Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication ...of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.
Impact statement
Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.
To assess the risk of losing remission, low disease activity (LDA) or radiographic progression in the case of (1) discontinuing or (2) tapering doses of biological disease-modifying antirheumatic ...drugs (bDMARDs) compared with continuation of the initial treatment regimen in rheumatoid arthritis (RA) patients with remission or LDA.
A systematic literature analysis was carried out through May 2017 on the PubMed, Embase, Cochrane and international congress databases, selecting controlled trials comparing bDMARDs discontinuation/tapering versus continuation in RA patients with remission or LDA. The meta-analysis assessed the risk ratio (RR) and 95% CI of losing remission or LDA and the risk of radiographic progression after (1) discontinuing and (2) tapering doses of bDMARDs versus continuing the initial treatment.
The meta-analysis comparing bDMARDs discontinuation versus continuation performed on nine trials showed an increased risk of losing remission (RR (95% CI)=1.97(1.43 to 2.73), P<0.0001) or LDA (RR (95% CI)=2.24(1.52 to 3.30), P<0.0001) and an increased risk of radiographic progression (RR (95% CI)=1.09(1.02 to 1.17), P=0.01) in case of bDMARD discontinuation. The meta-analysis comparing bDMARDs tapering versus continuation performed on 11 trials showed an increased risk of losing remission (RR (95% CI)=1.23(1.06 to 1.42), P=0.006) but no increased risk of losing LDA (RR (95% CI)=1.02 (0.85 to 1.23), P=0.81) nor any increased risk of radiographic progression (RR (95% CI)=1.09(0.94 to 1.26), P=0.26) in case of bDMARD tapering.
Discontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission.
Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA ...prevalence is 133/100,000, while in the Italian population is 90-420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective.
The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study.
The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20.
Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionData concerning SARS-CoV-2 in patients affected by SLE are contradicting.The aim of this study was to investigate disease-related differences in COVID-19 prognosis of patients affected by ...rheumatic diseases before vaccination; we tested the hypothesis that patients with SLE may have a different outcome compared with those with rheumatoid arthritis (RA) or spondyloarthritis (SPA).MethodsWe analysed data from the national CONTROL-19 Database with a retrospective, observational design, including rheumatic patients affected by COVID-19. The principal outcome measure was hospitalisation with death or mechanical ventilation. Differences between SLE, RA and SPA were analysed by univariable and multivariable logistic regression models.ResultsWe included 103 patients with SLE (88.2% female, mean age 48.9 years, 50.4% active disease), 524 patients with RA (74.4% female, mean age 60.6 years, 59.7% active disease) and 486 patients with SPA (58.1% female, mean age 53.2 years, 58% active disease).Outcome prevalence was not different between patients with SLE and those with RA (SLE 24.5%, RA 25.6%), while patients with SPA showed a more favourable outcome compared with those with SLE (SPA 15.9%); data from the multivariable analysis confirmed this result.In SLE, age >65 years (OR 17.3, CI 5.51 to 63.16, p<0.001), hypertension (OR 6.2, CI 2.37 to 17.04, p<0.001) and prednisone (PDN) use (OR 3.8, CI 1.43 to 11.39, p=0.01) were associated with severe outcomes, whereas hydroxychloroquine use was found to be protective (OR 0.3, CI 0.14 to 0.91, p=0.03).ConclusionOur data suggest that patients with SLE and RA do not show a different COVID-19 outcome, while patients with SPA have a more favourable disease course compared with those with SLE. Risk of hospitalisation with ventilation or death was associated with age >65 years, hypertension and PDN use in patients with SLE.
Background:
Phenotypic features and outcome differences between sexes have been reported in psoriatic arthritis (PsA). However, little is known about sex differences in effectiveness of biologics in ...clinical practice.
Methods:
Post hoc
gender analysis of the CHRONOS, a multicenter, noninterventional, retroprospective Italian real-world study assessing 6-month and 1-year effectiveness of biologics for PsA.
