Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

New onset and flare of rheumatic diseases following COVID-19 vaccination are mild and respond well to treatment: 9-month follow-up data from a single centre cohort.

OBJECTIVES: Anti-COVID-19 vaccines have proved to be effective and well tolerated. Great attention is now being paid to the characterisation of possible adverse events associated to their administration. We report a case series of suspected rheumatic diseases (RDs) following anti-COVID-19 vaccination. METHODS: We included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padova University Hospital between May and September 2021 presenting with a RD within 30 days after an anti-COVID-19 vaccine dose. Our selection was in accordance with the World Health Organisation guidelines for adverse event following immunisation (AEFI) surveillance. Patients were regularly re-evaluated by telemedicine or face-to-face visit. RESULTS: We identified 30 cases of RD following vaccination: 24 (80.0%) new onsets and 6 (20.0%) flares. Most of patients (76.6%) received the BNT162b2 vaccine. The mean time to RD onset/flare was 12±9 days. The most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (33.3%) and adult-onset Still's disease (13.3%). At the last FU visit (9.6±2.2 months), 83.3% of patients showed complete response to first- or second-line therapy, 13.3% a partial response and one patient (3.3%) was still experiencing an active disease. CONCLUSIONS: Considering the amount of vaccine doses administered during the evaluation period we overall detected a limited number of cases. We noted a clear prevalence of autoinflammatory conditions and seronegative manifestations. The great majority of patients had mild features and showed a good response to therapy.

Fetuin-A: A Novel Biomarker of Bone Damage in Early Axial Spondyloarthritis. Results of an Interim Analysis of the SPACE Study.

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8-18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7-215.9) vs. 239.9 (217.9-286.9), respectively, p < 0.001) and at T24 (207.6 (182.5-246.5) vs. 261.1 (210.2-286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (ß -0.5, p < 0.001) and at T24 (ß -0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage.

Psoriasis and imaging progression in early axial spondyloarthritis: results from a 48-month follow-up (Italian arm of SPACE study).

OBJECTIVES: To assess the influence of psoriasis on spinal/pelvic radiographic progression and MRI features in early-stage axial spondyloarthritis (axSpA). METHODS: Analysis of baseline data from the Italian SPACE cohort, including patients with chronic back pain (CBP; duration ≥3 months and ≤2 years; onset <45 years) was performed. Patients underwent a diagnostic work-up, including MRI and X-rays of the sacroiliac joints (SIJ), to establish diagnosis of axSpA (Assessment of Spondyloarthritis International Society criteria). Clinical features, disease activity and functional indices, imaging were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRIs were scored by two readers following Spondyloarthritis Research Consortium of Canada score, Stoke Ankylosing Spondylitis Spinal Score System modified by Creemers and modified New York criteria. Characteristics of axSpA patients with/without psoriasis were compared over time with descriptive statistics; multivariate logistic regression model was constructed to assess predictors of spinal/pelvic radiographic progression. RESULTS: Eighty-eight patients had axSpA (84.1% non-radiographic; 15.9% radiographic); 36.4% had psoriasis. Patients with psoriasis were older; less frequently had HLA-B27+ and radiographic sacroiliitis with unilateral/asymmetric pattern and more signs of spondylitis. Functional and disease activity indices decreased with slightly higher BASDAI and BASFI in axSpA with psoriasis. All patients showed slight spinal/pelvic radiographic progression. Patients without psoriasis showed increased sacroiliitis progression and low-grade spinal progression. More inflammatory corner lesions on cervical/thoracic MRI-spine were observed in patients with psoriasis. A significant downtrend of SPARCC SIJ/spine scores in all patients was found. Psoriasis was a predictor of increased spinal progression (odds ratio = 0.18; 95% CI: 0.04, 0.78). CONCLUSIONS: Psoriasis was associated with distinct axSpA features, increased spinal radiographic progression and low-grade radiographic sacroiliitis.

Subclinical enthesopathy of the midfoot: could it be a peculiar feature in early psoriatic arthritis?

