A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate ...immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet’s disease, gout, Sjögren’s syndrome, interstitial lung diseases, and Still’s disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems.
Abstract Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of the articular, gastrointestinal, ...neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach.
Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The ...anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients’ lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p<0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol’s fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient’s lipid profile in daily clinical practice.
The prevalence of sarcopenia in rheumatic diseases has been evaluated in single diseases using various diagnostic approaches, generating conflicting data on the pathogenetic mechanism(s). Herein, we ...evaluated both muscle mass index (MMI) and muscle strength to assess sarcopenia and presarcopenia in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Moreover, we evaluated the possible impact of disease/patient-related characteristics, therapeutic regimens, and nutritional aspects on sarcopenia. The present study included 168 patients of both genders, aged 40⁻75 years. All patients underwent a nutritional evaluation, physical activity level assessment, rheumatologic evaluation, and an MMI and muscle strength assessment. The prevalence of sarcopenia was about 20% in all the three rheumatologic diseases, whereas presarcopenia was significantly different in RA, PsA and AS (
= 0.006). At multivariate analysis, only age ≥60 years and the presence of a disability were associated with a significantly increased risk of sarcopenia (
= 0.006 and
= 0.01, respectively), while a higher C-reactive protein did not reach statistical significance. Sarcopenia is similar in RA, PsA and AS, whereas presarcopenia significantly differs in these three diseases. Disease activity/inflammation and nutritional aspects do not influence sarcopenia, while age ≥60 years and the presence of a disability significantly increase the risk of sarcopenia.
Abstract Objectives To assess the drug survival of golimumab, and predictors thereof, in patients affected with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA) in a ...prospective observational cohort. Methods This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2-years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analysed using Kaplan–Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. Results Of 416 patients starting golimumab, 171 biologic-naïve and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2-years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was gender female (HR 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR 4.19), and absence of extra-articular manifestations (HR 4.60). In PsA, duration of disease was negatively (HR 0.93), while golimumab monotherapy positively (HR 2.21) associated to drug interruption. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR 3.03). Conclusions This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.
In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis ...(axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy.
Objective
To assess circulating levels of derived reactive oxygen metabolites (ROMs) in patients with active rheumatoid arthritis (RA), before and during antitumour necrosis factor (TNF)-α therapy.
...Methods
Patients with active RA and failed previous treatment with disease-modifying antirheumatic drugs received subcutaneous anti-TNF-α for 52 weeks. Circulating hydrogen peroxide was quantified as a marker of oxidative stress at baseline and at 24 and 52 weeks.
Results
The study included 40 patients. Circulating dROM levels were significantly reduced compared with baseline after 24 and 52 weeks’ of anti-TNF-α treatment (33.2 ± 10.0 mgH2O2/dl, 29.5 ± 7.0 mgH2O2/dl and 29.3 ± 9.0 mgH2O2/dl, respectively). There was a significant direct correlation between disease activity score and ROM levels.
Conclusion
TNF-α inhibition can control disease activity and reduce circulating levels of reactive oxygen species in patients with RA.
Abstract Objectives The aim of this study was to assess whether body mass index (BMI) affects clinical outcomes in rheumatoid arthritis (RA) patients starting a second line biological drug after ...failure of a first TNF-α blocker. Methods From a longitudinal cohort, we analyzed 292 RA patients (66 obese, 109 overweight, and 117 normal-weight) treated with a first ever anti-TNF-α drug. Patients discontinuing the therapy were followed-up if began a second biological drug. Drug survival, by Kaplan-Meier life analysis, and 12 months disease remission based on the 28-joint Disease Activity Score (DAS28) were assessed for either course of biologics. The baseline predictors of clinical outcomes were assessed by Cox regression analysis. Results Survival of the first anti-TNF-α drug was lower in obese (39.4%) than in normal-weight (49.1%) patients, but the difference was not statistically significant. Obese patients had the highest hazard to discontinue the first anti-TNF-α drug (HR 1.64, 1.02–2.62 95% IC, P = 0.04), and the lowest percentage of DAS28-based disease remission at 12 months ( P = 0.04). In 97 (37 normal-weight, 36 overweight, 24 obese) patients who started a second non-anti-TNF-α biological drug, persistence on therapy was significantly lower in obese (43.5%) than in normal-weight (80%, P = 0.04) group, and again obesity significantly predicted drug discontinuation (HR 2.9, 1.08–8.45 95% IC, P = 0.04). Significantly, less obese patients attained a disease remission (12%, P = 0.004) at 12 months. Conclusion Our study provides evidence that obese RA patients poorly respond to second line non-anti-TNF-α drugs after failure of a first TNF-α inhibitor.
Temporomandibular disorders (TMD) represent a heterogeneous group of inflammatory or degenerative diseases of the stomatognatic system, with algic and/or dysfunctional clinical features involving ...temporomandibular joint (TMJ) and related masticatory muscles. Rheumatoid Arthritis (RA) is an autoimmune polyarthritis characterized by the chronic inflammation of synovial joints and oral implications such as hyposalivation, difficulty in swallowing and phoning, feeling of burning mouth, increased thirst, loss of taste or unpleasant taste and smell, dental sensitivity. The aim of this observational study was to investigate the prevalence of TMD symptoms and signs as well as oral implications in patients with Early Rheumatoid Arthritis (ERA), that is a RA diagnosed within 12 months, compared with a control group.
: The study group included 52 ERA patients (11 men, 41 women) diagnosed according to the 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis. A randomly selected group of 52 patients not affected by this disease, matched by sex and age, served as the control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) by means of a questionnaire and through clinical examination.
Regarding the oral kinematics, the left lateral excursion of the mandible was restricted in statistically significant way in ERA patients (
=0.017). The endfeel values were significantly increased in ERA group (
=0.0017), thus showing the presence of a higher muscle contracture. On the other side, the study group complained less frequently (67.3%) of TDM symptoms (muscle pain on chewing, pain in the neck and shoulders muscles, difficulty in mouth opening, arthralgia of TMJ, tinnitus) than controls (90.4%) (χ
= 8.301
=0.0039). The presence of TMJ noises was significantly lower in the study group (χ
= 3.869
=0.0049), as well as presence of opening derangement (χ
= 14.014
=0.0002). The salivary flow was significantly decreased in the study group respect to the control one (
<0.0001).
The data collected show a weak TMJ kinematic impairment, a paucisymptomatic muscle contracture (positive endfeel) and a remarkable reduction of salivary flow in ERA patients. Myofacial pain (MP) evoked by palpation was more frequent and severe in the control group than in the study one, this result being highly significant.
PDF