Results:
Eligible patients were 399, 43.1% men. Sociodemographic characteristics, type of arthritis, baseline Disease Activity Score 28 joints (DAS28), and duration of biologic treatment were rather homogeneous. More men were overweight/obese and naive to biologics. The most frequently used biologics were TNF-inhibitors and secukinumab in both sexes. DAS28 responders were 72.7% (women) and 70.5% (men) at 6 months, and 68.0% in both sexes at 1 year. American College of Rheumatology (ACR) response showed a trend for men versus women to achieve more frequently ACR50 (32.6% vs. 26.5% at 6 months; 34.9% vs. 20.0% at 1 year) and ACR70 (22.3% vs. 12.4% at 6 months and 25.0% vs. 13.0% at 1 year). Global satisfaction with treatment at enrollment and after 6 months was slightly higher among men mean (standard deviation) Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) score: 68.6 (18.6) and 69.9 (18.2), respectively than women 65.3 (18.2), 66.2 (18.5).
Conclusions:
Overall response to biologics for PsA was rather favorable. With similar baseline disease severity, men appear to have a somewhat earlier and better response with higher treatment satisfaction.
Chronic pain in youth has an unsung etiology and limited treatment options. Affected adolescents show difficulties in different functioning domains, and their parents can develop associated distress, ...which negatively influences the adolescent’s capacity to adjust to pain. The aims of this study are the following: (1) to develop an internet-delivered (online) pain intervention (SMART4Pain) program for adolescents and their parents, and to test its feasibility and acceptability; (2) to evaluate, in adolescents, the impact of the face-to-face, randomized, two-armed (i.e., CBT or biofeedback), open-label pilot study, developed together with the online program. The overall program consisted of six sessions scheduled over six weeks. Twenty adolescents (N = 20) and their parents (N = 20) completed the entire program and are included in this study. The results showed that all interventions were feasible and acceptable, as well as potentially effective in improving quality of life. Only the group receiving the biofeedback intervention showed some improvements in psychological indicators of stress. In conclusion, more research is needed to better understand and develop new, multimodal rehabilitation programs in outpatient settings.
Objective:
To identify a spectrum of perspectives on functioning and health of patients with primary Sjögren's syndrome (pSS) from the five European countries in order to reveal commonalities and ...insights in their experiences.
Methods:
A multicenter focus group study on the patients with pSS about their perspectives of functioning and health was performed. Focus groups were chaired by trained moderators based on an interview guide, audiotaped, and transcribed. After conducting a meaning condensation analysis of each focus group, we subsequently combined the extracted concepts from each country and mapped them to the International Classification of Functioning, Disability and Health (ICF).
Results:
Fifty-one patients with pSS participated in 12 focus groups. We identified a total of 82 concepts meaningful to people with pSS. Of these, 55 (67%) were mentioned by the patients with pSS in at least four of five countries and 36 (44%) emerged in all the five countries. Most concepts were assigned to the ICF components
activities and participation
(
n
= 25, 30%), followed by 22 concepts (27%) that were considered to be
not definable
or
not covered
by the ICF; 15 concepts (18%) linked to
body structures and functions
. Participants reported several limitations in the daily life due to a mismatch between the capabilities of the person, the demands of the environment and the requirements of the activities.
Conclusion:
Concepts that emerged in all the five non-English speaking countries may be used to guide the development and adaption of the patient-reported outcome measures and to enhance the provision of treatment options based on the aspects meaningful to patients with pSS in clinical routine.
Abstract
Background
Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the ...present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice.
Methods
CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics.
Results
399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7–76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7–73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133).
Conclusions
The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.
BackgroundThere is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data ...from adults with RMDs or CYP without RMDs.ObjectivesTo describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA).MethodsWe described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry.ResultsA total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20–30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered.ConclusionsThis is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.
Ankylosing spondylitis (AS) is presented with axial and peripheral articular involvement. Uveitis is a severe and rather specific manifestation of AS. Biologics targeting tumor necrosis factor (TNF) ...α are effective on both articular and ocular manifestations of disease. The occurrence of uveitis in patients that never had eye involvement or the relapse of uveitis is described during anti-TNFα treatment. The frequency of these events is slightly higher during therapy with etanercept. The available TNFα blockers show different pharmacokinetics and pharmacodynamics yielding different biological effects. There is an ongoing debate whether uveitis during anti-TNFα has to be considered as paradoxical effect or an inadequate response to therapy. Here, we present a case report and review what the evidences for the two hypotheses are.
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