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Psoriatic arthritis (PsA) is a chronic multi-faceted immune-mediated systemic disorder, characterized by articular, cutaneous, enthesis, nail and spine involvement. Articular ...manifestations of PsA are particularly common and highly disabling for patients, while the heterogeneous clinical subsets of the disease are challenging for clinicians. In recent years, research has made many advances in understanding the pathogenesis of the disease from genetic, epigenetic and molecular points of view. New drugs are now available for the treatment of this condition, and, in particular, TNF-alfa inhibitors, historically the first biologicals approved in PsA, are now juxtaposed by new biological disease modifying anti-rheumatic drugs (bDMARDs) with different modes of action. Targeting IL-12/IL-23 p40 common subunit with ustekinumab, IL-17A with secukinumab and ixekizumab, T cells co-stimulation with abatacept, is now possible, safe and effective. Moreover, targeted synthetic molecules with oral administration are available, with the possibility to interfere with phosphodiesterase-4 and JAK/STAT pathways. Indeed, new drugs are under development, with the possibility to target selectively IL-17 receptor, IL-23, and other key molecular targets in the pathogenesis of this condition. In this narrative review, we provide an up-to-date overview of the current application of biological and targeted synthetic DMARDs in the field of PsA, with particular regard to the clinical significance of this possibility to target a higher number of distinct immune-pathways.
•Infliximab can delay bone healing.•TNF-α is a important key to bone healing.•Less bone deposition is related to TNF blockade.•Infliximab can reduce the expression of bone metabolism markers.
TNF-α, ...which acts directly on osteoclastogenesis, may modify bone turnover. Thus, the objective of this study was to evaluate the influence of infliximab on extraction socket healing.
Eighty-four Wistar rats were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1 ml / kg) and submitted to lower first molar extraction protocol. The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The jaws were subjected to radiographic, histomorphometric, histochemical (picrosirius red) and immunohistochemical (TNF-α, RANKL and OPG) analysis.
No differences were observed between the groups in surgical difficulty parameters: mass of teeth, number of root fractures and surgical time. Lower area filling with bone as well as increased amounts of remaining cicatricial tissue were observed in the infliximab group at 14 days (p < 0.001). Lower scores for polymorphonuclear neutrophils were seen at 3 (p < 0.01) and 7 days (p < 0.001), lower mononuclear counts at 7 days (p < 0.01) and lower osteoclast counts at 7 and 14 days (p < 0.01 and p < 0.001, respectively). Additionally, reduced TNF-α, RANKL and OPG immunoreactivity were observed, especially at 7 days (p < 0.05).
TNF-α inhibitor may alter the bone repair capacity after tooth extraction, especially in the initial repair periods, by lower expression of TNF α, RANKL and OPG. Thus, additional caution may be needed in patients who use this class of medication after dental extraction.
Preeclampsia is a serious medical condition that significantly affects expectant mothers. Growing research showed an inconsistent association between TNF-alfa rs1800629 polymorphism and preeclampsia. ...The current meta-analysis was aimed at examining the potential impact of rs1800629 variant on preeclampsia.
The Cochrane Library, Google Scholar, PubMed, EMBASE, Web of Science, and other databases were searched extensively to locate and select articles up to October 30, 2023. The PRISMA 2020 recommendations were followed to perform this study. Data analysis was done by using Comprehensive Meta analysis (v 3).
We have included 32 articles containing 35 studies with 3,883 patients and 5,821 controls for qualitative and quantitative data analysis. We found a strong relationship between rs1800629 variant with the increased preeclampsia risk in co-dominant model 1 (OR = 1.33, p = 0.019), co-dominant model 2 (OR = 1.43, p = 0.014), dominant model (OR = 1.25, p = 0.044), over-dominant model (OR = 1.31, p = 0.021), and allelic model (OR = 1.24, p = 0.018). This study also revealed a significantly higher risk among the Asian population in the dominant (OR = 2.31, p = 0.036) and allelic model (OR = 2.02, p = 0.028). For the Caucasian population, an increased association between the rs1800629 variant and preeclampsia risk was reported in co-dominant model 1 (OR = 1.37, p = 0.011), co-dominant model 2 (OR = 1.77, p = 0.007), dominant model (OR = 1.32, p = 0.030), recessive (OR = 1.50, p = 0.047), over-dominant (OR = 1.34, p = 0.009), and allelic model (OR = 1.32, p = 0.004). Though our study showed the protective link of the TNF-alfa polymorphism to the preeclampsia risk among the Black population, no significant outcomes were observed in any genetic models (p > 0.05).
Overall, the present meta-analysis explored a consistent linkage of the TNF-alfa rs1800629 variant to the preeclampsia risk in different ethnic groups. Additional research is required to confirm the precise relationship between the rs1800629 variant and preeclampsia risk.
Neurosarcoidosis is a rare and serious condition. Rapid diagnosis and treatment are crucial to prevent morbidity and mortality. When neurological symptoms are not present at the time of diagnosis, ...CNS involvement can be undetected. We present a case of neurosarcoidosis complicating Löfgren's syndrome and discus the challenges in diagnostics and treatment, that can be encountered.
Abstract
Objectives
The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no ...clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors.
Methods
A prospective study for up to 6 months following transition was conducted. Outcome measures of interest include clinical characteristics at time of transition and disease activity scores (Disease Activity Score-28 DAS28 for RA, Bath Ankylosing Spondylitis Disease Activity Index BASDAI for axSpA) over time and safety.