OBJECTIVES: Bone scintigraphy (BS) is a sensitive tool that provides functional imaging to evaluate bone abnormalities in psoriatic arthritis (PsA). Our aims were to analyse the prevalence of increased BS uptake in the midfoot of PsA patients and to evaluate whether BS midfoot abnormalities could herald ultrasonography (US) and x-ray lesions in the same site. METHODS: Out of 88 consecutive BS performed in patients with early musculoskeletal symptoms (January-December 2010) and retrospectively analysed, 32 exams were carried out on subjects 3 months after being diagnosed with PsA. These patients were included in a retrospective study and analysed for BS feet uptake. Their baseline x-rays of the feet were also retrieved. Five years after BS (January-December 2015) all 32 PsA patients underwent clinical evaluation, x-rays and US of the feet. Frequency and percentage of each imaging abnormality of the midfoot were analysed. Clinical, functional and laboratory indexes were collected and correlations between clinical and imaging parameters were studied. RESULTS: Of all 32 PsA patients, 21 (65.6%) had an increased BS uptake in the midfoot, without any baseline x-ray abnormalities. After 5 years, the x-rays and US were able to detect ≥1 lesion in the midfoot of 14/32 (43.8%) and 28/32 (87.5%) patients, respectively. A high prevalence of enthesophytes in all 64 midfeet was shown by both x-rays (40.6%) and US (81.6%). We found a higher prevalence of structural lesions in the subgroup with BS positive midfoot compared with BS negative patients: x-rays [10/21 (47.6%) vs. 4/11 (36.4%); p=0.04] and US [19/21 (90.5%) vs. 8/11 (72.7%); p=0.04]. CONCLUSIONS: Midfoot involvement is frequent in PsA. BS increased uptake in the midfoot seems to be an early sign of the disease.

Fertility issues in women of childbearing age with spondyloarthritis.

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

INTRODUCTION: Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. METHODS: We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. RESULTS: Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. CONCLUSION: In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Assessment of Neuropathic Pain in Erosive Hand Osteoarthritis.

Background/Objectives: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis (OA) and a severely disabling condition. Patients affected by OA frequently lament symptoms suggestive of neuropathic pain (NP). The aim of our study was to ascertain the presence and severity of NP in patients with EHOA and correlate its presence with EHOA clinical characteristics. Methods: In this retrospective study, we included all consecutive EHOA patients with NP symptoms who underwent upper limb electroneurography (ENoG) and nerve ultrasound. The presence of NP was screened using the ID pain neuropathic pain-screening questionnaire (ID-Pain). In addition, the following NP questionnaires were also used: Douleur Neuropathique en 4 Questions (DN4), PainDETECT, and Neuropathic Pain Symptom Inventory (NPSI). Moreover, patients completed the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Dreiser's algofunctional finger index questionnaires assessing EHOA disease activity. The following clinical and laboratory data were collected: age, sex, BMI, disease duration, intensity of pain (VAS 0-10), painful and swollen joints, and inflammatory indices, as well as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Of the 34 patients studied, 24 (70.6%) presented NP to the ID-Pain questionnaire. According to DN4, 14 (41.2%) patients had NP, while using the PainDETECT questionnaire, 67.6% had NP. Patients with NP were statistically younger and had a higher VAS pain score compared to subjects without NP. The ENoG and median nerve ultrasound were normal in 81% of patients, while four patients had carpal tunnel syndrome. The ID-Pain questionnaire correlated with the number of painful joints (r = 0.48, p = 0.03) and with the AUSCAN questionnaire (r = 0.37, p = 0.05). The DN4 questionnaire correlated with PainDETECT (r = 0.58, p < 0.01). The PainDETECT questionnaire correlated with VAS pain (r = 0.49, p = 0.02), the DN4 questionnaire (r = 0.58, p < 0.01), and AUSCAN (r = 0.51, p = 0.02). The NPSI questionnaire correlated negatively with BMI (r = -0.53, p = 0.01) and positively with the PainDETECT questionnaire (r = 0.49, p = 0.02). Conclusions: Our study revealed that 32% to 70% of EHOA patients exhibited symptoms consistent with NP, with observed variability depending on the questionnaire utilized. Despite patients frequently exhibiting symptoms compatible with NP, only 19% of patients presented alterations on ENoG and ultrasound examinations confirming CTS. This suggests a probable nociplastic component for pain in patients with EHOA, which warrants tailored treatment. In the present study, NP correlated with clinical and functional indices of EHOA.

The impact of diet on disease activity in spondyloarthritis: A systematic literature review.

