Search Results (64)

Background: The management of rheumatoid arthritis (RA) has advanced significantly with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). Despite these therapeutic strides, RA prognosis remains profoundly affected by comorbid conditions, particularly cardiovascular and metabolic complications, which increase both morbidity and mortality. The role of bDMARDs in modulating comorbidities remains underexplored, with limited evidence on their effects across various non-RA conditions, such as respiratory, diabetic, and hematologic disorders. This systematic review aimed to evaluate the impact of bDMARDs on the progression and outcomes of comorbidities in RA patients, providing insights to guide personalized treatment approaches. Methods: This systematic review was registered in PROSPERO (CRD42022345903) and followed the PRISMA guidelines. Original research articles from PubMed and Scopus, published up to 18 July 2024, were included. Studies assessing the impact of bDMARDs on comorbidities in RA patients met the eligibility criteria. Results: A total of thirteen studies met the inclusion criteria. They were published from inception until July 2024. The studied comorbidities included pulmonary conditions (asthma, chronic obstructive pulmonary disease, and interstitial lung disease) (n = 2); diabetes (n = 3); anemia (n = 3); and malignancies (n = 3). The bDMARDs studied were tumor necrosis factor inhibitors (TNFis) (n = 9); Rituximab (n = 5); Tocilizumab (n = 5); Abatacept (n = 5); and Anakinra (n = 2). The most reported effects of bDMARDs on comorbidities were the following: (i) an exacerbation of pulmonary comorbidities for Abatacept and TNFis; (ii) patients switched to or initiated on Abatacept as their first targeted disease-modifying antirheumatic drug (tDMARD) showed directionally lower rates and costs of T2DM-related complications compared with patients switching to or initiating other tDMARDs; (iii) there was no difference between Abatacept and TNFis or Rituximab/Tocilizumab regarding diabetes treatment switching or intensification; (iv) Anakinra significantly reduced the HbA1c%; (v) decreased serum hepcidin levels and improvement in anemia were observed in patients treated with TNFis or Tocilizumab; and (vi) no decrease in overall survival time or the significant incident malignancy rate was noted in RA patients. Conclusions: Overall, bDMARDs appear safe for use in RA patients with comorbidities and may even provide specific benefits for conditions such as anemia and diabetes. These findings suggest that clinicians could consider tailoring biologic therapy based on each patient’s comorbidity profile, potentially enhancing both RA management and comorbidity outcomes. For instance, selecting biologics such as Anakinra or Tocilizumab might be advantageous for RA patients with concurrent diabetes or anemia, given their observed metabolic and hematologic benefits. This personalized approach could improve the quality of life and reduce healthcare costs by addressing RA and associated comorbidities more effectively. Full article

Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (≥18 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease. Full article

Background: Juvenile scleroderma (JS) comprises a group of rare chronic autoimmune and fibrosing disorders in children, primarily presenting as juvenile localized scleroderma (jLS) or juvenile systemic sclerosis (jSS). While jLS predominantly affects the skin and subcutaneous tissues, jSS may involve multiple internal organs and is associated with increased morbidity and mortality. Due to the scarcity of pediatric-specific clinical trials, the current treatment strategies are largely empirical and often adapted from adult protocols. Objective: This narrative review aims to provide a comprehensive update on emerging systemic therapies for juvenile scleroderma, focusing on biologics, small molecule inhibitors, and advanced cellular interventions, to support the development of more personalized and effective pediatric treatment approaches. Methods: A literature search was conducted through PubMed and a manual bibliographic review, covering publications from 2001 to 2024. Only English-language studies involving pediatric populations were included, comprising randomized controlled trials, reviews, and case reports. Additional searches were performed for drugs that are specifically used in juvenile scleroderma. Results: Biologic agents such as tocilizumab, rituximab, and abatacept, along with small molecules including Janus kinase (JAK) inhibitors and imatinib, have demonstrated potential in managing refractory cases by reducing skin fibrosis and pulmonary involvement. Novel approaches—such as pamrevlumab, nintedanib, and chimeric antigen receptor (CAR-T) cell therapy—target fibrotic and autoimmune pathways but remain investigational in children. Autologous stem cell transplantation (ASCT) has also been explored in severe, treatment-resistant cases, although data are extremely limited. The overall evidence base is constrained by small sample sizes, a lack of controlled pediatric trials, and reliance on adult extrapolation. Conclusions: While innovative systemic therapies show promise for juvenile scleroderma, their widespread clinical application remains limited by insufficient pediatric-specific evidence. Large, multicenter, long-term trials are urgently needed to establish safety, efficacy, and optimal treatment algorithms that are tailored to the pediatric population. Full article

