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1.
Kidney Int ; 106(3): 369-391, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38844295

RESUMEN

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the pathophysiology, diagnosis, and management of various glomerular diseases, diabetic nephropathy, and other forms of hemolytic uremic syndrome. Conference participants reviewed the evidence for complement playing a primary causal or secondary role in progression for several disease states and considered how evidence of complement involvement might inform management. Participating patients with various complement-mediated diseases and caregivers described concerns related to life planning, implications surrounding genetic testing, and the need for inclusive implementation of effective novel therapies into clinical practice. The value of biomarkers in monitoring disease course and the role of the glomerular microenvironment in complement response were examined, and key gaps in knowledge and research priorities were identified.


Asunto(s)
Activación de Complemento , Humanos , Activación de Complemento/inmunología , Inactivadores del Complemento/uso terapéutico , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Biomarcadores/sangre , Síndrome Hemolítico Urémico Atípico/inmunología , Síndrome Hemolítico Urémico Atípico/terapia , Síndrome Hemolítico Urémico Atípico/diagnóstico , Glomerulonefritis/inmunología , Glomerulonefritis/terapia , Glomerulonefritis/diagnóstico , Progresión de la Enfermedad , Nefropatías Diabéticas/inmunología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/terapia , Congresos como Asunto , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Enfermedades Renales/inmunología , Enfermedades Renales/terapia , Enfermedades Renales/diagnóstico
2.
Curr Opin Rheumatol ; 36(1): 27-34, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37916482

RESUMEN

PURPOSE OF REVIEW: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV. RECENT FINDINGS: The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome. SUMMARY: Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.


Asunto(s)
Crioglobulinemia , Hepatitis C Crónica , Hepatitis C , Vasculitis , Humanos , Rituximab/uso terapéutico , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C/complicaciones , Vasculitis/tratamiento farmacológico , Vasculitis/etiología , Crioglobulinemia/etiología , Crioglobulinemia/complicaciones , Hepacivirus
3.
Ann Rheum Dis ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816065

RESUMEN

OBJECTIVES: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). METHODS: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. RESULTS: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. CONCLUSION: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.

4.
Rheumatology (Oxford) ; 63(7): 1772-1778, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949781

RESUMEN

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve.


Asunto(s)
Accesibilidad a los Servicios de Salud , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/terapia , Europa (Continente) , Salud Global
5.
Artículo en Inglés | MEDLINE | ID: mdl-38402539

RESUMEN

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38814802

RESUMEN

OBJECTIVES: Oral and genital ulcers are the hallmark manifestation of Behçet's disease (BD), significantly impacting patients' quality of life. Our study focuses on comparing the effectiveness and safety of TNF inhibitors (TNFis) and apremilast in controlling oral ulcers of BD, aiming to provide evidence-based guidance for physicians in selecting appropriate treatment modalities. METHODS: A retrospective analysis was performed on BD patients treated between December 2016 and December 2021 with TNFis or apremilast for refractory oral ulcers. The study assessed treatment response by the absence of oral ulcers at 3 and 6 months, with additional evaluations for genital ulcers and articular involvement. RESULTS: The study included 78 patients, equally allocated between TNFis and apremilast treatments. Both groups showed significant oral ulcer reduction at 3 (p< 0.001) and 6 months (p= 0.01) with no significant difference between the treatments. Apremilast had a notable corticosteroid-sparing effect by the 3-month follow-up, persisting through 6 months. Both treatments were equally effective in reducing genital ulcers, with TNFis showing greater effectiveness in addressing articular involvement. Apremilast had a higher discontinuation rate due to gastrointestinal side effects. CONCLUSION: TNFis and apremilast are both effective for treating BD refractory oral ulcers. While TNFis may offer broader benefits for other disease manifestations, apremilast is distinguished by its corticosteroid-sparing effect, especially for patients with a milder disease phenotype. Treatment selection should consider individual disease severity and clinical features to ensure a personalized and effective management strategy.

7.
J Rheumatol ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38879188

RESUMEN

OBJECTIVE: Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy. METHODS: Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed. RESULTS: Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration (P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs (P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed (P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion (P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature. CONCLUSION: We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy.