OBJECTIVES: Our study aimed to systematically review the evidence about the effect of diet or dietary supplements on spondyloarthritis (SpA) disease activity. METHODS: a systematic literature review (SLR) was conducted in MEDLINE, EMBASE, Cochrane and SCOPUS according to the "PEO" format (Population, Exposure, Outcome). The population was SpA (axial or peripheral, axSpA/pSpA, including Psoriatic Arthritis-PsA); the intervention any kind of diet/dietary supplement; the outcome disease activity. Inclusion criteria were: adult patients, Randomized Controlled Trials (RCTs) and longitudinal studies (so that a pre-and post-intervention assessment were available), papers in English. Risk of bias (RoB) was conducted with different tools according to the design of the study. RESULTS: Literature search yielded 1390 publications, of which 15 were finally inlcuded: 12 interventional and 3 observational studies. Among those with the lower RoB: a) 2 RCTs, one at unclear and one at low RoB, failed to show benefit of probiotics in SpA b) Two RCTs at unclear RoB provided evidence that weight loss, but not hypocaloric diet, was associated to MDA achievement in PsA. The remaining interventional studies were at high RoB. Among the observational studies, one study on Mediterranean diet demonstrated an association between diet adherence and a ≥ 20% decrease of ASDAS in axSpA. The other two observational studies were judged of poor quality. CONCLUSIONS: weight loss seem to be able to impact disease activity in PsA, while probiotics do not seem useful in SpA; evidence for dietary behaviors is scarce and heterogeneous.

Treat-to-target in real-life psoriatic arthritis patients: achieving minimal disease activity with bDMARDs/tsDMARDs and potential barriers.

OBJECTIVE: (1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to examine frequency and predictors of low disease activity (LDA) in patients with axial involvement (axPsA). METHODS: consecutive PsA patients in stable biological/targeted-synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs/tDMARDs) who attended our center were enrolled. Disease activity indices, including MDA and ankylosing spondylitis disease activity score-LDA (ASDAS-LDA) for axPsA, were evaluated at baseline and every 6 months, up to 36 months or bDMARDs/tsDMARDs discontinuation. Patients' history, BMI, comorbidities - including osteoarthritis (OA) and fibromyalgia - were collected. Variables were compared between patients who achieved sustained MDA and those who did not. Multivariable generalized estimating equation (GEE) models were built to identify predictors of MDA and ASDAS-LDA over time. Data were expressed as beta coefficient (95%CI). RESULTS: 104 patients were enrolled, 54% males, mean age 55.7 years; 52% had axPsA. Across all evaluations, 52-61% reached MDA, and 17-24% achieved ASDAS-LDA. AxPsA, fibromyalgia, OA and BMI≥35 were less frequently observed in patients with sustained MDA. The GEE model confirmed the following factors were significantly and independently associated with MDA: age (Beta=-0.05), bDMARDs/tsDMARDs duration (Beta=+0.31), axPsA (Beta=-1.07), fibromyalgia (Beta=-3.35), OA (Beta=-1.87), BMI≥35 (Beta=-2.53). Age (Beta=-0.01), fibromyalgia (Beta=-2.03) and OA (Beta=-1.30) were also independently associated with ASDAS-LDA. CONCLUSIONS: MDA is an attainable target in real-life. AxPsA represents a difficult-to-treat subset. Sustained MDA depends on disease features (axPsA) as well as patients' characteristics (e.g. age, bDMARDs/tDMARDs duration, comorbidities).

Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies.

Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient's subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA-IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4ß7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA-IBD.

The impact of SARS-CoV-2 infection and vaccination on inflammatory arthritis: a cohort study.