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) significantly affects disease prognosis and patient survival. The impact of conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic DMARDs (b/tsDMARDs) on RA-ILD prognoses remains unclear. This study aimed to investigate the effects of csDMARDs and b/tsDMARDs on RA-ILD progression and prognosis based on pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and symptom changes. Methods: This multicenter, retrospective, observational study included patients with RA-ILD at 13 referral hospitals in South Korea. The participants were categorized into csDMARD-only and b/tsDMARD-exposed groups. RA-ILD prognosis was assessed over a 24-month follow-up period using serial PFTs (the forced vital capacity [FVC] and diffusing capacity of the lungs for carbon monoxide [DLCO]), HRCT findings, and clinical symptom changes. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare disease progression risk while adjusting for baseline lung function, RA disease activity, and glucocorticoid use. Results: Among 127 eligible patients, 22 (17.3%) were exposed to b/tsDMARDs, predominantly abatacept and tocilizumab. During a mean follow-up of 2.8 years, 65 (51.2%) patients experienced RA-ILD progression. A higher baseline Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR) (adjusted hazard ratio [aHR]: 1.344, 95% confidence interval [CI]: 1.136–1.590, p = 0.001) and initially prescribed prednisone dose (aHR: 1.078, 95% CI: 1.011–1.151, p = 0.023) were significant prognostic factors for ILD progression. No statistically significant difference in progression risk was observed between the csDMARD-only and b/tsDMARD-exposed groups (aHR: 0.937, p = 0.851). Conclusions: The RA-ILD prognosis was more strongly influenced by disease activity, rather than the type of DMARD used. These findings emphasize the importance of maintaining low RA disease activity to improve RA-ILD prognosis. Full article

Background/Objectives: Arthritis encompasses a range of joint-related conditions, including osteoarthritis and rheumatoid arthritis, along with inflammatory diseases such as gout and lupus. This research study explores the underlying causes, challenges, and treatment options for arthritis, aiming to enhance the effectiveness of therapies. Methods: This research study evaluated current treatment strategies and examined the effectiveness of selected biological disease-modifying antirheumatic drugs (bDMARDs), i.e., abatacept, golimumab, and sarilumab, with a focus on emerging drug classes and their distinct mechanisms of action. Results: Biologic DMARDs like abatacept, golimumab, and sarilumab offer hopeful treatment alternatives for patients who fail to respond to conventional therapies. However, individual outcomes differ because of the disease’s complexity and the influence of accompanying health conditions. Conclusions: Treating arthritis continues to be challenging due to its numerous underlying causes and the varied ways in which patients respond to treatment. Although biologics and targeted therapies have brought progress, additional research is needed to identify new treatment targets and enhance patient results. Full article

Memory cells are central to the adaptive immune system’s ability to remember and respond effectively to previously encountered pathogens. While memory cells provide robust protection against infections, they can also contribute to autoimmunity when regulation fails. Here, we review the roles of memory T and B cells in infection and autoimmunity, focusing on their differentiation, activation, effector functions, and underlying regulatory mechanisms. We elaborate on the precise mechanisms by which memory cells contribute to autoimmune diseases, highlighting insights from current research on how pathogenic memory responses are formed and sustained in autoimmunity. Finally, we explore potential therapeutic strategies aimed at modulating memory cells to prevent or treat autoimmune disorders, including B cell-depleting therapies (e.g., Rituximab), T cell-targeting agents (e.g., Abatacept), and cytokine inhibitors (e.g., IL-17 or IL-23 blockers) that are currently used in diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis. Full article

Morphea, also known as localized scleroderma, is an autoimmune chronic connective tissue disease. It is characterized by excessive collagen deposition in the dermis and/or subcutaneous tissue. The etiopathogenesis of this disease is not fully understood, with endothelial cell damage, immunological disorders, extracellular matrix disorders and factors such as infection, trauma and other autoimmune diseases being considered. As medicine advances, there is increasing evidence that genetic factors play a significant role in disease risk and progression. In addition to environmental factors and genetic predisposition, epigenetic factors may be potential triggers for morphea. Epigenetics studies changes that affect gene expression without altering the DNA sequence, such as microRNAs, long non-coding RNAs or DNA methylation. Understanding the pathogenesis of this disease is key to identifying potential new treatments. There are anecdotal reports of good therapeutic effects following the use of biological drugs such as tocilizumab, a humanized IgG monoclonal antibody; abatacept, a recombinant soluble fusion protein; JAK inhibitors, such as tofacitinib and baricitinib; and a drug used successfully in cancer treatment, imatinib, a tyrosine kinase receptor inhibitor. In this article, we aim to review up-to-date knowledge on the pathogenesis of morphea, with particular emphasis on genetic and epigenetic factors. In addition, we present the new options of morphea treatment based on several case series treated with new drugs that are potential targets for the development of therapies for this disease. Full article