8.
J Rheumatol ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38950957

RESUMEN

OBJECTIVE: To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE). METHODS: The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score (P = 0.01), and physician global assessment (P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P < 0.001) and in tender (P = 0.03) and swollen (P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders. CONCLUSION: This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

9.
Clin Exp Rheumatol ; 42(5): 1104-1114, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38743446

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. SLE pathogenesis is the result of complex interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal and environmental factors, and several aspects of these multifactorial connections are still unclear. Overall, for the disease development, an environmental trigger may induce immunological dysfunction in genetically predisposed individuals. This review aims to summarise the most relevant data on the impact of environmental factors on the incidence of SLE and on disease activity and damage in patients with an established diagnosis of SLE.


Asunto(s)
Interacción Gen-Ambiente , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/diagnóstico , Factores de Riesgo , Predisposición Genética a la Enfermedad , Incidencia , Exposición a Riesgos Ambientales/efectos adversos , Ambiente
10.
Clin Exp Rheumatol ; 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38855958

RESUMEN

Behçet's syndrome (BS) is a rare multisystem vasculitis involving blood vessels of any size. BS aetiology is still unclear to date, and the heterogeneity of clinical expression among ethnics and genders make early diagnosis challenging. However, so far, considerable efforts have been made toward the understanding of BS, leading researchers to agree that the coexistence of some environmental triggers and a genetical susceptibility both underlie BS aetiopathogenesis. In particular, viral agents, oral microbial flora, and mucosal microbiota have been widely explored in this regard, but still no specific microorganism has been definitely linked to the disease aetiology. Likewise, the concept that some environmental factors may play a role in BS clinical presentation has emerged based on the growing evidence that disease severity is usually higher in male patients, and that diet and fatigue may be involved in disease recurrence, especially in mucocutaneous manifestations. Moreover, smoke cessation is acknowledged as a risk factor for oral ulcerations, although the underlying mechanism is still not clear. All those environmental factors play their effects through epigenetic mechanisms. The aim of this review is to discuss the evidence on the role of environmental factors in BS aetiopathogenesis and clinical course.

11.
Clin Exp Rheumatol ; 42(7): 1321-1332, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38976289

RESUMEN

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Fumar Tabaco , Humanos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Factores de Riesgo , Fumar Tabaco/efectos adversos , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Pronóstico , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/epidemiología , Medición de Riesgo , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/etiología , Biomarcadores/sangre
12.
Clin Exp Rheumatol ; 42(5): 1075-1082, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38149633

RESUMEN

OBJECTIVES: The COVID-19 outbreak led to an increase in mental disorders, particularly post-traumatic stress disorder (PTSD), in the general population and especially in high-risk populations such as patients with rheumatologic conditions. Although these latters are considered vulnerable to developing PTSD, few specific data have been particularly reported in the framework of the pandemic. The aim of the present study was to investigate PTSD and post-traumatic stress symptoms (PTSS) in a sample of patients with systemic autoimmune disease (SAD), followed in the framework of a prospective observational study during the pandemic. METHODS: The PERMAS project is a prospective observational study including patients with SAD and involving the Rheumatology and the Psychiatric Clinics of the Azienda Ospedaliero Universitaria Pisana (AOUP, Pisa, Italy) and the Institute of Management of the Scuola Superiore Sant'Anna (Pisa, Italy). The assessments included: a data-sheet for sociodemographic and clinical characteristics; the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), for PTSD and PTSS; the 36-item Short Form Survey (SF-36) to assess quality of life. RESULTS: The total sample consisted of 252 patients with SAD, including 131 with connective tissue disease, 101 with arthritis and 20 with systemic vasculitis. The diagnostic groups differed significantly in age (p<0.001), gender (p<0.001), prevalence of full-blown and partial PTSD (p=0.001), and other psychopathologic variables. Connective tissue disease and SF-36 were significantly associated with the TALS-SR scores in both univariate (p<0.001) and multivariate (p<0.025; p<0.001) analyses. CONCLUSIONS: Patients with SAD, and, in particular, patients with connective tissue diseases reported an increased risk of developing stress-related psychopathological symptoms, indicating the need for special psychological monitoring of this high-risk group.


