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PURPOSE: This review aims at investigating pathophysiological mechanisms in spondyloarthritis (SpA). Analysis of genetic factors, immunological pathways, and abnormalities of bone metabolism lay the foundations for a better understanding of development of the axial clinical manifestations in patients, allowing physician to choose the most appropriate therapeutic strategy in a more targeted manner. RECENT FINDINGS: In addition to the contribution of MHC system, findings emerged about the role of non-HLA genes (as ERAP1 and 2, whose inhibition could represent a new therapeutic approach) and of epigenetic mechanisms that regulate the expression of genes involved in SpA pathogenesis. Increasing evidence of bone metabolism abnormalities secondary to the activation of immunological pathways suggests the development of various bone anomalies that are present in axSpA patients. SpA are a group of inflammatory diseases with a multifactorial origin, whose pathogenesis is linked to the genetic predisposition, the action of environmental risk factors, and the activation of immune response. It is now well known how bone metabolism leads to long-term structural damage via increased bone turnover, bone loss and osteoporosis, osteitis, erosions, osteosclerosis, and osteoproliferation. These effects can exist in the same patient over time or even simultaneously. Evidence suggests a cross relationship among innate immunity, autoimmunity, and bone remodeling in SpA, making treatment approach a challenge for rheumatologists. Specifically, treatment targets are consistently increasing as new drugs are upcoming. Both biological and targeted synthetic drugs are promising in terms of their efficacy and safety profile in patients affected by SpA.
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Espondiloartritis Axial , Enfermedades Óseas Metabólicas , Osteoporosis , Espondiloartritis , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Biología Molecular , Aminopeptidasas , Antígenos de Histocompatibilidad MenorRESUMEN
Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.
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Artritis Reumatoide , Uveítis , Humanos , Antígeno HLA-B27/uso terapéutico , Reumatólogos , Antígeno HLA-B51 , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Derivación y Consulta , Italia/epidemiologíaRESUMEN
OBJECTIVES: Long-term quality of life (QoL) is significantly compromised in patients with psoriatic arthritis (PsA) and only partially improves achieving remission or low disease activity. The main aim of this study is to evaluate the QoL in PsA patients and to investigate their possible relationship with clinical remission and low disease activity, and with its duration over time. METHODS: A multicentre cross-sectional observational study has been performed. QoL domains considered were analysed through PROs. Chi2 test was used for analysis of contingency tables, while Mann-Whitney test and Kruskal-Wallis test with Holm's pairwise comparison corrections were used to compare ranks. To evaluate variables associated to the different QoL domains, univariate and multiple linear regressions were used. RESULTS: 143 participants were included in this study. The physical component of the Short Form-36 or Functional Assessment of Chronic Illness Therapy-Fatigue tends to improve with short duration of low or minimal disease activity. However, this is not confirmed for the mental component of SF-36 (MCS), which improved only with longer duration of low/minimal disease activity. CONCLUSIONS: This study proves the existence of an inverse relation between disease activity and QoL domains. Apart from low or minimal disease activity, also its persistence over time has a great influence on the patient's perception of their clinical condition; therefore, persistence over time of clinical remission/low disease activity should be added to the latest definition of treat-to-target in PsA.
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Antirreumáticos , Artritis Psoriásica , Antirreumáticos/uso terapéutico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Estudios Transversales , Humanos , Calidad de Vida , Índice de Severidad de la EnfermedadAsunto(s)
Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Eosinófilos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , InmunosupresoresRESUMEN
Background: Enteropathic spondyloarthritides (eSpAs) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. Objectives: We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics. Design: Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018-October 2019). Methods: We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine. Results: A total of 190 eSpA patients [118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA] were enrolled. axSpA patients had a higher prevalence of men sex, HLA-B27 positivity, uveitis and pancolitis compared with peripheral eSpA. Median diagnostic delay in eSpA was 48 months (IQR 6-77) with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA (median/IQR 36/17-129 versus 31/10-57 months, p = 0.03) and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. r-axSpA patients with sclerosis, syndesmophytes and bridge at CR had higher diagnostic delay than those without lesions. Men showed higher prevalence of spine damage lesions than women as sclerosis, squaring, syndesmophytes and bridges. Longer disease duration was detected in patients with radiographic damage as bridge and sacroiliitis grade 3. On MRI, sacroiliac bone oedema was associated with reduced diagnostic delay, whereas bone erosions were associated with higher diagnostic delay compared with that in patients without these lesions. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Conclusion: Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.
Diagnostic delay in patients affected by enteropathic spondyloarthritis Enteropathic Spondyloarthritides (eSpA) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical and radiographic characteristics. We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography and magnetic resonance images of sacroiliac joints/spine. 190 eSpA patients (118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA)) were enrolled. Median diagnostic delay in eSpA was 48 months with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.