Background/Objectives: Pulmonary fibrosis (PF) results in a progressive decline of lung function due to scarring. Drugs are among the most common causes of PF. The objective of our study was to reveal the structure of drugs involved in PF development. Methods: we performed a retrospective descriptive pharmacoepidemiologic study on spontaneous reports (SRs) with data on PF registered in the Russian National Pharmacovigilance database for the period from 4 January 2019 to 31 May 2024. Results: A total of 1308 SRs on PF were finally identified with patients mean age of 59.3 ± 23.4 years. Death was reported in 30.7% (n = 401) with mean age of 59.9 ± 13.8 years. In the structure of culprit drugs, the following groups were leaders: antineoplastic and immunomodulating agents (51.9%); systemic hormonal preparations, excluding sex hormones and insulins (7.4%); drugs affecting nervous system (7.1%); respiratory system (7.1%); alimentary tract and metabolism (6.5%); and cardiovascular system (5.5%). In the total sample, the top ten drugs were rituximab (5.5%), methotrexate (4.4%), etanercept (4.2%), leflunomide (4.0%), adalimumab (3.7%), tocilizumab (3.3%), abatacept (3.0%), alendronic acid (2.7%), secukinumab (2.6%), and infliximab (2.4%). The number of SRs per year nearly doubled from 2021 to 2022 and from 2022 to 2023 with a maximum peak expected for 2024. Conclusions: Our study demonstrated increased reporting on PF in the National Pharmacovigilance database from 2019 to 2024. We revealed outstanding results for the role of antineoplastic and immunomodulating agents in PF development. Full article

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA. Full article

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests. Full article

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major complication of rheumatoid arthritis (RA), but effective treatment remains an unmet need in its management. Our aim was to evaluate the therapeutic efficacy of abatacept for RA-ILD. Methods: This observational retrospective study included patients with RA-ILD treated with abatacept between 2012 and 2021. Indices of RA disease activity and interstitial lung disease (Disease Activity Score in 28 joints using C-reactive Protein [DAS28-CRP], Simplified Disease Activity Index [SDAI], Clinical Disease Activity Index [CDAI], serum Krebs von den Lungen-6 levels, % forced vital capacity [%FVC], and semi-quantified chest high-resolution computed tomography scores) were evaluated before and 1 year after the start of abatacept administration. Results: Overall, 38 patients were included. DAS28-CRP, SDAI, and CDAI were significantly improved (all with p < 0.0001). Total ground-glass opacity scores were decreased in both patients with usual interstitial pneumonia (UIP)-like patterns and with non-UIP-like patterns (p = 0.008 and <0.002, respectively). Total fibrosis scores were also decreased in the UIP-like pattern group (p < 0.042). The %FVC remained stable. Conclusions: Abatacept significantly improves RA disease activity and reduces pulmonary inflammation in patients with RA-ILD. Full article

The treatment of arteritic anterior ischemic optic neuropathy (AAION), non-arteritic ischemic optic neuropathy (NAAION), and posterior ischemic optic neuropathy (PION) is a topic of ongoing research with mixed evidence on some pharmacotherapies and a need for more consensus. This manuscript provides an overview of these conditions’ current, potential future, and attempted pharmacotherapies. AAION’s current treatment regimen consists of high-dose steroids, with methotrexate, tocilizumab, and abatacept, being the most viable steroid-sparing therapy candidates. As for NAAION, the treatments being tried are vast, with mixed evidence supporting each modality. Similarly, despite the various treatment options explored, there still needs to be a universally effective therapy for PION. More research is needed to formulate an agreed-upon treatment regimen for these conditions. Full article

Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent the standard prophylaxis in HLA-matched allogeneic stem cell transplantation (HSCT); other strategies focused on ATG, Post-Transplant Cyclophosphamide (PTCy), Abatacept and graft manipulation. Despite the high rate, first-line treatment for aGVHD is represented by corticosteroids, and Ruxolitinib is the standard second-line therapy; investigational approaches include Microbiota transplant and the infusion of Mesenchymal stem cells. GVHD is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. It is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. Extracorporeal Photopheresis (ECP) is still an option used for steroid refractoriness or to achieve a steroid-sparing. For Ruxolitinib-refractory cGVHD, Belumosudil and Axatilimab represent the most promising agents. Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments. Full article

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments. Full article

Giant cell arteritis (GCA) is a large-vessel vasculitis affecting elderly patients and targeting the aorta and its main branches, leading to cranial and extracranial manifestations. The mechanism behind the ischemia is a granulomatous-type inflammation with potentially critical lesions, including visual loss involving the ophthalmic artery. Despite significant progress in unraveling the pathophysiology of this disease, treatment options still rely on glucocorticoids (GCs) to overcome active vascular lesions and disease flares. However, uncertainty still revolves around the optimal dose and tapering rhythm. Few corticosteroid-sparing agents have proven useful in GCA, namely, methotrexate and tocilizumab, benefiting cumulative GC dose and relapse-free intervals. The future looks promising with regard to using other agents like abatacept and Janus-kinase inhibitors or blocking the granulocyte–macrophage colony-stimulating factor receptor. Full article