| 1. |
|
|
| 2. |
- Kravvariti, Evrydiki, et al.
(författare)
-
Meta-analysis of placebo-arm dropouts in osteoporosis randomized-controlled trials and implications for nocebo-associated discontinuation of anti-osteoporotic drugs in clinical practice
- 2023
-
Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 34:3, s. 585-598
-
Tidskriftsartikel (refereegranskat)abstract
- Summary: Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice.Purpose: Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials.Methods: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843).Results: Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals >= 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts.Conclusion: Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted.
|
|
| 3. |
|
|
| 4. |
- Terpos, E., et al.
(författare)
-
Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis
- 2011
-
Ingår i: Clinical and Experimental Rheumatology. - Pisa, Italy : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 29:6, s. 921-925
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: A critical role of interleukin-6 (IL-6) in bone homeostasis has been suggested in experimental studies. We examined whether inhibition of IL-6 receptor in patients with rheumatoid arthritis (RA) results in early alterations of circulating markers of bone remodelling.Methods: Circulating levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), Wnt signalling pathway inhibitors Dickkopf-1 (Dkk-1) and sclerostin, markers of bone resorption (C-terminal cross-linking telopeptide of collagen type-I (CTX), tartrate-resistant acid phosphatase isoform-5b) and bone formation (bone-specific alkaline-phosphatase, osteocalcin) were examined in 22 women with active RA before and after two monthly infusions of tocilizumab (8mg/kg each); 'healthy', non-osteopenic, 1:1 age-matched women served as controls.Results: At baseline, osteoprotegerin/RANKL ratio in patients was lower than controls by 5-fold; circulating osteoprotegerin correlated negatively with corresponding 28-joint-count disease activity scores and circulating RANKL correlated positively with C-reactive protein. Also, Dkk-1, sclerostin, CTX and osteocalcin levels were higher in RA than controls. After two months, osteoprotegerin/RANKL ratio increased, Dkk-1 decreased and sclerostin increased comparing to baseline; other markers did not change significantly. Increases of osteoprotegerin/RANKL ratio were more prominent in 10 patients who achieved remission or low disease activity after tocilizumab than in 12 patients who did not. In contrast, the significant alterations of both Wnt inhibitors were comparable between these patient subgroups.Conclusions: Anti-IL-6 therapy induced suppression of the inflammatory response affects rapidly the disrupted bone homeostasis in active RA. An additional, possibly specific, effect of IL-6 receptor inhibition on bone remodelling in humans should be further examined.
|
|
| 5. |
- Bratis, Konstantinos, et al.
(författare)
-
CMR feature tracking in cardiac asymptomatic systemic sclerosis : Clinical implications
- 2019
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:8, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background.METHODS: Fifty-four cardiac asymptomatic SSc patients (44 females, 56±13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age- matched healthy controls (17 females; 54±19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used.RESULTS: Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62±6% vs. 59±5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p<0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls.CONCLUSIONS: In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients' phenotypic and autoimmune features.
|
|
| 6. |
- Crowson, Cynthia S., et al.
(författare)
-
Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis
- 2018
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:1, s. 48-54
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. Methods: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. Results: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). Conclusions: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.
|
|
| 7. |
- Fragoulis, GE, et al.
