Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

Sensitivity to Change (Responsiveness) and Minimal Important Differences of the LupusQoL in patients with Systemic Lupus Erythematosus

Objective: The LupusQoL is a reliable and valid health-related quality of life (HRQoL) measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MID) for the eight LupusQoL domains. Methods: Patients experiencing a flare were recruited from nine UK centres. At each of the ten monthly visits, HRQoL (LupusQoL, SF-36), global rating of change (GRC) and disease activity (DA) using the BILAG-2004 index were assessed. The responsiveness of the LupusQoL and the SF-36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and, secondly, with changes in physician-reported DA. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. Results: 101 patients were recruited. For all LupusQoL domains, mean HRQoL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF-36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF-36 was observed with a decrease in DA but when DA worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from -2.4 to -8.7 and for improvement, 3.5 to 7.3; for the SF-36, -2.0 to -11.1, and 2.8 to 10.9 respectively. Conclusion: All LupusQoL domains are sensitive to change with patient-reported deterioration or improvement in health status. For DA, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease-specific domains, important to them, not captured by the SF-36

Persistence and Effectiveness of Non-Biologic Systemic Therapies for Moderate-Severe Psoriasis in Adults: a Systematic Review

BACKGROUND: The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized. OBJECTIVES: To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ≥ 3 months. METHODS: MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771. RESULTS: Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥ 75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA. CONCLUSIONS: The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

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

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy

BACKGROUND: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. OBJECTIVES: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. METHODS: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C-statistic, the calibration slope and the calibration in the large. RESULTS: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism-corrected C-statistic of 0·64 [95% confidence interval (CI) 0·60-0·69], calibration in the large of 0·02 (95% CI -0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70-1·07), while external validation performance was poor, with C-statistic 0·52 (95% CI 0·42-0·62), calibration in the large 0·06 (95% CI -0·25 to 0·37) and calibration slope 0·36 (95% CI -0·24 to 0·97). CONCLUSIONS: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision-making process

Risks of basal cell and squamous cell carcinoma in psoriasis patients after treatment with biologic vs non‐biologic systemic therapies

'No abstract

Intentional and unintentional medication non-adherence in psoriasis: The role of patients’ medication beliefs and habit strength

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

The development and validation of a disease-specific instrument to measure quality of life in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. In the evaluation of patients with SLE it is important to measure not only disease activity and damage but also the impact of the disease on their health related quality of life (HRQoL). Disease-specific HRQoL measures are considered to be more relevant and sensitive to change. As none were currently available, this present work was conducted to develop and validate a patient-derived measure, the Lupus Quality of Life (LupusQoL) Questionnaire and to use it to describe HRQoL in a group of patients. Several stages of development led to the validation of the questionnaire. The generation of items was informed by: existing HRQoL literature; other FIRQoL measures; consultation with the rheumatology multi-disciplinary team; and patient interviews (n=30). From this, a measure comprising 67 items was generated. Twenty patients completed this initial version providing critical feedback regarding face validity and structure, content of the items and response scales, leading to further revision of the LupusQoL. This revised version of the LupusQoL (63 items) was completed by 322 patients. Principal components analysis and Cronbach alpha coefficients highlighted eight domains. The LupusQoL was further revised (42 items) based on factor analysis, clinical decision and patient feedback. Principal components analysis was performed on the data from the second version of the LupusQoL, completed by 213 patients. This confirmed the factor structure of the LupusQoL. The final measure contains 34 items comprising eight domains: physical functioning, pain, emotional functioning, fatigue, body image, intimate relationships, planning and burden to others. Cronbach alpha coefficients (all values > 0.8) and item to domain correlations showed good internal consistency of the subscales. Test-retest reliability and concurrent validity have also shown that the instrument is robust. For all domains except fatigue those with no current activity and/or only mild activity in any systems reported a better HRQoL than (a) those with moderate activity in any systems and (b) those with severe active disease in any systems (p'c0.05). Patients with no damage reported a better HRQoL than those with damage for physical health, pain, planning, intimate relationships and burden to others (p<O.O5). The LupusQoL is a valid and reliable lupus-specific HRQoL measure for adults with SLE