Asunto(s)
Enfermedades Autoinmunes , COVID-19 , Calidad de Vida , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Masculino , Femenino , COVID-19/psicología , COVID-19/epidemiología , Persona de Mediana Edad , Enfermedades Autoinmunes/psicología , Enfermedades Autoinmunes/epidemiología , Estudios Prospectivos , Adulto , Italia/epidemiología , Anciano , Factores de Riesgo , SARS-CoV-2 , Prevalencia
13.
Int J Mol Sci ; 25(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39000379

RESUMEN

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.


Asunto(s)
Azetidinas , Tratamiento Farmacológico de COVID-19 , COVID-19 , Quimioterapia Combinada , Unidades de Cuidados Intensivos , Metilprednisolona , Purinas , Pirazoles , SARS-CoV-2 , Sulfonamidas , Humanos , Purinas/uso terapéutico , Purinas/administración & dosificación , Masculino , Femenino , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , COVID-19/mortalidad , COVID-19/complicaciones , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/administración & dosificación , Resultado del Tratamiento , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/administración & dosificación
15.
RMD Open ; 10(2)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38670557

RESUMEN

OBJECTIVES: Undifferentiated connective tissue diseases (UCTDs) are systemic autoimmune conditions that cannot be diagnosed nor classified as defined CTD; the majority maintains an undifferentiated profile (stable UCTD, sUCTD) over time. Data on long-term outcomes of sUCTD are lacking. METHODS: Retrospective longitudinal analysis of an inception cohort of 141 patients with sUCTD.Disease evolution and damage accrual were evaluated at 1, 5 and 10 years. Partial least square (PLS) regression was used to identify the basal variables contributing to damage accrual at 1, 5 and 10 years of follow-up. Trend of damage over time was compared with a cohort of age-matched and sex-matched patients with systemic lupus erythematosus (SLE) by means of Nelson-Aalen analysis. RESULTS: 11.3% of patients evolved to a definite CTD after a median 11 years (IQR 6-25) from the first symptom. At last visit, 10% were on glucocorticoids and 6% on immunosuppressive therapy. In 27.3%, at least one item of organ damage was recorded according to the SLICC/DI score (mean score 1.19±0.46). At PLS analysis, age at diagnosis and age at first symptoms were related to damage at 1 year, not taking antimalarials and taking immunosuppressants were associated with damage at 5 years.The mean survival without damage was 9.3 years in sUCTD and 8.4 years in SLE. The 10-year probability without damage was 62% and 23% in SLE and sUCTD, respectively (p=0.015). CONCLUSIONS: Although less significantly impacted than in patients with SLE, in the long-term UCTDs can accumulate organ damage and evolve into defined connective tissue diseases.


Asunto(s)
Progresión de la Enfermedad , Lupus Eritematoso Sistémico , Enfermedades Indiferenciadas del Tejido Conectivo , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedades Indiferenciadas del Tejido Conectivo/complicaciones , Enfermedades Indiferenciadas del Tejido Conectivo/epidemiología , Enfermedades Indiferenciadas del Tejido Conectivo/diagnóstico , Estudios Longitudinales , Inmunosupresores/uso terapéutico , Índice de Severidad de la Enfermedad , Glucocorticoides/uso terapéutico
16.
Lupus Sci Med ; 11(2)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39074950

RESUMEN

OBJECTIVE: To assess the impact of different disease activity patterns-long quiescent (LQ), chronically active (CA) and relapsing-remitting (RR)-on health-related quality of life (HRQoL) in a cohort of patients with systemic lupus erythematosus (SLE). METHODS: A retrospective, monocentric analysis of prospectively collected data. Adult SLE outpatients were enrolled between 2017 and 2021.For each year of follow-up, three disease activity patterns were defined: LQ if at each visit clinical Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Activity Index (SELENA-SLEDAI)=0, Physician Global Assessment (PGA)=0; CA if at each visit clinical SELENA-SLEDAI >0, PGA >0; RR if patients presented active disease in at least one visit during the observation period, interspersed with periods of remission. These patterns were applied to the year and the 3 years before enrolment.At enrolment, each patient completed: Short Form 36 (SF-36), Lupus Impact Tracker, Functional Assessment of Chronic Illness Therapy (FACIT), Hospital Anxiety and Depression Scale (HADS). The correlation between disease patterns and Patient-Reported Outcomes was analysed. RESULTS: 241 SLE patients were enrolled, of which 222 had complete clinical data for the 3-year period before enrolment. Both in the year and during the 3 years before enrolment, the most frequent disease pattern was the LQ (154/241 and 122/222 patients, respectively), followed by RR (53/241 and 92/222 patients, respectively) and CA (34/241 and 8/222 patients, respectively).At baseline, fibromyalgia, organ damage, age and daily glucocorticoid dose were associated with worse HRQoL.At the multivariable analysis, after adjusting for confounding factors, patients with LQ disease during the 3 years before enrolment presented a better physical HRQoL (SF-36 physical component summary, regression coefficient=3.2, 95% CI 0.51-5.89, p=0.02) and minor depressive symptoms (HADS-D, regression coefficient=-1.17, 95% CI -2.38 to 0.0.27, p=0.055), compared with patients with CA/RR disease. CONCLUSION: A persistently quiescent disease may have a positive impact on patients' physical HRQoL and on depressive symptoms. However, this condition appears insufficient to obtain a significant improvement in mental health, fatigue and disease burden among patients with SLE.