Results
One-hundred and eleven subjects (out of the 557 in total enrolled in the study) were derived from 8 Italian sites, including 79 with RA and 32 with axSpA. In both cohorts, the efficacy was maintained at 3 months and 6 months from the transition to the biosimilar with no significant change in mean DAS28 and BASDAI scores: at the end of the 6 months of observation the mean DAS28 and BASDAI was similar to baseline (confidence interval CI −0.22, 0.22), while the mean variation of the BASDAI was −0.14. Of note, 100.0% (95% CI 89.1, 100.0) in the axSpA and 90.8% (95% CI 81.5, 95.5) in the RA cohort of patients continued to receive SB4 at month 6 (binary variable with 95% Clopper-Pearson CI).
Conclusions
Italian patients with stable RA or axSpA who transitioned from originator Etanercept to SB4 maintained clinical response at 6 months post-transition. Both the cohorts are representative of typical patients with long-standing established diagnoses. Most of the patients transitioned to the same dose regimen of biosimilar as that received for the originator, and the regimen remained unchanged at 6 months, supporting the effectiveness of the transition.
Behçet disease is a rare vasculitis that affects vessels of different body parts, causing different kinds of manifestations. We report a case of a 47 years old woman who had a tumor necrosis factor ...alfa blocker prescription due to a Behçet's disease relapse. The patient then developed a cerebral and pulmonary tuberculous miliary due to immunodeficiency. The aim of this work is to show that tuberculosis infection is a common complication of the administration of tumor necrosis factor alfa blocker, and the importance to perform a tuberculosis screening before starting the treatment.
Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated ...with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation. The latter might be considered as one of the factors damaging neuronal cells. Several cell types trigger and sustain such neuroinflammation. In this study, we traced different markers of immune system activation on both cellular (immune cell phenotypes) and mediatory levels (production of cytokines) alongside adverse hematology and biochemistry screening in a group of autistic children. In addition, we analyzed the main metabolic pathways potentially involved in ASD development: energy (citric acid cycle components), porphyrin, and neurotransmitter metabolism. Several ASD etiological factors, like heavy metal intoxication, and risk factors-genetic polymorphisms of the relevant neurotransmitters and vitamin D receptors-were also analyzed. Finally, broad linear regression analysis allowed us to elucidate the possible scenario that led to the development of chronic inflammation in ASD patients. Obtained data showed elevated levels of urinary cis-aconitate, isocitrate, alfa-ketoglutarate, and HMG. There were no changes in levels of metabolites of monoamine neurotransmitters, however, the liver-specific tryptophan kinurenine pathway metabolites showed increased levels of quinolinate (QUIN) and picolinate, whereas the level of kynurenate remained unchanged. Abovementioned data demonstrate the infringement in energy metabolism. We found elevated levels of lead in red blood cells, as well as altered porphyrin metabolism, which support the etiological role of heavy metal intoxication in ASD. Lead intoxication, the effect of which is intensified by a mutation of the VDR-Taq and MAO-A, leads to quinolinic acid increase, resulting in energy metabolism depletion and mitochondrial dysfunction. Moreover, our data backing the CD4+CD3+ T-cell dependence of mitochondrial dysfunction development in ASD patients reported in our previous study leads us to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients.
The level of competition achieved following biosimilars market availability varies by country, care setting and molecule. Hence, biosimilars contribution to attaining price reductions and extended ...access to treatments can also vary.
The aim of this study is to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors and competing molecules in Southern European markets (2011-2020), and to evaluate the benefits of the competition generated by the availability of biosimilars.
This study is based on a literature review examining market characteristics for TNF-alfa inhibitors and competing immunomodulator molecules, and on the quantitative analysis of market data for these molecules in Italy, Portugal and Spain.
Following biosimilars availability in Italian, Portuguese and Spanish markets, there has been an expansion in the overall access to TNF-alfa inhibitor pharmaceuticals. Further, savings have been generated within the TNF-alfa inhibitors class even after the increased use of these molecules. However, the potential of infliximab, etanercept and adalimumab biosimilars to generate price competition outside of their own drug class appeared limited in the studied markets. Considering this limitation and that shifts towards on-patent and higher-cost therapies have occurred after TNF-alfa inhibitor biosimilars availability, the importance of investing in biosimilars development for still on-patent immunology biologics is emphasized.
This study highlights the need for policies that do not only seek higher utilization of biosimilars, but that also support a sustainable market for these products. This is expected to foster the future development of biosimilar medicines.
Abstract Objectives To describe the response to IL-6 blockade tocilizumab (TCZ) in three patients affected by highly refractory neuro-Behçet disease (NBD). Methods Three patients who had failed ...synthetic immunosuppressants and TNF-α antagonists combined with glucocorticoids received TCZ after obtaining their informed consent. Two patients underwent TCZ infusions at 8 mg/kg every 4 weeks for a mean period of 24 months, while in one patient, the frequency of TCZ infusions was increased to every other week after 21 months due to a disease flare. Concomitant therapy with synthetic agents and low-to-medium dose glucocorticoids was continued. Clinical and imaging findings were assessed before and after the onset of TCZ therapy. Results In all our patients, a very short time lag between the onset of treatment with TCZ and the clinical response was observed. A partial response occurred in two patients and a nearly complete response in one. Some loss of efficacy occurred after 18 months in one patient, but there was again a significant improvement when the interval between the infusions was shortened. TCZ was overall well tolerated and no serious adverse events occurred. In two patients, the prednisone dose could successfully be tapered to about 20 mg/day, while in another patient glucocorticoids could safely be withdrawn. Brain MRI remained virtually unchanged in all patients. Conclusions Although TCZ has not yet been included among the medications recommended for the treatment of NBD, our data suggest that it may be considered for patients with refractory NBD.
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