicidal or self-injurious behaviour was 186 per 100 000 person-years for all patients with moderate-to-severe psoriasis (95% CI 157–221). History of psychiatric comorbidity or past suicidality significantly increased the risk for all suicidality outcomes apart from suicide, including suicide attempts and suicidal ideation, as well as self-harm behaviours. Suicide incidence was higher in patients with past psychiatric history than in those without; however, the difference was not statistically significant (23.0 per 100 000 person-years, 95% CI 8.62–61.2; vs. 9.20 per 100 000 person-years, 95% CI 3.83–22.1). In BADBIR, we could not find an increased suicide risk among patients with moderate-to-severe psoriasis compared with the general population. Further research is needed to replicate this result. Our findings highlight an increased overall suicidal and self-harm burden in patients with psychiatric comorbidities. Also, given the high prevalence of depression and anxiety in people with psoriasis, there is a need for mental health monitoring in these patients. Clinicians should ask patients openly about past and present suicidal thoughts or behaviour to ensure early intervention. BADBRL is a registered company within the BAD and funds the BADBIR study. BADBIR is coordinated by the University of Manchester as research sponsor. BADBRL receives income from AbbVie, Almirall, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen Cilag, LEO Pharma, Novartis, Samsung Bioepis and UCB for providing pharmacovigilance services. All decisions concerning analysis, interpretation and publication are made independently of any industry contribution.
Drug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently ...(effect modifiers) may inform the decision to choose between biologics.
To assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival.
We conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021.
Adalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab.
We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety.
A total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab.
The results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.
Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection ...could improve patient outcomes and treatment cost-effectiveness.
We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti–TNF-α) and ustekinumab (anti–IL-12/23).
This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables.
HLA-C*06:02–negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio OR, 2.95; P = 5.85 × 10−7), and the difference was greater in HLA-C*06:02–negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10−5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10−4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1.
This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.
Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the ...risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74–79%), falling to 58% (55–61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24–2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33–0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50–4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis.
Summary
Background
Biologic therapies have revolutionized the treatment of moderate‐to‐severe psoriasis. However, for reasons largely unknown, many patients do not respond or lose response to these ...drugs.
Objectives
To evaluate demographic, social and clinical factors that could be used to predict effectiveness and stratify response to biologic therapies in psoriasis.
Methods
Using a multicentre, observational, prospective pharmacovigilance study (BADBIR), we identified biologic‐naive patients starting biologics with outcome data at 6 (n = 3079) and 12 (n = 3110) months. Associations between 31 putative predictors and outcomes were investigated in univariate and multivariable regression analyses. Potential stratifiers of treatment response were investigated with statistical interactions.
Results
Eight factors associated with reduced odds of achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) at 6 months were identified (described as odds ratio and 95% confidence interval): demographic (female sex, 0·78, 0·66–0·93); social (unemployment, 0·67, 0·45–0·99); unemployment due to ill health (0·62, 0·48–0·82); ex‐ and current smoking (0·81, 0·66–0·99 and 0·79, 0·63–0·99, respectively); clinical factors (high weight, 0·99, 0·99–0·99); psoriasis of the palms and/or soles (0·75, 0·61–0·91); and presence of small plaques only compared with small and large plaques (0·78, 0·62–0·96). White ethnicity (1·48, 1·12–1·97) and higher baseline PASI (1·04, 1·03–1·04) were associated with increased odds of achieving PASI 90. The findings were largely consistent at 12 months. There was little evidence for predictors of differential treatment response.
Conclusions
Psoriasis phenotype and potentially modifiable factors are associated with poor outcomes with biologics, underscoring the need for lifestyle management. Effect sizes suggest that these factors alone cannot inform treatment selection.
What's already known about this topic?
Biologic therapy used in the treatment of moderate‐to‐severe psoriasis differs in its effectiveness across patients.
Previous research has indicated that patients with a higher body mass index, who smoke or who have smoked, and with a lower baseline Psoriasis Area and Severity Index (PASI) are less likely to have a good outcome with biologic therapy for the treatment of moderate‐to‐severe psoriasis.
What does this study add?
This large‐scale study in a real‐world setting confirms that weight, smoking status and baseline PASI are associated with effectiveness of biologic therapy.
There is evidence that non‐white ethnicity, female sex, unemployment, psoriasis of the palms and soles and the presence of small chronic plaques are associated with poor outcomes with biologics.
There is some evidence that men have a comparatively worse response to etanercept, relative to adalimumab, than women. Otherwise, most factors do not appear to be predictors of differential treatment response.
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Medication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for ...psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable. Eight hundred and eleven patients enrolled in the British Association of Dermatologists Biologic Interventions Register were included. Six hundred and seventeen patients were using a self-administered systemic therapy; 22.4% were classified as “non-adherent” (12% intentionally and 10.9% unintentionally). Patients using an oral conventional systemic agent were more likely to be non-adherent compared to those using etanercept or adalimumab (29.2% vs. 16.4%; P ≤ 0.001). Latent profile analysis supported a three-group model; all groups held strong beliefs about their need for systemic therapy but differed in levels of medication concerns. Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group 2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence interval = 1.16−4.47) and weaker medication-taking routine or habit strength was associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence interval = 0.89−0.96). Medication beliefs and habit strength are modifiable targets for strategies to improve adherence in psoriasis.
Abstract
Objective
SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients.
Methods
SLE patients with one or more ‘A’ ...or ‘B’ BILAG-2004 systems meeting flare criteria (‘new’ or ‘worse’ items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any ‘A’ irrespective of number of ‘B’ flares), moderate (two or more ‘B’ without any ‘A’ flares) and mild (one ‘B’).
Results
Of the 100 patients, 94% were female, 61% White Caucasians, mean age (s.d.) was 40.7 years (12.7) and mean disease duration (s.d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any ‘A’ or ‘B’ flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system.
Conclusion
. In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate–severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design.
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