(författare)
-
SIMILAR CARDIOVASCULAR COMORBIDITY AND HIGHER DEPRESSION RATES IN PSORIATIC ARTHRITIS COMPARED TO AGE- AND SEX-MATCHED RHEUMATOID ARTHRITIS AND DIABETES MELLITUS PATIENTS
- 2020
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 758-759
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Comorbidities are frequent in psoriatic arthritis (PsA) but it is not known how they differ from other high comorbidity burden diseases like rheumatoid arthritis (RA) and diabetes mellitus (DM).Objectives:To compare the prevalence of comorbidities in PsA vs. RA and DM patients.Methods:215 PsA patients were age/gender-matched with 215 RA and 215 DM patients from two tertiary hospitals. Prevalence of comorbidities (hypertension, current smoking, hyperlipidemia, obesity (BMI≥30), coronary disease [CD], stroke, MACE [combined CD and stroke], depression, osteoporosis, history of malignancies) were compared across the three groups. Within PsA group, associations between comorbidities and demographic and clinical features (e.g entheitis), including PsA phenotypes (RA-like vs oligoarthritis pattern and Axial-involvment vs Non-Axial-involvement) were assessed.Results:Hyperlipidaemia, obesity and depression were more frequent in PsA vs. RA. Depression and osteoporosis were more common in PsA vs DM. In contrast, hypertension was more frequent in DM. All other comorbidities, including frequency of stroke, CD and major adverse cardiovascular events did not differ between groups. Results remain unchanged after adjustments (Table 1).Table 1.Comparison of comorbidities between psoriatic arthritis (PsA), rheumatoid (RA) arthritis and Diabetes mellitus (DM) patients. OR: odds ratio, MACE: major adverse cardiovascular events. CI: Confidence IntervalsPsA vs RAPsA vs DMComorbidityPsAn=215n (%)RAn=215n (%)DMN=215n (%)Crude OR(95% CI)Adjusted OR(95% CI)Crude OR(95% CI)Adjusted OR(95% CI)Smoking76 (35.4)62 (28.8)85 (39.5)1.35(0.90-2.03)0.84(0.57-1.24)Obesity50 (29.4)24 (12.8)79 (36.7)2.83(1.65-4.86)0.72(0.47-1.10)Hyperlipidemia101 (47.0)67 (31.2)101 (47.0)1.96(1.32-2.90)-1-Hypertension62 (28.8)51 (23.8)97 (45.1)1.30(0.84-1.99)-0.49(0.33-0.74)-Coronary disease10 (4.7)10 (4.7)16 (7.4)1(0.41-2.45)0.97(0.34-2.79)*0.61(0.27-1.37)0.66(0.23-1.91)*Stroke8 (3.7)2 (0.9)7 (3.3)4.12(0.86-19.6)3.74(0.73-19.3)*1.15(0.41-3.22)1.20(0.35-4.12)*MACE12 (5.6)12 (5.6)22 (10.2)1(0.44-2.28)0.94(0.36-2.46)*0.52(0.25-1.08)0.42(0.16-1.10)*Osteoporosis9 (5.5)24 (11.2)2 (0.9)0.46(0.21-1.03)0.67(0.28-1.64)**6.22(1.33-29.2)-Depression42 (19.5)15 (7.0)12 (5.6)3.24(1.74-6.04)3.02(1.57-5.81)***4.11(2.10-8.05)4.85(2.37-9.93)***Malignancy12 (5.6)7 (3.3)-1.76(0.68-4.55)1.60(0.60-4.26)****--* adjusted for age, gender, smoking, hypertension, dyslipidemia, body mass index, ** adjusted for steroids, *** adjusted for age, gender, disease duration, smoking, **** adjusted for age, disease durationWithin PsA group, depression was associated with female gender (p=0.02), older age (p=0.03), higher disease duration (p=0.04) and current smoking (p=0.04). MACEs in PsA, were associated with male gender (p=0.03), older age (p=0.0002), dyslipidaemia (p=0.003) and hypertension (p<0.0001). No differences were found between different phenotypes of PsA.Conclusion:PsA patients had higher BMI and hyperlipidaemia compared to RA but not to DM. MACE is comparable between PsA and RA or DM, while depression is more common in PsA. Taking into account certain risk factors, screening for and management of comorbidities in PsA is important in the clinical setting.Disclosure of Interests:George E. Fragoulis: None declared, Gerasimos Evangelatos: None declared, Nikolaos Tentolouris: None declared, Kalliopi Fragkiadaki: None declared, Stylianos Panopoulos: None declared, George Konstantonis: None declared, Alexios Iliopoulos: None declared, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer
|
|
| 8. |
- Karpouzas, George Athanasios, et al.
(författare)
-
Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis
- 2024
-
Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 10:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA.Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease.Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk.Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.
|
|
| 9. |
- Roelsgaard, Ida K., et al.
(författare)
-
Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients
- 2020
-
Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:8, s. 1997-2004
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. Methods: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. Results: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. Conclusion: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.
|
|
| 10. |
|
|
