B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single-arm cohort study of telitacicept.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI-4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti-dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow-up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT-Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B-cell lymphoma were occurred. In our first prospective real-world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed.

Association between triglyceride-glucose index and carotid atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To investigate the association of the triglyceride-glucose (TyG) index with atherosclerotic risk among patients with PsA. METHODS: This cross-sectional study included 165 consecutive PsA patients receiving carotid ultrasonography with integrated TyG index, calculated as ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Logistic regression models were applied to analyse the association of TyG index as continuous variables and tertiles with carotid atherosclerosis and carotid artery plaque. Fully adjusted model included sex, age, smoking, BMI, comorbidities and psoriatic-related variables. RESULTS: Overall, PsA patients with carotid atherosclerosis had substantially higher TyG index than those without [8.82 (0.50) vs 8.54 (0.55), P = 0.002]. The frequency of carotid atherosclerosis was increased with increases in TyG index tertiles, showing 14.8%, 34.5%, 44.6% for tertile 1, 2 and 3, respectively (P = 0.003). Multivariate logistic analyses showed that each 1-unit increase in TyG index was significantly associated with prevalent carotid atherosclerosis [unadjusted odds ratio (OR) 2.65 (1.39-5.05); fully adjusted OR 2.69 (1.02-7.11)]. Compared with patients in tertile 1 of TyG index, the unadjusted and fully adjusted OR for occurrence of carotid atherosclerosis were 4.64 (1.85-11.60) and 5.10 (1.54-16.93) in patients in tertile 3. Similarly, higher prevalent carotid artery plaque was observed with increasing TyG index [unadjusted OR 3.11 (1.54-6.26); fully adjusted OR 3.61 (1.15-11.38)] or in tertile 3 vs tertile 1 [unadjusted OR 10.20 (2.83-36.82); fully adjusted OR 17.89 (2.88-111.11)]. Additionally, TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in discrimination ability (all P < 0.001). CONCLUSIONS: TyG index was positively correlated with the burden of atherosclerosis in PsA patients, independent of traditional cardiovascular risk factors and psoriatic-related factors. These findings suggest that TyG index may be a promising atherosclerotic marker for the PsA population.

Discrepancy in Metabolic Syndrome between Psoriatic Arthritis and Rheumatoid Arthritis: a Direct Comparison of Two Cohorts in One Center.

OBJECTIVE: We aimed to investigate the discrepancy in metabolic syndrome (MS) and cardiovascular disease (CVD) between patients with psoriatic arthritis (PsA) and those with rheumatoid arthritis (RA). METHODS: Patients with PsA and RA were enrolled between 1 December 2018 and 31 December 2021. Data on their demographics, height, weight, waist circumference, clinical and laboratory data, and comorbidities were collected. Disease activities of patients with RA and PsA were assessed. Prevalence was estimated by dividing cases (such as MS and CVD) of PsA and RA individually. Propensity score matching and inverse probability of treatment weighting were used for further validation. RESULTS: Consecutively, 197 patients with PsA and 279 patients with RA were enrolled in this study. Both MS [36.0% versus 23.3%, p = 0.002, OR 1.54 (1.16, 2.05)] and CVD [6.6% versus 1.1%, p = 0.001, OR 6.13 (1.77, 21.25)] were more frequently observed in patients with PsA compared with patients with RA. The frequency of abdominal obesity was also higher in patients with PsA [61.9% versus 33.0%, OR 1.87 (1.53, 2.29), p < 0.001]. After 1:1 propensity score matching for age, sex, smoking history, serum lipids, and disease activity, MS remained more common in 117 patients with PsA than in 117 patients with RA (37.6% versus 23.1%, p = 0.016) These findings remained after the inverse probability of treatment weighting in 196 patients with PsA and 288 patients with RA. A positive linear relationship between MS with disease activity was found in patients with PsA, but not in patients with RA. CONCLUSION: Considerable discrepancies in MS and CVD were observed between patients with PsA and those with RA. The greater odds of MS and CVD emphasize the need to pay more attention to metabolic and cardiovascular conditions in patients with PsA.

Improved diagnostic performance of CASPAR criteria with integration of ultrasound.