Objectives: To investigate the effects of SARS-CoV-2 infection, as well as short- (within 48 hours) and long-term (within 30 days) adverse events (AEs) of SARS-CoV-2 vaccines, including arthritis flares in a large cohort of patients with inflammatory arthritis (IA). Methods: A retrospective cohort study comprising 362 patients: 94 (26%) rheumatoid arthritis, 158 (43.6%) psoriatic arthritis and 110 (30.4%) ankylosing spondylitis; and 165 healthy controls (HC) to ascertain the prevalence and severity of SARS-CoV-2 infection in patients with IA, the rate of AEs associated with SARS-CoV-2 vaccines and disease flares within a month of the vaccination. All patients provided informed consent and data about SARS-CoV-2 infection and/or vaccination status. Results: One-hundred-seventeen (32.3%) patients and 39 (23.6%) HC were affected by SARS-CoV-2 infection. Forty (34.2%) patients experienced an IA flare within one month of infection, of whom 3 (7.5%) needed to switch therapy. The prevalence of SARS-CoV-2 infection, disease severity, and hospitalization rate were not significantly different. At least one shot of SARS-CoV-2 vaccine was administered in 331 (91.4%) patients and 147 (89.1%) HC. Within 48 hours, 102 (30.8%) patients developed vaccine-related AEs; 52 (15.7%) patients with >1 vaccine dose experienced an IA flare-up, of whom 12 (23.1%) needed to switch therapy. Conclusions: A significantly higher rate of IA flare was observed among patients who contracted SARS-CoV-2 infection vs. those without infection. Patients with IA experienced flares after SARS-CoV-2 vaccination, though it was not statistically significant.

The Genetic Contribution to Drug Response in Spondyloarthritis: A Systematic Literature Review.

Objective: Spondyloarthritis (SpA) are a group of diseases with a high heritability, whose pathogenesis is strongly determined by an interplay between genetic and environmental factor. Therefore, the aim of our study was to determine whether genetic variants could also influence response to therapy in SpA. Methods: A systematic literature review (SLR) was conducted in PubMed and Web of Science core collection, without publication-year restrictions (Last search 8th April 2021). The search strategy was formulated according to the PEO format (Population, Exposure, Outcome) for observational studies. The population was adult (≥18 years) patients with SpA. The exposure was inheritable genetic variations of any gene involved in the disease pathogenesis/drug metabolism. The outcome was response to the drug, both as dichotomous (response yes/no) and as continuous outcomes. Exclusion criteria were: (1) languages other than English, (2) case series, case reports, editorials, and reviews, (3) studies reporting genetic contribution to drug response only limited to extra-musculoskeletal features of SpA, (4) epigenetic modifications. Quality of the included study was independently assessed by two authors. Results: After deduplication, 393 references were screened by two authors, which led to the final inclusion of 26 articles, pertinent with the research question, that were considered for qualitative synthesis. Among these, 10 cohort, one cross-sectional, and five case-control studies were considered of at least good quality according to Newcastle-Ottawa Scale (NOS). In studies about TNF-blockers therapy: (1) polymorphisms of the TNF receptor superfamily 1A/1B (TNFRSF1A/1B) genes were most frequently able to predict response, (2) -238 and -308 polymorphisms of TNFα gene were studied with conflicting results, (3) TNFα polymorphism rs1799724, rs1799964, -857, -1,013, +489 predicted drug response in non-adjusted analysis, (4) PDE3A rs3794271 had a linear relationship with DAS28 reduction after anti-TNFα therapy. DHFR polymorphism +35,289 was able to predict response to methotrexate. Conclusions: Our SLR highlighted the existence of a genetic component in determining drug response. However, further studies are warranted to better define quantify it.

SARS-CoV-2 Infection in Spondyloarthritis Patients Treated With Biotechnological Drugs: A Study on Serology.

Objective: Serology could help to define the real extent of SARS-CoV-2 diffusion, especially in individuals considered at higher risk of COVID-19, such as spondyloarthritis (SpA) patients undergoing immunosuppressant. Our aim was to detect, by serology, previous SARS-CoV-2 contact in SpA, compared to health care workers (HCW), and healthy controls. Methods: Sera from consecutive patients affected by SpA undergoing cytokine-targeted therapy, HCW and healthy controls from 2015 were analysed through chemiluminescent analytical system for the presence of IgG and IgM anti-SARS-CoV-2. Positive patients (IgM or IgG, or both) additionally underwent real-time Polymerase-Chain-Reaction (RT-PCR) to test for active infection. Serology was repeated at 3-months in SpA. Data across 3 groups were compared by Kruskal Wallis/Chi-square, and between 2 groups by Wilcoxon rank test/Chi-Square. P ≤ 0.05 were considered significant. Results: 200 SpA, 95 HCW and 101 controls were recruited. Positive serology was found in 25(12.5%) SpA, 8(8.4%) HCW, 0(0%) controls (p=0.001). SpA patients with positive serology more frequently reported COVID-19-like symptoms than those with negative serology (20% vs. 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, non severe. No HCW reported symptoms or had positive RT-PCR. In SpA patients, at 3 months, mean IgM titres decreased from 2.76 ± 2.93 to 2.38 ± 2.95 (p=0.001), while IgG titres from 0.89 ± 3.25 to 0.31 ± 0.87 (p=ns). Conclusions: Serology revealed that exposure to SARS-CoV-2 in SpA patients and HCW was higher than expected based on reported symptoms. In SpA, anti-cytokine therapy could act as a protective factor for a severe disease course. However, a seroconversion was not observed at 3-months.

Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFα, anti-IL12/23, or anti-IL17 drugs: a 15-year monocentric real-life study.

OBJECTIVES: We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA). MATERIALS AND METHODS: We enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004-2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan-Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded. RESULTS: Two hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50-3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07-3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22-0.73). CONCLUSIONS: Survival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI. Key Points • Drug survival in PsA patients was confirmed be greater for the first bDMARD administered. • In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches. • Female sex may constitute a predisposing risk factor for flare and therapeutic switches. • Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.

Mediterranean diet in axial spondyloarthritis: an observational study in an Italian monocentric cohort.

BACKGROUND: Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA. METHODS: We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score). RESULTS: A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p = 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36-15.1, p = 0.014), age (per 10-year increase OR 1.05, 1.02-1.68, p = 0.007), and BMI (OR 0.77, 0.63-0.9, p = 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p = 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8-25.3, p = 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement. CONCLUSIONS: Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are less prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement. STUDY REGISTRATION: Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

Beta-catenin interacts with low-molecular-weight protein tyrosine phosphatase leading to cadherin-mediated cell-cell adhesion increase.

Beta-catenin plays a dual role as a major constituent of cadherin-based adherens junctions and also as a transcriptional coactivator. In normal ephitelial cells, at adherens junction level, beta-catenin links cadherins to the actin cytoskeleton. The structure of adherens junctions is dynamically regulated by tyrosine phosphorylation. In particular, cell-cell adhesion can be negatively regulated through the tyrosine phosphorylation of beta-catenin. Furthermore, the loss of beta-catenin-cadherin association has been correlated with the transition from a benign tumor to an invasive, metastatic cancer. Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is a ubiquitous PTP implicated in the regulation of mitosis and cytoskeleton rearrangement. Here we demonstrate that the amount of free cytoplasmic beta-catenin is decreased in NIH3T3, which overexpresses active LMW-PTP, and this results in a stronger association between cadherin complexes and the actin-based cytoskeleton with respect to control cells. Confocal microscopy analysis shows that beta-catenin colocalizes with LMW-PTP at the plasma membrane. Furthermore, we provide evidence that beta-catenin is able to associate with LMW-PTP both in vitro and in vivo. Moreover, overexpression of active LMW-PTP strongly potentiates cadherin-mediated cell-cell adhesion, whereas a dominant-negative form of LMW-PTP induces the opposite phenotype, both in NIH3T3 and in MCF-7 carcinoma cells. On the basis of these results, we propose that the stability of cell-cell contacts at the adherens junction level is positively influenced by LMW-PTP expression, mainly because of the beta-catenin and LMW-PTP interaction at the plasma membrane level with consequent dephosphorylation.

Redox Regulation of Nonmuscle Myosin Heavy Chain during Integrin Engagement.

On the basis of our findings reporting that cell adhesion induces the generation of reactive oxygen species (ROS) after integrin engagement, we were interested in identifying redox-regulated proteins during this process. Mass spectrometry analysis led us to identify nonmuscle myosin heavy chain (nmMHC) as a target of ROS. Our results show that, while nmMHC is reduced in detached/rounded cells, it turns towards an oxidized state in adherent/spread cells due to the integrin-engaged ROS machinery. The functional role of nmMHC redox regulation is suggested by the redox sensitivity of its association with actin, suggesting a role of nmMHC oxidation in cytoskeleton movement. Analysis of muscle MHC (mMHC) redox state during muscle differentiation, a process linked to a great and stable decrease of ROS content, shows that the protein does not undergo a redox control. Hence, we propose that the redox regulation of MHC in nonprofessional muscle cells is mandatory for actin binding during dynamic cytoskeleton rearrangement, but it is dispensable for static and highly organized cytoskeletal contractile architecture in differentiating myotubes.