Real-world treatment patterns in patients with systemic lupus erythematosus: associations with comorbidities and damage.

OBJECTIVE: To assess treatment patterns and the association between long-term glucocorticoid (GC) and hydroxychloroquine (HCQ) use and damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective study including patients with SLE using the computerised database of a large health maintenance organisation. Patients were matched with subjects from the general population. Multivariable logistic regression models were used to assess the association between GC cumulative daily doses, HCQ and comorbidities: Osteoporosis, cardiovascular disease (CVD), hypertension and diabetes mellitus. Models were adjusted for age, sex, socioeconomic status, smoking, disease duration and HCQ use. RESULTS: A total of 1073 patients with SLE were included, 87.79% were women. The age at first diagnosis was 37.23±14.36 and the SLE disease duration was 12.89±6.23 years. Initiation of HCQ within 12 months of SLE diagnosis increased from 51.02% in 2000 to 83.67% in 2010 and 93.02% in 2018. The annual usage of GC gradually decreased from 45.34% in 2000 to 30.76% in 2020. CVD and osteoporosis were more prevalent in SLE than in the general population. Multivariable logistic regression models revealed increased odds for comorbidities in patients receiving a mean daily dose of prednisone of more than 5 mg/day compared with those receiving 5 mg/day or less. CONCLUSIONS: CVD and osteoporosis were more prevalent in SLE than in the general population. The dose and frequency of GC treatment in patients with SLE have decreased over the years. Prednisone usage in doses exceeding 5 mg/day is associated with significantly increased odds of osteoporosis and CVD.

Cardiac Sarcoma Mimicking Libman-Sacks Endocarditis in a Patient with Systemic Lupus Erythematosus (SLE): A Case Report and Literature Review.

We present the case of a 39-year-old woman who was diagnosed with SLE and antiphospholipid antibodies 8 years ago. The chief manifestations of her disease included low-grade fever and polyarthritis. Eight months before presentation, she experienced symptoms attributed to a flare of SLE, leading to an increase in immunomodulatory treatment with no improvement. She presented to the emergency room with acute onset of dyspnea. Clubbing of her fingers and toes was noted. When questioned, she reported the onset of clubbing 5 months earlier. A CTA was performed to rule out pulmonary embolism, which was excluded, although it revealed a severely damaged mitral valve with severe insufficiency and a large mass on the valve, protruding into the left atrium. Antibiotics were started, with a working diagnosis of infectious endocarditis; however, the severe mitral valve dysfunction lead to emergency mitral valve replacement, revealing an organized thrombus. She was treated with anticoagulation, with a working diagnosis of Libman-Sacks endocarditis, with no improvement. Additional immunosuppression failed to improve her symptoms. Enlargement of the thrombotic mass and an increased gradient across the prosthetic mitral valve led to repeat surgery, culminating in a diagnosis of high-grade sarcoma within the left atrial mass. We further discuss cardiac sarcoma and describe the occurrence of clubbing in patients with sarcoma. This case highlights the importance of interdisciplinary collaboration and the need for vigilant monitoring in refractory cases, particularly when atypical presentations arise.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

OBJECTIVE: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. METHODS: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. RESULTS: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. CONCLUSION: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

OBJECTIVES: To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. METHODS: Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. RESULTS: A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. CONCLUSIONS: Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

Heart Valve Surgery in Antiphospholipid Syndrome Patients-Morbidity and Mortality.

OBJECTIVES: To assess valve surgery outcomes in antiphospholipid syndrome (APS). METHODS: A retrospective study assessing complications and mortality rate and possible factors associated with adverse outcomes of APS patients undergoing valve surgery in two tertiary medical centers. RESULTS: Twenty-six APS patients (median age at surgery 47.5 years) who underwent valve surgery were detected, of whom 11 (42.3%) had secondary APS. The mitral valve was most commonly involved (n = 15, 57.7%). A valve replacement was performed in 24 operations (92.3%), 16 of which (66.7%) were mechanical valves. Fourteen (53.8%) patients sustained severe complications, and four of them died. The presence of mitral regurgitation (MR) was associated with severe complications and mortality (odds ratio (95% confidence interval) 12.5 (1.85-84.442), p = 0.008, for complications. All deceased patients had MR (p = 0.033). The presence of Libman-Sacks endocarditis (LSE) (7.333 (1.272-42.294), p = 0.045), low C3 (6.667 (1.047-42.431), p = 0.05) and higher perioperative prednisone doses (15 ± 21.89 vs. 1.36 ± 3.23 mg/day, p = 0.046) were also associated with complications. A lower glomerular filtration rate (GFR) was associated with mortality (30.75 ± 19.47 vs. 70.68 ± 34.44 mL/min, p = 0.038). CONCLUSIONS: Significant morbidity and mortality were observed among APS patients undergoing valve surgery. MR was associated with mortality and complications. LSE, low complement and higher doses of corticosteroids were associated with complications, while a low GFR was associated with mortality.

Synovial monocytes from psoriatic and rheumatoid arthritis patients are modulated differently by TNF inhibitors and glucocorticoids: an ex-vivo study.