Asunto(s)
Lupus Eritematoso Sistémico , Calidad de Vida , Humanos , Lupus Eritematoso Sistémico/psicología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Calidad de Vida/psicología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Medición de Resultados Informados por el Paciente , Depresión/psicología , Depresión/epidemiología
17.
Clin Exp Med ; 24(1): 62, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38554250

RESUMEN

Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs-including age-and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Cardiovasculares , Inhibidores de las Cinasas Janus , Humanos , Anciano , Inhibidores de las Cinasas Janus/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Artritis Reumatoide/tratamiento farmacológico , Factores de Riesgo de Enfermedad Cardiaca , Antirreumáticos/efectos adversos
18.
RMD Open ; 10(2)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609320

RESUMEN

OBJECTIVE: The objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit. RESULTS: From 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years. CONCLUSIONS: Our data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Lupus Eritematoso Sistémico , Humanos , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Prescripciones
19.
Clin Rheumatol ; 43(2): 657-665, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38135860

RESUMEN

INTRODUCTION: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. METHODS: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). RESULTS: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). CONCLUSIONS: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Piperidinas , Pirimidinas , Humanos , Antirreumáticos/efectos adversos , Estudios Retrospectivos , Inhibidores de las Cinasas Janus/efectos adversos , Artritis Reumatoide/diagnóstico , Pirroles/efectos adversos , Medición de Resultados Informados por el Paciente , Resultado del Tratamiento
20.
J Pers Med ; 14(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39063966

RESUMEN

BACKGROUND: According to recent data, the age of patients could represent an important risk factor for MACE (major cardiovascular events), cancer, and VTE (venous thromboembolism) during treatment with JAK inhibitors in rheumatoid arthritis. We decided to analyze the population involved in the ReLiFiRa study by identifying two groups of patients: 65 years or more and less than 65 years of age, evaluating the efficacy and tolerability of 200 mg of Filgotinib daily. METHODS: Of the 120 ReLiFiRa patients, 54 were younger than 65 years old and 66 patients were 65 years old or older. The data of efficacy and tolerability of treatment with FIL 200 mg daily for 6 months were evaluated. RESULTS: After six months of treatment, FIL was effective in both age groups. In both groups, the median values of steroid DAS28, CDAI, ERS, PCR, tender joints, swollen joints, VAS, HAQ, PGA patients, and PGA physicians were reduced with a statistically significant difference comparing these values with the baseline values. The difference in age did not impact the effectiveness of the drug. The lipid profile data also did not demonstrate significant differences between the two age groups; however, the comparison between younger vs. older patients' populations regarding the total cholesterol/HDL ratio and LDL/HDL ratio shows a statistically significant difference: total cholesterol/HDL 3.4 (2.12-3.66) vs. 3.64 (3.36-4.13) p = 0.0004, LDL/HDL 1.9 (0.98-2.25) vs. 2.41 (2.04-2.73) p = 0.0002. There are no differences regarding the atherogenic index (LDL-C/HDL-C) and coronary risk index (TC/HDL-C) compared to baseline. CONCLUSIONS: After six months of treatment with FIL, the older population group showed a higher level of LDL and a lower level of HDL compared to younger patients. The atherogenic index and coronary risk index are higher in patients aged ≥ 65 years, but interestingly, there were no differences when comparing the 6-month data to baseline values. This condition highlights the impact of typical risk factors that act independently of treatment with Filgotinib.

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