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  • 1
    In: British Journal of Dermatology, Oxford University Press (OUP), Vol. 190, No. 5 ( 2024-04-17), p. 689-700
    Abstract: 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 registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a 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 in patients ≤ 40 years of age) and late-onset psoriasis (LOP) (presenting in patients & gt; 40 years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02− or HLA-C*06:02 + . 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 in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02− (48%)] . There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02−, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42–0.75). Conclusions HLA-C*06:02, but not age at psoriasis onset, is a predictive biomarker for biologic survival in patients with psoriasis. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage patients with psoriasis.
    Type of Medium: Online Resource
    ISSN: 0007-0963 , 1365-2133
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 2
    In: British Journal of Dermatology, Oxford University Press (OUP), Vol. 188, No. 5 ( 2023-04-20), p. 618-627
    Abstract: 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, multicentre 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 date of cessation. 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 for discontinuation, survival estimates with 95% confidence intervals (CIs) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis. Overall, 1023 (19%) patients were receiving acitretin, 1401 (26%) patients were on ciclosporin, 347 (6%) patients were on FAEs, and 2659 (49%) patients were receiving methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower for those treated with acitretin [n = 118 (21%)] compared with those receiving ciclosporin [n = 233 (34%)] , FAEs [n = 43 (29%)] and methotrexate [n = 372 (32%)] . Factors associated with ineffectiveness included prior experience to previous nonbiologic systemic therapies (acitretin) (aOR 0.64, 95% CI 0.42–0.96), male sex (methotrexate) (aOR 0.58, 95% CI 0.46–0.74), comorbidities (aOR 0.70, 95% CI 0.51–0.97) and alcohol consumption (≤ 14 units per week) (ciclosporin) (aOR 0.70, 95% CI 0.50–0.98). Persistence associated with all reasons for discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [survival estimate 46.1 (95% CI 44.0–48.3), 31.9 (95% CI 29.4–34.7), 30.0 (95% CI 27.5–32.4) and 35.0 (95% CI 29.9–40.9), respectively]. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous nonbiologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness.
    Type of Medium: Online Resource
    ISSN: 0007-0963 , 1365-2133
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 3
    In: British Journal of Dermatology, Oxford University Press (OUP), Vol. 190, No. 3 ( 2024-02-16), p. 441-444
    Abstract: It is unknown why some patients with psoriasis 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 in the British Association of Dermatologists Biologics and Immunomodulators Register and the aligned Biomarkers and Stratification to Optimise outcomes in Psoriasis study who were designated as ‘super responders’ (SRs), defined as patients on their first biologic with more than 5 years continuous biologic monotherapy, or ‘super nonresponders’ (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 Dermatology Life Quality Index, high frequency of adalimumab, less frequency of ustekinumab at registration, and higher number of comorbidities were associated with SNRs compared with SRs.
    Type of Medium: Online Resource
    ISSN: 0007-0963 , 1365-2133
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 4
    In: British Journal of Dermatology, Oxford University Press (OUP), Vol. 189, No. 3 ( 2023-08-24), p. 271-278
    Abstract: Most 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. Objectives To 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). Methods Eligible 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. Results In 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. Conclusions Patients 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.
    Type of Medium: Online Resource
    ISSN: 0007-0963 , 1365-2133
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 5
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 116, No. 1 ( 2020-01-01), p. 149-157
    Abstract: To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments. Methods and results National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge includ ing [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), β-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4–8.5) vs. 6.7 (6.5–6.9)] and NSTEMI [6.8 (6.4–7.2) vs. 4.9 (4.7–5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5–3.3) vs. 2.3 (2.2–2.5)] and [21.4 (20.0–22.8) vs. 18.3 (17.6–19.0)], but was similar for STEMI [0.7 (0.4–1.0) vs. 0.9 (0.7–1.0)] and [8.4 (6.7–10.1) vs. 8.3 (7.5–9.1)]. Conclusion Short-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 6
    Online Resource
    Online Resource
    Informa UK Limited ; 2012
    In:  Pain Management Vol. 2, No. 4 ( 2012-07), p. 315-317
    In: Pain Management, Informa UK Limited, Vol. 2, No. 4 ( 2012-07), p. 315-317
    Type of Medium: Online Resource
    ISSN: 1758-1869 , 1758-1877
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2012
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  • 7
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. 4 ( 2021-04), p. 502-508
