An accurate prediction of cardiovascular (CV) risk in patients with Axial Spondyloarthritis (axSpA) is a strong unmet need, as CV risk algorithms poorly perform in these subjects. The aim of this ...study was to establish whether the persistence of high C-reactive protein (CRP) and high disease activity may be considered predictive factors of CVD in axSpA. 295 patients without personal history of CVD, were consecutively enrolled in this study. To evaluate the relationship between CV events occurrence (fatal and non-fatal) and the persistence of increased CRP levels, ASDAS (Ankylosing Spondylitis Disease Activity Score) > 2.1, and BASDAI (Bath Ankylosing Spondylitis Disease Activity) > 4 during the follow-up, univariable and multivariable Cox Proportional Hazard Models have been performed. During follow-up (we analyzed 10-years retrospective data), 23 patients had a CV event. Multivariable Cox Proportional Hazard Models showed a strong association between CV event and the persistency of increased CRP levels (namely, percentage of visits in which CRP levels were increased) (HR = 1.03; 95%CI 1.015-1.045; p < 0.001), of ASDAS > 2.1 (HR = 1.014, 95%CI 1.000-1.028, p = 0.047), and of BASDAI > 4 (HR 1.019, 95%CI 1.006-1.033, p = 0.006) during follow-up, after adjustment for age, sex, and diabetes. This study suggests that persistence of increased CRP levels and high disease activity may be considered biomarkers to identify those axSpA patients at higher risk of CVD. Innovative axSpA-specific CV risk score, including these variables, have to be developed.
Macrophage activation syndrome (MAS) is a severe, hyperinflammatory life-threatening syndrome, generally complicating different rheumatic diseases. Despite the severity of the disease, little is ...known about the pathogenic mechanisms and, thus, possible targeted therapies in the management of these patients. Areas covered: In this review, we aimed to update the current pathogenic knowledge of MAS, during rheumatic diseases, focusing mainly on immunologic abnormalities and on new possible therapeutic strategies. Expert commentary: The difficult pathogenic scenario of MAS, in which genetic defects, predisposing diseases, and triggers are mixed together with the high mortality rate, make it difficult to manage these patients. Although most efforts have been focused on investigating the disease in children, in recent years, several studies are trying to elucidate the possible pathogenic mechanism in adult MAS patients. In this context, genetic and immunological studies might lead to advances in the knowledge of pathogenic mechanisms and possible new therapeutic targets. In the future, the results of ongoing clinical trials are awaited in order to improve the management and, thus, the survival of these patients.
The clinical diagnosis of rheumatoid arthritis is supported by imaging findings. MR imaging, in particular, can allow an early diagnosis to determine a target therapy that can stop or at least slow ...the disease progression.
The aim of this observational study was to assess safety and efficacy of certolizumab pegol (CZP) in a real-life cohort of patients affected by psoriasis (PsO) and psoriatic arthritis (PsA), who had ...an inadequate response to previous systemic immunosuppressive treatments, with a follow-up of 24 weeks.
Twelve patients with PsO and PsA, referring to our Dermatology/Rheumatology combined outpatient clinic, were enrolled. Primary endpoints were safety and efficacy of CZP, defined as statistically significant improvement of DAPSA, clinical DAPSA and PASI. Secondary endpoints validated clinical and laboratory measures and patient-reported outcomes.
CZP injections were well-tolerated. We observed a rapid and significant improvement in all primary endpoints, in the 24-week treatment period of the study. We described positive effects of CZP in several domains, including joint and skin involvement, pain, patient and physician global assessment, physical function, and health-related quality of life. CZP was effective and safe in patients who were either naïve or previously unresponsive to other anti-TNFα. No difference was found in terms of efficacy and safety between patients treated with CZP monotherapy and patients in combination therapy with methotrexate.
CZP was safe and effective in a real-life cohort of patients affected by PsO and PsA, who have had an inadequate response to previous systemic treatments.
