1,721,342 research outputs found
Therapeutic peptides for the treatment of systemic lupus erythematosus: a place in therapy
No full textIntroduction Studiesin vitroandin vivohave identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly based on the induction of immune tolerance. Three therapeutic peptides have entered clinical development, but they have yielded disappointing results. However, some subsets of patients, such as those with the positivity of anti-dsDNA antibodies, appear more likely to respond to these medications. Areas covered This review evaluates the potential use of therapeutic peptides for SLE and gives an opinion on how they may offer advantages for SLE treatment. Expert opinion Given their acceptable safety profile, therapeutic peptides could be added to agents traditionally used to treat SLE and this may offer a synergistic and drug-sparing effect, especially in selected patient populations. Moreover, they could temporarily be utilized to manage SLE flares, or be administered as a vaccine in subjects at risk. Efforts to ameliorate bioavailability, increase the half-life and prevent immunogenicity are ongoing. The formulation of hybrid compounds, like peptibodies or peptidomimetic small molecules, is expected to yield renewed treatments with a better pharmacologic profile and increased efficacy
Anti-IL-17 Agents in the Treatment of Axial Spondyloarthritis
Full text link: Axial spondyloarthritis (axSpA) describes a group of chronic inflammatory rheumatic diseases primarily involving the axial skeleton. IL-17 is involved in the pathogenesis of numerous inflammatory diseases, including inflammatory arthritis. Until a few years ago, the only biological agents licensed for the treatment of axSpA and nr-axSpA were TNF inhibitors. However, as some patients did not respond to TNF inhibition or experienced secondary failure, the introduction of the first two IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) has extended the treatment options, and there are now three others (bimekizumab, brodalumab and netakimab) in various stages of clinical development. The last ten years have seen the development of a number of therapeutic recommendations that aimed at improving the management of axSpA patients. The aim of this narrative review of the published literature concerning the role of IL-17 in the pathogenesis of SpA, and the role of IL-17 inhibitors in the treatment of axSpA, is to provide a comprehensive picture of the clinical efficacy and safety of the drugs themselves, and the treatment strategies recommended in the international guidelines
Cardiovascular Involvement in Sjögren’s Syndrome
No full textSjögren Syndrome (SS) seems to be associated with a greater “overall risk” of cardiovascular (CV) and cerebrovascular events. Although not conventionally considered a feature of the disease, CV events represent a major burden in SS patients. CV risk is the consequence of a complex combination of multiple factors, including traditional risk factors and disease-related mechanisms. A complex relationships between disease-related features, endothelial dysfunction and traditional risk factor has been suggested. Several drugs are available for treating the systemic manifestations of SS, however they have shown positive effects on different outcomes of the disease, but until today the data on the role of these drugs on CV events are scarse. Given these data, the aim of this review was to evaluate the risk of CV risk in primary SS and the effect of the drugs on this manifestation
Potential Role of Anti-interleukin (IL)-6 Drugs in the Treatment of COVID-19: Rationale, Clinical Evidence and Risks
Full text linkThe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. This public health emergency has triggered a race to find medications to improve the prognosis of this disease. There is currently great interest in drug repositioning to manage SARS-CoV-2 infection, that is, the evaluation of the potential benefits of a drug that has already been proven safe and effective in humans for other approved indications. As interleukin-6 (IL-6) acts as a key driver of the inflammation associated with coronavirus disease 2019 (COVID-19), IL-6 and IL-6 receptor (IL-6R) inhibition appear to be promising targets for the treatment of COVID-19 patients. It is important to critically analyze the available evidence concerning the use of the available anti-IL-6 (siltuximab) and anti-IL-6R (tocilizumab and sarilumab) agents in COVID-19 patients, in terms of both benefit and risk. In this review, the pathogenesis of the cytokine storm induced by COVID-19, the role of IL-6 in this cytokine storm, the rationale for the use of anti-IL-6 agents, and key information on potential benefits and safety monitoring of these biologicals in COVID-19 patients is discussed
Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis
No full textIntroduction: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA.
Areas covered: In this review, we provide an overview of possible mechanisms underlying pain in IA and its assessment, as well as the effects of bDMARDs and JAKi on pain management.
Expert opinion: The overall data showed a good effect of bDMARDs and JAKi on pain, more pronounced for JAKi. However, it is challenging to distinguish the effect on the different types of pain (nociceptive, neuropathic, and nociplastic)
Pain in systemic connective tissue diseases
Full text linkPain is frequent in patients with connective tissue diseases
(CTDs), particularly those affected by systemic sclerosis (SSc) and
systemic lupus erythematosus (SLE) in which it is virtually
ubiquitous and can have different causes. The SLE classi
fi
cation
criteria include pain associated with musculoskeletal involve-
ment, which are frequently the initial symptom of SLE and can
include arthralgia, arthritis and/or myalgia. Chronic widespread
pain, the cornerstone of
fi
bromyalgia (FM), is also frequently
associated with CTDs.
Chronic pain has a considerable impact on mental health, and the
professional and family lives of patients. It can be due to many
disorders, but there are few reports concerning its prevalence
during the course of other diseases.
It is essential to identify the origin of pain in CTDs in order to avoid
dangerous over-treatment in patients with co-existing widespread
pain. Effective pain management is a primary goal of patient
care, although it has not been investigated in detail in patients
with SSc
Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications
No full textFibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups
C-reactive protein level association with future cardiovascular events assessed by different risk scores among rheumatoid arthritis patients
No full textC-reactive protein level association with future cardiovascular events assessed by different risk scores among rheumatoid arthritis patients
Rheumatoid Arthritis disease activity assessment in routine care: performance of the most widely used composite disease activity indices and patient-reported outcome measures
No full textBackground and aim: To evaluate the convergent and discriminative validity of many continuous composite disease activity indices and patient-reported outcome measures (PROMs) in rheumatoid arthritis (RA).
Methods: In consecutive RA patients in moderate or high disease activity, according to the Simplified Disease Activity Index (SDAI) definition, were computed four additional composite disease activity indices, the 28-joint Disease Activity Score - erythrocyte sedimentation rate (DAS28-ESR), the Clinical Disease Activity Index (CDAI), the Chronic Arthritis Systemic Index (CASI), and the Mean Overall Index for RA (MOI-RA), and five PROMs, the Patients' Activity Scale (PAS), the Rheumatoid Arthritis Impact of Disease (RAID), the 5-item RA Disease Activity Index (RADAI-5), the Routine Assessment of Patient Index Data (RAPID3), and the Clinical Arthritis Activity (PRO-CLARA). Spearman's rho correlation coefficients were determined to assess their convergent validity, and discriminative performance was calculated by the area under the receiver-operating curve (AUC-ROC). The patients' opinion of their symptomatic status (PASS) was used as the external criterion.
Results: 246 RA patients with moderate (29.3%) or high disease activity (70.7%) have been assessed. The indices all showed a significant correlation (p <0.0001 for all). Among the composite disease activity indices, the CDAI was the one that showed the best discriminating ability compared to the PASS (AUC = 0.962), while among the PROMs the RAID was the most performing (AUC = 0.879).
Conclusions: CDAI as composite index of disease activity, and RAID as PROM, are the two instruments with the best performances in relation to PASS. The use of validated disease activity measures can help in clinical practice to adopt treat-to-target strategies in RA patients
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