    Abstract: Osteoarthritis (OA) structural status is imperfectly classified using radiographic assessment. Statistical shape modelling (SSM), a form of machine-learning, provides precise quantification of a characteristic 3D OA bone shape. We aimed to determine the benefits of this novel measure of OA status for assessing risks of clinically important outcomes. Methods The study used 4796 individuals from the Osteoarthritis Initiative cohort. SSM-derived femur bone shape (B-score) was measured from all 9433 baseline knee MRIs. We examined the relationship between B-score, radiographic Kellgren-Lawrence grade (KLG) and current and future pain and function as well as total knee replacement (TKR) up to 8 years. Results B-score repeatability supported 40 discrete grades. KLG and B-score were both associated with risk of current and future pain, functional limitation and TKR; logistic regression curves were similar. However, each KLG included a wide range of B-scores. For example, for KLG3, risk of pain was 34.4 (95% CI 31.7 to 37.0)%, but B-scores within KLG3 knees ranged from 0 to 6; for B-score 0, risk was 17.0 (16.1 to 17.9)% while for B-score 6, it was 52.1 (48.8 to 55.4)%. For TKR, KLG3 risk was 15.3 (13.3 to 17.3)%; while B-score 0 had negligible risk, B-score 6 risk was 35.6 (31.8 to 39.6)%. Age, sex and body mass index had negligible effects on association between B-score and symptoms. Conclusions B-score provides reader-independent quantification using a single time-point, providing unambiguous OA status with defined clinical risks across the whole range of disease including pre-radiographic OA. B-score heralds a step-change in OA stratification for interventions and improved personalised assessment, analogous to the T-score in osteoporosis.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  International Journal of Behavioral Medicine Vol. 24, No. 3 ( 2017-6), p. 457-472
    In: International Journal of Behavioral Medicine, Springer Science and Business Media LLC, Vol. 24, No. 3 ( 2017-6), p. 457-472
    Type of Medium: Online Resource
    ISSN: 1070-5503 , 1532-7558
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
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    detail.hit.zdb_id: 2027575-4
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  • 9
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. 4 ( 2022-04), p. 490-495
    Abstract: To characterise the impact of dactylitis in disease-modifying antirheumatic drug (DMARD)-naive early psoriatic arthritis (PsA). Methods Patients with early PsA meeting the classification criteria for PsA (CASPAR) were recruited. Clinical outcomes were recorded, and ultrasonography was conducted to assess grey scale (GS) and power Doppler (PD) synovitis, periarticular cortical bone erosions and enthesitis. The cohort was dichotomised by the presence or absence of dactylitis. Results Of 177 patients with PsA, those with dactylitis (dactylitic PsA (81/177, 46%)) had higher tender joint count (p 〈 0.01), swollen joint count (SJC) (p 〈 0.001) and C reactive protein (CRP) (p 〈 0.01) than non-dactylitic PsA. Dactylitis was more prevalent in toes (146/214 (68.2%)) than fingers (68/214 (31.8%)); ‘hot’ dactylitis was more prevalent than ‘cold’ (83.6% vs 16.4%). Ultrasound (US) synovitis and erosions were significantly more prevalent in dactylitic PsA (p 〈 0.001 and p 〈 0.001, respectively). Exclusion of dactylitis in dactylitic PsA confirmed significantly greater SJC (3 vs 1, p=0.002), US synovitis (GS ≥2: 20.6% vs 16.1%, p 〈 0.001, or PD ≥1: 5.1% vs 3.3%, p 〈 0.001) and erosions (1.1% vs 0.5% joints, p=0.008; 26.1% vs 12.8% patients, p=0.035%) than non-dactylitic PsA. Synovitis (GS ≥2 and/or PD ≥1) occurred in 53.7% of dactylitis. No substantial differences were observed for US enthesitis. Conclusion Dactylitis signifies a more severe disease phenotype independently associated with an increased disease burden with greater SJC, CRP, US-detected synovitis and bone erosions in DMARD-naive early PsA and may be a useful discriminator for early risk stratification.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1481557-6
    detail.hit.zdb_id: 7090-7
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  • 10
    In: Rheumatology Advances in Practice, Oxford University Press (OUP), Vol. 5, No. 3 ( 2021-08-31)
    Abstract: To evaluate the relationship between clinical examination/US synovitis in DMARD-naïve early PsA. Methods Eligible patients underwent matched clinical/US 44-joint assessment for tender and/or swollen joints (TJ/SJ) and US synovitis [grey scale (GS) ≥ 2 or power Doppler (PD) ≥ 1]. Statistical agreement between TJ/SJ, GS ≥ 2 and PD ≥ 1 was calculated by prevalence-adjusted and bias-adjusted κ (PABAK). To derive probabilities of GS ≥ 2/PD ≥ 1, mixed-effects logistic regression-modelled odds of US synovitis in TJ/SJ were conducted. Results In 155 patients, 5616 joints underwent clinical/US examination. Of these joints, 1039 of 5616 (18.5%) were tender, 550 of 5616 (9.8%) were swollen, 1144 of 5616 (20.4%) had GS ≥ 2, and 292 of 5616 (5.2%) had PD ≥ 1. GS ≥ 2 was most prevalent in concomitantly tender and swollen joints [205 of 462 (44%)], followed by swollen non-tender joints [32 of 88 (36.4%)] , tender non-swollen joints [148 of 577 (25.7%)] and non-tender non-swollen joints (subclinical synovitis) [759 of 4489 (16.9%)] . Agreement between SJ/PD ≥ 1 was high at the individual joint level (82.6–96.3%, PABAK 0.65–0.93) and for total joints combined (89.9%, PABAK 0.80). SJ/GS ≥ 2 agreement was greater than between TJ/GS ≥ 2 [73.5–92.6% vs 51.0–87.4% (PABAK 0.47–0.85 vs PABAK 0.35–0.75), respectively]. Swelling was independently associated with higher odds of GS ≥ 2 [odds ratio (OR) (95% CI); 4.37 (2.62, 7.29); P & lt; 0.001] but not tenderness [OR = 1.33 (0.87, 2.06); P = 0.192] . Swelling [OR = 8.78 (3.92, 19.66); P & lt; 0.001] or tenderness [OR = 3.38 (1.53, 7.50); P = 0.003] was independently associated with higher odds of PD ≥ 1. Conclusion Synovitis (GS ≥ 2 and/or PD ≥ 1) was more likely in swollen joints than in tender joints in DMARD-naïve, early PsA. Agreement indicated that swollen joints were the better proxy for synovitis, adding to greater understanding between clinical and US assessments.
    Type of Medium: Online Resource
    ISSN: 2514-1775
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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