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We aimed to identify an expression profile of lncRNAs potentially related to treatment response in Psoriatic arthritis (PsA) patients, to be used as potential genomic biomarkers predictors of drug treatment effectiveness. In addition, we evaluated a possible association between lncRNAs genetic variants and the response to therapy using the clinical parameter of Disease Activity Index. For the expression study, we collected 48 treated PsA patients, monitoring the treatment response for 12 months. We initially used PCR Array and, then, we validated the results with qRT-PCR. We also retrospectively genotyped 163 treated PsA patients. Firstly, we observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responders, also considering separately the single groups of patients treated with TNFi and IL17i. In addition, our results seem to highlight a potential dose-dependent effect of rs941576 (MEG3) variant allele on Disease Activity Index. Our study suggests a possible role of the lncRNA MEG3 in the treatment response to biological drugs.
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Artritis Psoriásica , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Biomarcadores , Polimorfismo de Nucleótido Simple , Interleucina-17/genética , Interleucina-17/metabolismo , Productos Biológicos/uso terapéutico , Antirreumáticos/uso terapéuticoRESUMEN
OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.
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Antirreumáticos , Enfermedades Inflamatorias del Intestino , Psoriasis , Espondiloartritis , Femenino , Humanos , Estudios Retrospectivos , Antirreumáticos/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Espondiloartritis/complicaciones , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/epidemiología , Psoriasis/epidemiología , Terapia Biológica/efectos adversosRESUMEN
The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.
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Antirreumáticos , Artritis Reumatoide , Inhibidores del Factor de Necrosis Tumoral , Humanos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/patología , Regiones Promotoras Genéticas , Receptores de Calcitriol/genética , Receptores de Calcitriol/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
OBJECTIVES: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations. METHODS: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected. RESULTS: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult. CONCLUSIONS: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases.
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Educación , Biopsia Guiada por Imagen , Ultrasonografía Intervencional , Humanos , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/patología , Inflamación , Muñeca/patología , Rodilla/patologíaRESUMEN
INTRODUCTION: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. METHODS: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. RESULTS: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. CONCLUSIONS: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.
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BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments' clinical response. Goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. OBJECTIVE: To investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors' according to RA patient characteristics in a real-world setting. METHODS: 718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. Patients failing to at least two csDMARDs or bDMARDs' drug for inefficacy were defined "csDMARDs multifailure" and "bDMARDs multifailure", respectively. Discontinuation of at least two cs- and bDMARDs was termed "global multifailure". RESULTS: In total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. Reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. Longstanding disease (≥ 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). Thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). CONCLUSIONS: Different causes of drug discontinuation were observed on DMARDs treatments. Demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets.
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Antirreumáticos , Artritis Reumatoide , Humanos , Masculino , Femenino , Antirreumáticos/efectos adversos , Centros de Atención Terciaria , Estudios Retrospectivos , Artritis Reumatoide/tratamiento farmacológico , Italia/epidemiologíaRESUMEN
Hughes-Stovin syndrome (HSS) is a rare potentially fatal vasculitis supposedly belonging to the spectrum of Behçet disease without ocular involvement. HSS tends to play by a temporal pattern, starting with thrombosis and followed by formation of pulmonary aneurysms. Since its mortality can reach 25% of cases, early recognition and appropriate therapy represent the major clinical challenges. We describe a rare case of HSS successfully treated via multidisciplinary management by an endovascular approach and immunosuppressive therapy.
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INTRODUCTION: Psoriatic arthritis (PsA) is a chronic arthritis typically associated with cutaneous psoriasis (PsO). Its pathogenesis is connected to an innate and acquired immune response, as well as genetic risk alleles. The extent of immunopathogenic mechanisms and the heterogenicity of clinical manifestation make the identification of patient-targeted therapies a critical issue, and the treatment decision challenging in patients' management. AREAS COVERED: This review includes a brief overview of biological and small-molecule therapies, focusing on evidence from clinical trials and real-world data that support their use in PsA. We summarize novel and future possible therapeutic strategies, the importance that comorbidities have on selection of therapy and discuss the adverse event of each drug. Relevant papers for up to 1 August 2022 (trials, real-life studies, and reviews) regarding biologics and/or small molecules were summarized. EXPERT OPINION: In recent years, the treatment of PsA has been revolutionized by new targeted therapies, which offer the opportunity to perform a tailored-tail management, considering risk factors, comorbidities, and the different PsA phenotypes. Growing experience with these new agents allows novel treatment approaches that may improve clinical outcomes for PsA patients, in terms of remission/low disease activity and quality of life.
