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OBJECTIVES: To describe phenotypes and outcomes of extra-renal flares in SLE, to identify clusters of extra-renal flares based on baseline features, and to develop a machine learning (ML) tool capable of predicting 'difficult to treat' (D2T) flares. METHODS: Extra-renal flares that occurred in our cohort over the last five years with at least one year of follow-up were included. Baseline clinical variables were described and flares assigned to clusters. Attainment of remission and low disease activity state (LLDAS) at 12 months were compared. Flares were then considered 'D2T' in case of non-attainment of LLDAS at 6 and 12 months. Baseline features were used to train a ML model able to predict future D2T-flares, at admission. Traditional approaches were then compared with informatic techniques. RESULTS: Among 420 SLE patients of the cohort, 114 flares occurred between 2015 and 2021; 79 extra-renal flares, predominantly mucocutaneous (24.1%) and musculoskeletal (45.6%), were considered. After 12 months, 79.4% and 49.4% were in LLDAS and in remission, respectively, while 17 flares were classified as D2T (21.5%); D2T flares received a higher cumulative and daily dose of glucocorticoids. Among the clusters, cluster 'D' (mild-moderate flares with mucocutaneous manifestations in patients with history of skin involvement) was associated with the lowest rate of remission. Among clinical data, not being on LLDAS at 3 months was the unique independent predictor of D2T flares. CONCLUSIONS: Our clusterization well separates extra-renal flares according to their baseline features and may propose a new identification standard. D2T flares, especially refractory skin manifestations, are frequent in SLE and represent an unmet need in the management of the disease as they are associated with higher glucocorticoid (GC) dosage and risk of damage accrual. Our ML model could help in the early identification of D2T flares, flagging them to elevate the attention threshold at admission.
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Lúpus Eritematoso Sistêmico , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Glucocorticoides/uso terapêutico , Rim , Medição de Risco , Índice de Gravidade de DoençaRESUMO
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.
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Idiopathic inflammatory myopathies are a group of rare, autoimmune, diseases typically involving striate muscle and also variously affecting several other systems or organs, such as joints, skin, lungs, heart and gastrointestinal tract. IIM are mainly characterised by subacute onset and chronic course and are burdened by significant morbidity and mortality. Despite the rarity of these conditions, several efforts have been undertaken in the last years to better understand their pathogenesis, as well as to achieve a more precise classification and to define the optimal therapeutic approach. The aim of this review is to provide an up-to-date digest of the most relevant studies published on this topic over the last year.
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Doenças Autoimunes , Miosite , Humanos , Miosite/diagnóstico , Miosite/tratamento farmacológico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapiaRESUMO
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.
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Interação Gene-Ambiente , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Fatores de Risco , Predisposição Genética para Doença , Incidência , Exposição Ambiental/efeitos adversos , Meio AmbienteRESUMO
Systemic lupus erythematosus (SLE) is classically regarded as the landmark of systemic autoimmune diseases, characterised by protean, multi-systemic manifestations and a highly variable clinical course.Over the last years, both clinical and translational clinical research efforts led to significant steps forward in management and treatment of SLE. However, numerous aspects of SLE, from pathogenesis to treatment, still remain challenging, and several unmet needs persist for both patients and physicians. Following the previous annual reviews of this series, herewith, we aim to report the most relevant new updates on SLE, issued in 2023. In particular, we focused on biomarkers, clinical aspects and outcomes, comorbidities, as well as new treatment targets and real-world evidence.
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Lúpus Eritematoso Sistêmico , Médicos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Biomarcadores , ComorbidadeRESUMO
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of disorders in which chronic inflammation of the skeletal muscle, leading to muscle weakness, is a common feature. Different phenotypes have been identified within the IIM spectrum based on extra-muscular manifestations, immunology, muscle histology, responsiveness to therapy, and prognosis. The pathogenesis, classification, treatment, and prognosis of the different IIM subtypes are subject to active discussion and research. This review highlights the most relevant literature published on this topic over the last year.
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Miosite , Humanos , Músculo Esquelético/patologia , Prognóstico , Inflamação/patologiaRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. New data regarding pathogenic pathways, biomarkers and clinical manifestations of SLE are emerging, and new drugs and therapeutic protocols have been proposed to improve the control of disease activity. Furthermore, new insights into comorbidities and reproductive health in SLE patients are constantly emerging.This annual review aims to summarise the most relevant data on SLE that was published in 2022.