Background: The difficulty in determining synovitis, tenosynovitis, or enthesitis by physical examination (PE) has limited the diagnostic capability of CASPAR for psoriatic arthritis (PsA). Therefore, we aimed to evaluate the diagnostic utility of CASPAR with the integration of ultrasound (US). Methods: Patients with a hint of PsA were enrolled. Besides routine PE for tender or swollen joints, enthesitis, and dactylitis, US was performed to evaluate peripheral joints, entheses, and tendons. The additional value of the US to the CASPAR criteria was analyzed. Results: A total of 326 consecutive patients with 164 PsA and 162 non-PsA were enrolled. A total of 162 non-PsA patients consisted of 58 cases of psoriasis (PsO), 27 osteoarthritis with PsO/family history of PsO, five fibromyalgia with PsO, 69 sero-negative rheumatoid arthritis, and three undifferentiated arthritis. Significantly higher frequencies of tenosynovitis and enthesitis on US and new bone formation on X-rays were found in PsA vs. non-PsA patients (59.1% vs. 13.0%; 63.4% vs. 14.2%; 62.2% vs. 8.0%, p <0.01 for all). Logistic regression analysis showed that dactylitis (OR = 12.0, p <0.01), family history of PsO/PsA (OR = 3.1, p <0.05), nail involvement (OR = 3.5, p = 0.01), new bone formation on X-ray (OR = 14.8, p <0.01), tenosynovitis on US (OR = 21.3, p <0.01), and enthesitis on US (OR = 21.7, p <0.01) were independent risk factors for PsA. By combining US tenosynovitis and/or enthesitis, the diagnostic utility of CASPAR criteria was improved, with superior specificity (91.4% vs. 84.0%) and similar sensitivity (95.7% vs. 94.5%). Replacing X-ray by US or adding US, the CASPAR criteria showed comparable sensitivity and specificity for PsA diagnosis. The diagnostic accuracy was 89.3% for CASPAR criteria based on PE, 93.6% for CASPAR added with US, and 93.3% for CASPAR with US replacing X-ray. Conclusion: The diagnostic utility of the CASPAR was improved by integrating tenosynovitis and/or enthesitis when using US. US provides additional value for PsA recognition.

Risk factors associated with osteoporosis and fracture in psoriatic arthritis.

BACKGROUND: Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA. METHODS: A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed. RESULTS: Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ±â€Š0.193 vs. 0.901 ±â€Š0.152 g/cm2, P  = 0.041; 0.780 ±â€Š0.146 vs. 0.865 ±â€Š0.166 g/cm2, P  = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = -0.503, -0.580, -0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = -0.521, -0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026-1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214-1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002-1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012-44.180, P < 0.05) were risk factors for fracture in the multivariate model. CONCLUSIONS: Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.

Clinical Characteristics of Psoriatic Arthritis in Chinese Patients: A Cross-Sectional Study.

INTRODUCTION: The clinical features of psoriatic arthritis (PsA) varied in different studies from different countries, nevertheless rarely reported from China. We aimed to show the portraits of Chinese PsA patients. METHODS: Demographics as well as clinical and laboratory data at the first visit of a PsA cohort were collected. Joints and entheses were further assessed by imaging techniques. The correlation between psoriasis severity index (PASI) and disease activity in PsA (DAPSA) was analyzed. The metabolic comorbidities were also explored among patients with different disease activity. RESULTS: Three hundred patients with definite PsA were enrolled in this study; 159 (53.0%) of them were male. Their median age was 39 (31, 51) years with disease duration of 3 (0.6, 7) years; 15.6% patients were HLA-B27-positive, and 37.8% patients reported a family history of psoriasis or PsA. Among 300 patients, psoriasis presented earlier than arthritis in most of them (214, 74.0%), while 48 (16.6%) patients presented with arthritis before psoriasis. Articular involvement was found in 293 (97.7%) patients. Polyarticular type was most common, with proximal interphalangeal as most frequently involved joints. Axial joint involvement was found in 45 (15.4%) patients. Dactylitis was observed in 94 (31.3%) patients, most often at the second, third, and fourth toes. Enthesitis was found in 18 (6.0%) patients by physical examination, however in 129/227 (56.8%) patients by ultrasound. The DAPSA score was correlated with PASI (r = 0.22, p = 0.021). A variety of comorbidities were more often observed in patients with moderate/high disease activity comparing with those in remission/low-disease activity, especially type 2 diabetes with statistically significant difference (19.1 vs. 4.1%, p = 0.023). However, further logistic regression analysis showed diabetes was not independently associated with moderate/high disease activity. The most frequently prescribed medication was methotrexate (101, 66.4%). Biological agents were applied in 25 (16.4%) patients. CONCLUSIONS: Polyarticular involvement was most common in Chinese PsA patients. Ultrasound dramatically increased the identification of peripheral enthesitis. Active PsA patients were more likely to have comorbidities.

Modifiable lifestyle and environmental factors associated with onset of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational studies.

BACKGROUND: Psoriatic arthritis (PsA) is a progressive joint disease associated with psoriasis. OBJECTIVES: To investigate the association of modifiable lifestyle and environmental factors with PsA risk among people with psoriasis. METHODS: We conducted a systematic search of PubMed, Embase, and Cochrane Library through May 2, 2020, for observational studies reporting lifestyle or environmental factors for PsA onset in patients with psoriasis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random-effects model. RESULTS: We included 16 studies comprising 322,967 individuals. Obesity and being overweight were associated with an increased PsA risk in patients with psoriasis (OR, 1.75 [95% CI, 1.42-2.16] and OR, 1.50 [95% CI, 1.08-2.09], respectively), with an increase of approximately 6% for each kg/m2 rise in body mass index (OR, 1.06; 95% CI, 1.03-1.10). The presence of PsA was associated with a history of physical trauma (OR, 1.33; 95% CI, 1.16-1.54) or fracture (OR, 1.46; 95% CI, 1.22-1.74). No significant associations were observed regarding alcohol consumption (OR, 0.99; 95% CI, 0.88-1.13), smoking (OR, 0.89; 95% CI, 0.75-1.06), female hormonal exposure (OR, 1.45; 95% CI, 0.95-2.20), and psychologically traumatic events. LIMITATIONS: Inherent limitations in the included observational studies. CONCLUSIONS: Several lifestyle and environmental factors are associated with PsA onset among patients with psoriasis. These findings indicate that such risk may be modified with lifestyle changes or avoidance of physical trauma in people with psoriasis.