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Artritis Psoriásica , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Calidad de Vida , Psoriasis/tratamiento farmacológicoRESUMEN
An accurate prediction of cardiovascular (CV) risk in patients with Axial Spondyloarthritis (axSpA) is a strong unmet need, as CV risk algorithms poorly perform in these subjects. The aim of this study was to establish whether the persistence of high C-reactive protein (CRP) and high disease activity may be considered predictive factors of CVD in axSpA. 295 patients without personal history of CVD, were consecutively enrolled in this study. To evaluate the relationship between CV events occurrence (fatal and non-fatal) and the persistence of increased CRP levels, ASDAS (Ankylosing Spondylitis Disease Activity Score) > 2.1, and BASDAI (Bath Ankylosing Spondylitis Disease Activity) > 4 during the follow-up, univariable and multivariable Cox Proportional Hazard Models have been performed. During follow-up (we analyzed 10-years retrospective data), 23 patients had a CV event. Multivariable Cox Proportional Hazard Models showed a strong association between CV event and the persistency of increased CRP levels (namely, percentage of visits in which CRP levels were increased) (HR = 1.03; 95%CI 1.015-1.045; p < 0.001), of ASDAS > 2.1 (HR = 1.014, 95%CI 1.000-1.028, p = 0.047), and of BASDAI > 4 (HR 1.019, 95%CI 1.006-1.033, p = 0.006) during follow-up, after adjustment for age, sex, and diabetes. This study suggests that persistence of increased CRP levels and high disease activity may be considered biomarkers to identify those axSpA patients at higher risk of CVD. Innovative axSpA-specific CV risk score, including these variables, have to be developed.
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Espondiloartritis Axial , Enfermedades Cardiovasculares , Espondiloartritis , Espondilitis Anquilosante , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/etiología , Humanos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/complicacionesRESUMEN
Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called "non-radiographic axial SpA" (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi). Several studies indicate that AS women have doubled risk to failure TNFi compared with males. This diversity in drugs' efficacy among women and men may be caused by differences in the balance of sex hormones and in gene-specific expression likely triggered by X-chromosome instability and gene-specific epigenetic modifications. Evidence reported that polymorphisms in microRNAs on X- and other chromosomes, such as miR-146a, miR-155, miR-125a-5p, miR-151a-3p and miR-22-3p, miR-199a-5p could be involved in the different clinical presentation of SpA, as well as disease activity. In addition, association with non-response to TNFi treatment and presence of IRAK3 and CHUCK genes in SpA patients was recently detected. Finally, polymorphisms in genes involved in IL-23/IL-17 pathway, such as in drug pharmacodynamics and pharmacokinetics may have a role in response to TNFi, IL17i, and IL23i. A major understanding of genomic variability could help in the development of new therapeutic targets or in taking advantages of different mechanisms of action of biological drugs. Moving from the multifactorial etiology of disease, the present review aims at evaluating genetic and epigenetic factors and their relationship with sex and bDMARDs response, helping to investigate the different expression among males and females of genes on X- and other chromosomes, as well as mi-RNA, to highlight relationships between sex and occurrence of specific phenotypes and symptoms of the disease. Moreover, the role of the epigenetic modification in relation to immune-regulatory mechanisms will be evaluated.
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ABSTRACT: Golimumab is a fully human monoclonal antibody against tumor necrosis factor (TNF) approved for the treatment of ulcerative colitis and not for Crohn disease (CD). Many CD patients experience primary, secondary failure, or intolerance to other TNF inhibitors (TNFi) approved in Italy for CD (adalimumab and infliximab). Spondyloarthritis (SpA) may be associated with CD (enteropathic, ESpA) in up to 50% of patients requiring a multidisciplinary and tailored approach. However, only few data from literature and no formal trials determined the efficacy and safety of golimumab in ESpA patients. We performed a case series on 12 patients affected by active CD and active ESpA were failure or intolerant to previous TNFi approved in Italy for both SpA and CD, infliximab and adalimumab. Golimumab was administered following rheumatologic dosage (subcutaneous 50âmg monthly; 100âmg monthly for patients ≥100âkg). Gastrointestinal and rheumatologic disease activity was evaluated with a follow-up of 2 years. A total of 9 patients were followed for 2 years of golimumab treatment. CD clinical activity ameliorated as shown by the reduction of Harvey-Bradshaw index and Crohn disease activity index (CDAI) at 12 and 24âmonths of treatment (Pâ=â.03 and Pâ=â.04, respectively) associated with reduction of C-reactive protein at 12 and 24âmonths (Pâ=â.04 for both comparisons) of treatment. SpA assessment revealed a significant reduction in tender joint count at 6 (Pâ=â.03), 12 (Pâ=â.03), and 24âmonths (Pâ=â.007) of treatment. Swollen joint count, pain, SpA disease activity, and disability reduced in several patients during the follow-up. No adverse events were registered in the follow-up. We demonstrate good clinical efficacy and safety profile of both gastrointestinal and rheumatologic involvement. This may indicate promising therapeutic option for ESpA patients affected by CD, and non-responsive to other TNFi.