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Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Comorbidade , Biomarcadores/metabolismoRESUMO
OBJECTIVES: The differential diagnosis between idiopathic inflammatory myopathies (IIM) and muscular dystrophies (MD) may be challenging. We analysed the potential role of muscular magnetic resonance imaging (MRI) in the differential diagnosis between IIM and MD. METHODS: MRI of patients (91 IIM and 43 MD), studied with a standardised protocol, have been collected. The presence of oedema, muscular atrophy and intramuscular adipose changes were evaluated. Moreover, we computed a composite score for each MRI item to better discriminate between the two diseases. RESULTS: Oedema was significantly more prevalent in IIM compared with MD in pelvis muscles (p<0.001), anterior lodge and medial lodges (p=0.044) of the thighs. Adipose infiltration/substitution and muscular atrophy were more prevalent in MD, in particular adipose tissue was prevalent in all the compartments of the thighs (p<0.05), atrophy was prevalent at the thighs and pelvis muscles (p<0.001). The probability of IIM increased with higher oedema score and decreased with higher atrophy and intramuscular adipose infiltration/substitution scores. CONCLUSIONS: A different distribution of muscular involvement between IIM and MD has been identified. Muscular MRI may be useful in the differential diagnosis, potentially reducing the number of muscular biopsies that may be reserved only for doubtful cases.
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Doenças Musculares , Distrofias Musculares , Miosite , Humanos , Diagnóstico Diferencial , Doenças Musculares/diagnóstico , Miosite/diagnóstico , Distrofias Musculares/diagnóstico , Distrofias Musculares/patologia , Músculo Esquelético/patologia , Atrofia Muscular/diagnóstico , Atrofia Muscular/patologia , Imageamento por Ressonância Magnética/métodos , EdemaRESUMO
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare and complex connective tissue diseases, mainly characterised by inflammatory involvement of skeletal muscles. Several other organs may be affected, particularly lungs, heart, skin, gastrointestinal tract and joints, often determining the morbidity and mortality associated with these autoimmune disorders. The course is generally chronic and the onset subacute. This latter aspect, together with the rarity of these conditions, can result in a clinical challenge for the physician with a considerable diagnostic delay. The scientific literature makes continuous advances in the understanding of these diseases, in particular with regards to the pathogenesis, serological findings, diagnostic strategies and therapeutic approaches. The aim of this review is to highlight the most relevant literature contributions published on this topic over the last year.
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Doenças Autoimunes , Miosite , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Diagnóstico Tardio , Humanos , Pulmão/patologia , Músculo Esquelético/patologia , Miosite/diagnóstico , Miosite/terapiaRESUMO
Axial spondyloarthritides (axSpA) are a group of systemic inflammatory rheumatic diseases with a broad spectrum of clinical manifestations and typical imaging features, rarely accompanied by laboratory abnormalities. They can be classified into a so-called non-radiographic form (nr-axSpA), unlike the radiographic one, because magnetic resonance imaging may show specific inflammatory lesions when conventional radiology is not able to highlight them. Inflammatory involvement of the axial skeleton tends to associate typically with new bone formation and peripheral joints may also be affected. Patients with axSpA are at higher risk of developing some typical extraarticular manifestations, particularly, acute anterior uveitis, psoriasis and inï¬ammatory bowel disease. In this paper we review the literature on axSpA of 2019 and 2020 (Medline search of articles published from 1st January 2019 to 31st December 2020).
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Psoríase , Espondilartrite , Espondilite Anquilosante , Uveíte Anterior , Humanos , Imageamento por Ressonância Magnética , Espondilartrite/diagnóstico por imagemRESUMO
Protein sequence stores the information relative to both functionality and stability, thus making it difficult to disentangle the two contributions. However, the identification of critical residues for function and stability has important implications for the mapping of the proteome interactions, as well as for many pharmaceutical applications, e. g. the identification of ligand binding regions for targeted pharmaceutical protein design. In this work, we propose a computational method to identify critical residues for protein functionality and stability and to further categorise them in strictly functional, structural and intermediate. We evaluate single site conservation and use Direct Coupling Analysis (DCA) to identify co-evolved residues both in natural and artificial evolution processes. We reproduce artificial evolution using protein design and base our approach on the hypothesis that artificial evolution in the absence of any functional constraint would exclusively lead to site conservation and co-evolution events of the structural type. Conversely, natural evolution intrinsically embeds both functional and structural information. By comparing the lists of conserved and co-evolved residues, outcomes of the analysis on natural and artificial evolution, we identify the functional residues without the need of any a priori knowledge of the biological role of the analysed protein.