The principle of ketogenic diet (KD) is restriction of carbohydrates to a maximum of 5-10% of the total daily caloric intake, aiming at shifting body metabolism toward ketone bodies. Different ...studies suggested promising results of KD to help patients to lose weight, to reduce insulin requirements in diabetes, to supplement cancer protocols, to treat neurological conditions and to optimize control of metabolic and cardiovascular diseases. However, literature about the anti-inflammatory properties of KD in rheumatic diseases is still limited. The beneficial effects of weight loss in patients with inflammatory arthritis can be explained by biomechanical and biochemical factors. Obesity is associated with macrophage activation and production of pro-inflammatory cytokines including TNF-α, IL-1b, and IL-6. The clinical effect of KD may be primarily attributed to improvement of insulin sensitivity. Insulin resistance is associated with an increase of TNF-α, IL-1α, IL-1β, IL-6, and leptin. Moreover, reduction of body's adipose tissue and weight loss account for part of the anti-inflammatory effects and for the impact of KD on cardiovascular health. In rheumatoid arthritis, fasting was shown to be effective in reducing disease symptoms, possibly through the production of β-hydroxybutyrate (BHB), the main ketone body. BHB may exert inhibitory effects also on IL-17 and intermittent fasting improved the clinical manifestations of psoriatic arthritis. In ankylosing spondylitis, current literature doesn't allow to draw conclusion about the effects of KD. Future prospective studies will be needed to elucidate the potential beneficial effects of KD on specific domains and clinical outcomes in patients with inflammatory arthritis.
Anakinra (ANA) is an effective treatment choice in patients with adult onset Still's disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the ...decision to discontinue treatment after long-term clinical remission.
Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission.
AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (
), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed.
One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank
= 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank
= 0.45); (iii) systemic and chronic articular types of AOSD (log-rank
= 0.67). No variables collected at
could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (
= 0.01, OR = 1.194, C.I. 1.043-1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (
= 0.03, OR = 0.224, C.I. 0.058-0.863).
Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.
Introduction
Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in ...patients with PsA in a “real-life” multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up.
Methods
Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR.
Results
A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (
β
− 15.47,
p
= 0.001, 95% CI − 23.15 to − 9.79) with 39.6% of patients achieving a DAPSA ≤ 14.
At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs.
Conclusion
The “real-life” 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.
COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of ...pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization.
This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays.
In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048).
treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1β from M2 macrophages was observed when compared to controls (p<0.05).
PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1β production.
Although in the past, prevention of the joint destruction and disability was strongly emphasised in Rheumatoid Arthritis (RA), at present, a growing body of evidence is focused at identifying the ...best management of associated comorbidities, such as Type 2 Diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients.
We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process.
After literature search, the available evidence has been selected and commented in the text.
During RA, it is well known that different inflammatory cytokines, such as interleukin-1β (IL-1β), are pivotal pathogenic mediators and their role has been largely confirmed in clinical settings. Similarly, it has been shown that the excess of nutrients, secondary to over-nutrition, may activate the immune system, leading to an increased production of inflammatory cytokines, including IL-1β, suggesting new possible therapeutic targets.
Although further studies are needed to fully investigate the pathogenic interplay between inflammation and metabolic disorders, IL-1β has been implicated in both RA and T2D pathogenic mechanisms. Intriguingly, the potential role of anti-IL-1 drugs has been proposed in RA patients affected by T2D.
During rheumatoid arthritis (RA), the pathogenic role of resident cells within the synovial membrane is suggested, especially for a population frequently referred to as fibroblast-like synoviocytes ...(FLSs). In this study, we assess the markers of myofibroblast differentiation of RA-FLSs by ex vivo observations and in vitro evaluations following the stimulation with both TGF-β and IL-6. Furthermore, we investigated the possible inhibiting role of tofacitinib, a JAK inhibitor, in this context. Myofibroblast differentiation markers were evaluated on RA synovial tissues by immune-fluorescence or immune-histochemistry. RA-FLSs, stimulated with transforming growth factor (TGF-β) and interleukin-6 (IL-6) with/without tofacitinib, were assessed for myofibroblast differentiation markers expression by qRT-PCR and Western blot. The same markers were evaluated following JAK-1 silencing by siRNA assay. The presence of myofibroblast differentiation markers in RA synovial tissue was significantly higher than healthy controls. Ex vivo, α-SMA was increased, whereas E-Cadherin decreased. In vitro, TGF-β and IL-6 stimulation of RA-FLSs promoted a significant increased mRNA expression of collagen I and α-SMA, whereas E-Cadherin mRNA expression was decreased. In the same conditions, the stimulation with tofacitinib significantly reduced the mRNA expression of collagen I and α-SMA, even if the Western blot did not confirm this finding. JAK-1 gene silencing did not fully prevent the effects of stimulation with TGF-β and IL-6 on these features. TGF-β and IL-6 stimulation may play a role in mediating myofibroblast differentiation from RA-FLSs, promoting collagen I and α-SMA while decreasing E-Cadherin. Following the same stimulation, tofacitinib reduced the increases of both collagen I and α-SMA on RA-FLSs, although further studies are needed to fully evaluate this issue and confirm our results.
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