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Anticuerpos Monoclonales/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Espondiloartritis/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Adulto , Anciano , Enfermedad de Crohn/complicaciones , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Espondiloartritis/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. METHODS: Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. RESULTS: DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. CONCLUSION: Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.
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Aborto Habitual/genética , Enfermedades Autoinmunes/genética , Antígenos HLA-DQ/genética , Infertilidad Femenina/genética , Micronutrientes/sangre , Aborto Habitual/epidemiología , Adulto , Alelos , Enfermedades Autoinmunes/epidemiología , Autoinmunidad , Biomarcadores/sangre , Femenino , Ferritinas/sangre , Ácido Fólico/sangre , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Infertilidad Femenina/epidemiología , Estado Nutricional , Embarazo , Factores de Riesgo , Vitamina B 12/sangre , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Rheumatoid arthritis (RA) and autoimmune thyroid disease (AITD) can occur in the same patient in the autoimmune polyglandular syndrome 2. The association of the two conditions has been recognized long-time ago and the prevalence of AITD in patients with RA and vice versa is well assessed. Geographical variation of AITD and related autoantibodies in RA patients is partly due to ethnic and environmental differences of the studied populations. The impacts of thyroid disorders on RA outcome and vice versa are still controversy. In both AITD and RA genetic susceptibility and environmental factors play a synergic role in the development of the diseases. In this review we aimed at investigating the association of AITD and thyroid autoantibodies with RA, the common pathogenic pathways, the correlation with RA disease activity, and influence of the treatment.
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Artritis Reumatoide , Enfermedades de la Tiroides , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Autoanticuerpos/inmunología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/patología , Humanos , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/patología , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/patologíaRESUMEN
BACKGROUND: Enteropathic spondyloarthritis (ESpA) and inflammatory bowel diseases (IBD) have high impact on physical and psychological health but health-related quality of life (HRQoL) has never been evaluated in ESpA patients. PURPOSE: Cross-sectional multidisciplinary study was performed to evaluate HRQoL, state of health, and well-being in IBD and ESpA patients. METHODS: Consecutive IBD and ESpA outpatients were enrolled. Disease activity, inflammatory parameters, function, and quality of life (EuroQol questionnaire) were assessed at visit time and compared with 12 months ago. RESULTS: Two hundred fifty-three IBD patients were evaluated. Ninety-five patients met inclusion criteria. ESpA was established in 65.3% IBD patients. Most ESpA patients had discreet or good health perception (65.3% and 22.5%, respectively), similar to IBD group (64.6% and 20.7%, respectively). In both groups, no patients had exceptional state of general well-being. Compared with previous 12 months, ESpA group showed improved state of health in 12% of patients, worsening in 28% and stable state of health in 60%. Similar results were obtained in IBD group. Emotional and psychological problems (anxiety, depression, and feeling of loneliness and isolation) were reported: In ESpA patients, these feelings were observed in 58.1%, 40.57%, and 29% of cases, respectively; IBD patients showed slightly lower percentage. More than half of ESpA and IBD patients reported an embarrassment about their condition and worry about disease's future progression and physical pain. CONCLUSIONS: Well-being, quality of life, and psychological problems were described in ESpA and IBD patients. Disease management should include also social, mental, and psychological impacts, in terms of QoL.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Espondiloartritis , Ansiedad/epidemiología , Ansiedad/etiología , Estudios Transversales , Humanos , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy typically associated with psoriasis (PsO). The pathogenesis is strictly related to the association among the presence of genetic risk alleles and innate and acquired immune response with dramatic consequences on bone remodeling. Clinically, PsA patients may present heterogenicity of articular and periarticular manifestations that may be associated with the presence of comorbidities making treatment decision challenging in patients management. The identification of patient-targeted therapies is still a critical issue. Actually, several biological and synthetic drugs are promising in terms of efficacy and safety profile. National and international treatment recommendations support clinicians in the decision of the best treatment, although they may have limits basically related to updates and different outcomes included in the clinical studies evaluated. The aim of this narrative review is therefore to give guidance for clinicians for PsA patients treatment. For this purpose, we evaluated evidence on biological therapies efficacy used for PsA treatment. Specifically, we reviewed data on biological therapies, Janus kinases (JAK) inhibitors, and drugs with a new mechanism of action that are part of the treatment pipeline. The concept of "switching" and "swapping" is also described, as well as data concerning special populations such as pregnant women and elderly patients.