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Biologia Computacional , Proteínas/análise , Sequência de Aminoácidos , Modelos Moleculares , Conformação Proteica , Proteínas/metabolismoRESUMO
In this report we have tested a parallel implementation for the simulation of lipid bilayers at the atomistic level, based on a generalized ensemble protocol where only the torsional degrees of freedom of the alkyl chains of the lipids are heated. The results in terms of configurational sampling enhancement have been compared with a conventional simulation produced with a widespread molecular dynamics code. Results show that the proposed thermodynamic-based multiple trajectories parallel protocol for membrane simulations allows for an efficient use of CPU resources with respect to the conventional single trajectory, providing accurate results for area and volume per lipid, membrane thickness, undulation spectra and boosting significantly diffusion and mixing in lipid bilayers due to the sampling enhancement of gauche/trans ratios of the alkyl chain dihedral angles.
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Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , TermodinâmicaAssuntos
Doenças Autoimunes , COVID-19 , Doenças Reumáticas , Humanos , Vacinas contra COVID-19 , Vacinas de mRNARESUMO
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.
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Progressão da Doença , Lúpus Eritematoso Sistêmico , Doenças do Tecido Conjuntivo Indiferenciado , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças do Tecido Conjuntivo Indiferenciado/complicações , Doenças do Tecido Conjuntivo Indiferenciado/epidemiologia , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico , Estudos Longitudinais , Imunossupressores/uso terapêutico , Índice de Gravidade de Doença , Glucocorticoides/uso terapêuticoRESUMO
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.
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Lúpus Eritematoso Sistêmico , Qualidade de Vida , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Qualidade de Vida/psicologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Medidas de Resultados Relatados pelo Paciente , Depressão/psicologia , Depressão/epidemiologiaRESUMO
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.
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Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Humanos , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , PrescriçõesRESUMO
OBJECTIVES: To analyse the response to immunosuppressants (IS) in extrarenal flares of SLE to determine the most appropriate timing during follow-up for a change in therapeutic strategy. METHODS: Observational cohort study including a total of 81 patients with SLE with extrarenal flares requiring a change in IS over the period 2015-2022. Baseline clinical variables were described, and follow-up data at 1, 3, 6 and 12 months time-points were collected. RESULTS: Among patients flaring that achieved lupus low disease activity state (LLDAS5) at 12 months of follow-up, we identified two subgroups ('late responders' and 'early responders'), which showed no significant differences in demographic characteristics, baseline clinical data, cumulative dosage of glucocorticoids or type of IS. Cox model analysis revealed a significant association of a change in IS (p=0.019) and achieving LLDAS5. Contingency table analysis indicated a significant relationship (p=0.004) between IS change at 6 months and individuals achieving LLDAS5 and remission at 12 months. CONCLUSIONS: Our findings suggest that clinical improvement of extrarenal flares typically occurs within 6 months of initiating IS. This timeframe could represent an appropriate timing to evaluate the response in a treat-to-target approach in SLE.
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Imunossupressores , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Feminino , Masculino , Imunossupressores/uso terapêutico , Adulto , Pessoa de Meia-Idade , Fatores de Tempo , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Estudos de Coortes , Índice de Gravidade de Doença , SeguimentosRESUMO
Treat-to-target is a therapeutic approach based on adjustments to treatment at set intervals in order to achieve well-defined, clinically relevant targets. This approach has been successfully applied to many chronic conditions, and in rheumatology promising results have emerged for rheumatoid arthritis. For systemic lupus erythematosus (SLE), defining the most meaningful treatment targets has been challenging, due to disease complexity and heterogeneity. Control of disease activity, the reduction of damage accrual and the patient's quality of life should be considered as the main targets in SLE, and several new drugs are emerging to achieve these targets. This review is focused on describing the target to achieve in SLE and the methods to do so, and it is also aimed at discussing if treat-to-target could be a promising approach also for this complex disease.
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BACKGROUND: SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended. OBJECTIVES: To describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE. METHODS: Retrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up. RESULTS: 417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death. CONCLUSIONS: In our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fatores Sexuais , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Glucocorticoides/efeitos adversos , Progressão da DoençaRESUMO
Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.