OBJECTIVES: Synovial monocytes (expressing CD14+CD16+) affect pro-inflammatory responses in the synovium microenvironment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). The effect of various drugs on those cells was evaluated. METHODS: Synovial fluid mononuclear cells (SFMCs) from PsA (n=29) and RA (n=11) patients were cultured with biologics or glucocorticoids (GCs). CD14+CD16+ cells were analysed by flow cytometry. TNF secretion was assessed by ELISA and changes in cytokine and matrix metalloproteinase-9 (MMP-9) mRNA by qPCR. RESULTS: TNF inhibitors (i) [adalimumab (ADA) and infliximab (IFX)] significantly reduced the %CD14+CD16+ cells (p<0.04 and p<0.02, respectively) compared to IL-17Ai, IL-12/23i, and GCs in PsA patients' SFMCs. Similarly, those TNFi reduced the %CD14+CD16+ cells (p<0.05 and p<0.02, respectively) compared to IL-6Ri, CD20i and GCs in RA patients' SFMCs. TNFi (ADA p<0.01, IFX p=0.0003), and GCs (p<0.05) reduced TNF levels in PsA patients SFMCs supernatants. IFX down-regulated IL-1ß mRNA (p<0.005) while GCs betamethasone (BET) (p<0.01) and methylprednisolone acetate (MPA) (p<0.005) led to IL-1ß up-regulation. IFX down-regulated IL-8 and MMP-9 (p<0.01) and up-regulated IL-10 (p<0.005), and GCs did so to a greater extent (for IL-8, BET p<0.0001 and MPA p<0.005, for MMP-9, BET and MPA p<0.0001 and for IL-10, BET and MPA p<0.0001). CONCLUSIONS: TNFi but not GCs reduced the inflammatory monocytes. Both TNFi and GCs inhibited TNF secretion but differently modulated IL-1ß, IL-8, MMP-9 and IL-10 gene expression. Our data point to TNFi as a modulator of synovial monocytes.

Systemic Lupus Erythematous and Obstructive Sleep Apnea: A Possible Association.

Marked fatigue is common in patients with systemic lupus erythematosus (SLE). This study aimed to assess the association of sleep disorders, including obstructive sleep apnea (OSA), with SLE. Forty-two consecutive patients with SLE and 20 healthy controls were recruited and underwent a one-night ambulatory sleep examination. They completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and Functional Assessment of Chronic Illness Therapy (FACIT). SLE disease activity and damage were assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). A significantly increased apnea/hypopnea index was noted in the SLE group compared to healthy controls (p = 0.004). SLE patients had higher rates of moderate-to-severe OSA (p = 0.04), PSQI (p = 0.001), and FACIT scores (p = 0.0008). Multivariate analysis revealed that the SDI was associated with OSA (p = 0.03). There was a positive association between SLEDAI-2K and moderate-to-severe OSA (p = 0.03). Patients with SLE had an increased prevalence of OSA and poorer quality of sleep compared to healthy controls. Our findings suggest that active disease and accumulated damage may be associated with OSA. These findings highlight the importance of identifying the presence of OSA in patients with SLE.

A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

Sex-Based Differences in Sonographic and Clinical Findings Among Patients With Psoriatic Arthritis.

OBJECTIVE: To investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA). METHODS: The study population included consecutive prospectively recruited patients with PsA, as determined by the CASPAR (Classification for Psoriatic Arthritis) criteria, who underwent clinical and physical examinations, followed by a detailed ultrasound (US) evaluation (greyscale and Doppler). US evaluation included 52 joints, 40 tendons, and 14 points of entheses (Modified Madrid Sonographic Enthesis Index [MASEI] plus lateral epicondyles) performed by an experienced sonographer blinded to the clinical data. The US score was based on the summation of a semiquantitative score for synovitis, tenosynovitis, and enthesitis. The US enthesitis score was categorized into inflammatory lesions (ie, hypoechogenicity, thickening, bursitis, and Doppler) and structural lesions (ie, enthesophytes/calcifications and erosions). RESULTS: The study population of 158 patients included 70 males and 88 females. The males had higher rates of employment (P = 0.01), Psoriasis Area and Severity Index scores (P = 0.04), and mean swollen joint counts (P = 0.04). The total US score and its subcategory scores-the synovitis and tenosynovitis scores-were similar for both sexes, whereas the total enthesitis score and its subcategory score-the inflammatory enthesitis score-were significantly higher for the males compared to the females (P = 0.01 and P = 0.005, respectively). Hypoechogenicity, thickening, and enthesophytes were more prevalent in males compared to females (P < 0.05). Multivariate ordinal logistic regression models showed that male sex was associated with a higher US inflammatory enthesitis score compared to female sex (odds ratio 1.96, P = 0.02). CONCLUSION: Sonographic enthesitis was more prevalent in males compared to females with PsA. These differences were not reflected by enthesitis disease activity scores derived from clinical assessment.

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study.

OBJECTIVES: To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls. METHODS: A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2-6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample. RESULTS: The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1. CONCLUSIONS: The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.