Immune checkpoint inhibitors therapies in patients with cancer and preexisting autoimmune diseases: A meta-analysis of observational studies.

INTRODUCTION: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge. OBJECTIVE: To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy. METHODS: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD. RESULTS: 619 ICI-treated patients with PAD in 14 publications were finally identified. In the random-effects meta-analysis, pooled incidence of PAD flares, de novo immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). Separately, there were 219 and 206 patients experiencing PAD exacerbation and de novo irAEs of any grade, yielding a pooled incidence of 35% (95%CI = 29%-41%) and 33% (95%CI = 24%-42%) respectively. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95%CI = 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR = 1.08, 95%CI = 0.72-1.62), but a trend toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33). CONCLUSIONS: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.

Salivary gland ultrasound integrated with 2016 ACR/EULAR classification criteria improves the diagnosis of primary Sjögren's syndrome.

OBJECTIVES: To evaluate the utility of salivary gland ultrasound (SGUS) in the diagnosis of primary Sjögren's syndrome (pSS) singly or integrated with 2016 ACR/EULAR classification criteria. METHODS: Patients with suspected pSS were enrolled in the study. SGUS semi-quantitative scoring was used to assess salivary gland. Clinical characteristics were recorded, including autoantibodies, ophthalmic tests, salivary glands scintigraphy (SGS) and labial biopsy. The diagnostic accuracy of SGUS score and complementary value of SGUS to 2016 ACR/EULAR criteria were analysed. RESULTS: 282 patients were included for analysis. 161 were diagnosed as pSS and 121 as non-SS. SGUS score≥5 showed 64.7% sensitivity and 81.4% specificity for the diagnosis of pSS. Positive anti-SSA, abnormal SGS and SGUS score were significantly higher in pSS than non-SS group (80.1% vs. 14.0%, p<0.01; 91.3% vs. 57.0%, p<0.01; 8.4±6.6 vs. 2.6±3.2, p<0.01 respectively). A weighted score [(anti-SSA×16.5) + (SGS×14.5) + (SGUS×4.5)] was constructed. The score ≥17.5 could improve the sensitivity, and almost keep the specificity comparing to 2016 ACR/EULAR criteria (89.9% vs. 85.6% and 79.5% vs. 82.2%). When replacing labial biopsy by SGUS in 2016 ACR/EULAR criteria, both sensitivity and specificity were a bit decreased (85.0% vs. 85.6% and 79.8% vs. 82.2%). When adding SGUS to 2016 ACR/EULAR criteria, it showed better performance by improving the sensitivity (90.8% vs. 85.6%), while not losing the specificity (83.7% vs. 82.2%). CONCLUSIONS: Adding SGUS score to the 2016 ACR/EULAR criteria can improve the diagnosis utility of pSS. SGUS may be a feasible and prospective tool in the diagnosis of pSS.

[Effect of graft-versus-host disease on relapse and survival in 100 patients after allogeneic hematopoietic stem cell transplantation].

The study was aimed to investigate the incidences and risk factors of acute and chronic graft-versus-host diseases (GVHD) and to clarify their effects on relapse and survival of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 100 cases of allo-HSCT were retrospectively analyzed. The incidences and risk factors of aGVHD and cGVHD, relapse and survival were studied. The results showed that 31 cases developed aGVHD of II - IV grade (34.4%) and 14 cases developed aGVHD of III - IV grade (17.7%). HLA matched or mismatched did not show significant difference in the development of aGVHD of II - IV grade (p > 0.05). Previous occurrence of aGVHD was the risk factor for cGVHD (HR = 2.303, p = 0.088). The female was a favorable factor for cGVHD (HR = 0.401, p = 0.055). The relapse rate was lower in patients who developed cGVHD. The development of aGVHD of II - IV grade was the risk factor for overall survival (p < 0.05). The mortality of patients with aGVHD of III - IV grade and mortality of patients with aGVHD of 0 - I grade were 81.0% and 35.7% respectively, there was very significant difference between them (p = 0.000). In conclusion, till now GVHD and graft-versus-leukemia (GVL) effect can not be separated. The positive effect of GVL could be counteracted by GVHD-related mortality. It is necessary to prevent and control the development of severe aGVHD. The development of local cGVHD may be beneficial to the long-term disease-free survival of patients after allo-HSCT.