Psychometric Properties of an Arabic Pain Anxiety Symptoms Scale-20 (PASS-20) in Healthy Volunteers and Patients Attending a Physiotherapy Clinic.

PURPOSE: The aim of this study was to cross-culturally adapt the PASS-20 questionnaire for use in Libya. METHODS: Participants were 71 patients (42 women) attending the physiotherapy clinic, Ibn Sina Hospital, Sirt, Libya for management of persistent pain and 137 healthy unpaid undergraduate students (52 women) from the University of Sirt, Libya. The English PASS-20 was translated into Arabic. Patients completed the Arabic PASS-20 and the Arabic Pain Rating Scales on two occasions separated by a 14-day interval. Healthy participants completed the Arabic PASS-20 on one occasion. RESULTS: The internal consistency (ICC) for pain patient and healthy participant samples yielded a good reliability for the total score, cognitive anxiety, fear of pain, and physiological anxiety. The test-retest reliability of the Arabic PASS-20 score showed high reliability for the total score (ICC = 0.93, p < 0.001), escape/avoidance (ICC = 0.93, p < 0.001), fear of pain (ICC = 0.94, p < 0.001), and physiological anxiety subscales (ICC = 0.96, p < 0.001) and good reliability for the cognitive anxiety (ICC = 0.85, p < 0.001). Inspection of the Promax rotation showed that each factor comprised of five items were consistent with the theoretical constructs of the original PASS-20 subscales. CONCLUSION: The Arabic PASS-20 retained internal consistency and reliability with the original English version and can be used to measure pain anxiety symptoms in both pain and healthy individual samples in Libya

Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for patients with moderate-to-severe psoriasis: a cohort study from BADBIR

Background Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited. Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis. Methods Data from The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective, multi-centre pharmacovigilance register of patients with moderate-to-severe psoriasis receiving biologic and/or conventional systemic therapies, were analysed. Eligible patients were ≥16 years of age receiving a first course of acitretin, ciclosporin, FAEs or methotrexate between 2007 and 2021 with ≥6 months’ follow-up. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥4 weeks after treatment start date until stop date. To identify baseline clinical variables associated with treatment effectiveness, we used multivariable logistic regression models estimating the adjusted odds ratio (aOR) of achieving aPASI ≤2. To describe drug persistence associated with ineffectiveness, occurrence of adverse events or other reasons of discontinuation, survival estimates with 95% confidence interval (CI) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis: 1023 (19%) on acitretin, 1401 (26%) ciclosporin, 347 (6%) FAEs and 2659 (49%) methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower with acitretin 118 (21%) compared with those on ciclosporin 233 (34%), FAEs 43 (30%) and methotrexate 372 (32%). Factors associated with ineffectiveness included prior experience to previous non-biologic systemic therapies (acitretin) [(aOR, (95% CI) 0.64 (0.42, 0.96)], male sex (methotrexate) 0.58 (0.46, 0.74), co-morbidities 0.70 (0.51, 0.97) and alcohol consumption (≤14 units per week) (ciclosporin) 0.70 (0.50, 0.98). Persistence associated with all reasons of discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [(Survival estimate (95% CI), 46.1 (44.0, 48.3), 31.9 (29.4, 34.7), 30.0 (27.5, 32.4) and 35.0 (29.9, 40.9)], respectively. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous non-biologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

IMPORTANCE: Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.OBJECTIVE: To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.EXPOSURES: Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.MAIN OUTCOMES AND MEASURES: Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models.RESULTS: Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).CONCLUSIONS AND RELEVANCE: In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.</p

Discontinuation of anti-TNF-alpha treatment due to blood test abnormalities and cost-effectiveness of alternate blood monitoring strategies

Background: There is no evidence base supporting the use of six-monthly monitoring blood tests for the early detection of liver, blood, and renal toxicity during established anti-TNF-alpha treatment. Objectives: To evaluate the incidence and risk factors of anti-TNF-alpha treatment cessation due to liver, blood, and renal side-effects and, to estimate the cost effectiveness of alternate intervals between monitoring blood tests.Methods: A secondary-care based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register were used. Patients with at-least moderate psoriasis prescribed their first anti-TNF-alpha treatment were included. Treatment discontinuation due to monitoring blood test abnormality was the primary-outcome.Patients were followed-up from treatment start to the earliest of outcome, drug discontinuation, death, five years, or 31/07/2021. The incidence rate and 95% confidence intervals (CIs) of anti-TNF-alpha discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk-factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with lengthening the time between monitoring blood tests during anti-TNF-alpha treatment.Results: The cohort included 8,819 participants (3,710 (42.1%) female, mean age (standard deviation) 44.76 (13.20) years) that contributed 25,058 person-years of follow-up and experienced 125 treatment discontinuations due to monitoring blood test abnormality at an incidence rate (95%CI) of 5.85 (4.91-6.97)/1,000 person-years. Of these, 64, and 61 discontinuations occurred within the first year, and after the first year of treatment start, at an incidence rate (95% CI) of 8.62 (6.74-11.01) and 3.44 (2.67-4.42)/1000 person-years respectively. Increasing age in years, diabetes, and liver disease associated with anti-TNF-alpha discontinuation with monitoring blood test abnormality with adjusted Hazard Ratio (95%CI) of 1.02 (1.01-1.04), 1.68 (1.00-2.81), and 2.27 (1.26-4.07) respectively. Assuming a threshold of £20,000 per QALY gained, no monitoring was most cost-effective but all extended periods were cost-effective compared to three monthly or six-monthly monitoring.Conclusion: Anti-TNF-alpha drugs were uncommonly discontinued due to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood-tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs

Effectiveness and survival of methotrexate versus adalimumab in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

BackgroundMost information on the comparative effectiveness and survival of methotrexate (MTX) and adalimumab (ADA) in the treatment of psoriasis is from randomized control trials and may not translate to the everyday clinical setting.ObjectivesTo determine the real-world effectiveness and survival of MTX and ADA in patients with moderate-to-severe psoriasis registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).MethodsEligible patients were registered in BADBIR, ≥ 16 years of age and receiving a first course of MTX or ADA between September 2007 and December 2021, with ≥ 6 months of follow-up. Effectiveness was defined as achieving an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 reported ≥ 13 weeks after the treatment start date until the stop date. The average treatment effect (ATE) was estimated using inverse probability of treatment weighting with propensity score, including baseline covariates. ATE results were presented as risk ratios (RR). A flexible parametric model was used to estimate adjusted standardized average survival, defined as treatment discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs) at 6, 12 and 24 months. Restricted mean survival time (RMST) at 2 years of treatment exposure was calculated.ResultsIn total, 6575 patients (median age 44 years; 44% female) were analysed; 2659 (40.4%) were prescribed MTX and 3916 (59.5%) ADA. The proportion of patients achieving PASI ≤ 2 was higher in the ADA cohort (77.4%) than in the MTX cohort (37.4%). ADA was more effective than MTX [RR 2.20, 95% confidence interval (CI) 1.98–2.45]. Overall survival associated with ineffectiveness or AEs was lower in the MTX cohort than in the ADA cohort at 6 months [survival estimate 69.7 (95% CI 67.9–71.5) vs. 90.6 (95% CI 89.8–91.4)], 1 year [survival estimate 52.5 (95% CI 50.4–54.8) vs. 80.6 (95% CI 79.5–81.8)] and 2 years [survival estimate 34.8 (95% CI 32.5–37.2) vs. 68.6 (95% CI 67.2–70.0)]. The difference in RMST (years) overall, or when stratified by ineffectiveness and AEs, was 0.53 (95% CI 0.49–0.58), 0.37 (95% CI 0.33–0.42) and 0.29 (95% CI 0.25–0.33), respectively.ConclusionsPatients on ADA were twice as likely to be clear or nearly clear of psoriasis and were less likely to discontinue their medication than patients on MTX. Findings from this real-world cohort provide important information to aid clinicians managing patients with psoriasis

The association of age at psoriasis onset and HLA-C*06:02 with biologic survival in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

Background Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures. Objectives To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. Methods Data from patients in the UK and the Republic of Ireland registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2022 on first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months’ follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥50 years at treatment initiation were classified into early onset psoriasis (EOP; presenting ≤40 years of age) and late onset (LOP; presenting &amp;gt; 40 years of age); BADBIR patients with available information in BSTOP were categorised into HLA-C*06:02-ve and HLA-C*06:02+ve. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates. Results Final analytical cohorts included 4250 patients (2929 [69%] EOP vs. 1321 [31%] LOP) and 3094 patients (1603 [52%] HLA-C*06:02+ve vs. 1491 [48%] HLA-C*06:02-ve). There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, HLA-C*06:02+ve compared with HLA-C*06:02-ve patients were less likely to discontinue ustekinumab associated with ineffectiveness 0.56 [0.42, 0.75]. Conclusions HLA-C*06:02 but not age at psoriasis onset is a predictive biomarker for biologic survival in psoriasis patients. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage psoriasis patients

Characteristics of “Super-Responders” and “Super-Non-Responders” to First Biologic Monotherapy for Psoriasis: A Nested Case-control Study

It is unknown why some psoriasis patients experience long-term effectiveness with their first biologic monotherapy. Our aim was to compare the baseline demographic, disease, genotypic, clinical and lifestyle characteristics of patients with psoriasis registered to BADBIR and the aligned BSTOP study and designated as super responders (SRs), defined as patients on their first biologic with more than 5 years continuous biologic monotherapy or SNRs, defined as patients on their first biologic who had discontinued at least two biologics in their first year of treatment, to biologic therapy. Female sex, shorter study follow-up, higher DLQI, high frequency of adalimumab, less frequency of ustekinumab at registration, and higher number of comorbidities were associated with SNRs compared with SRs