Comparison of the Effectiveness and Safety of Mycophenolate Mofetil and Cyclophosphamide in Lupus Nephritis: Evidence from a Real-World Study.

INTRODUCTION: Both mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) have been recommended in the induction therapy of lupus nephritis (LN) for years; nevertheless, their effectiveness and safety in a real-world setting are extremely lacking. Therefore, we decided to conduct this real-world study. METHODS: A total of 195 Chinese patients with LN who were initially treated with MMF (n = 98), or intravenous CYC (n = 97) as induction therapy were enrolled. All of the patients were followed up to 12 months. Complete renal remission (CRR) was defined as 24-h urinary protein (24 h-UTP) < 0.5 g, and partial renal remission (PRR) was defined as ≥ 50% reduction in 24 h-UTP to the subnephrotic level, however > 0.5 g, both with a change of serum creatinine (SCr) within 10% from baseline. The proportions of CRR, PRR, and total renal remission (TRR), as well as adverse events, were compared by Chi-square test and Kaplan-Meier analysis (log-rank test). Inverse probability of treatment weighting (IPTW) was used for propensity score matching and multivariable logistic regression analyses were employed. RESULTS: The cumulative proportion of TRR in 6 months (79.4 vs. 63.8%, p = 0.026) and CRR in 12 months (72.8 vs. 57.6%, p = 0.049) in MMF group were significantly higher than CYC group, and the above conclusions were further confirmed by IPTW. The proportions of PRR, CRR, and TRR at other time points were equivalent between two groups. Further subgroup analysis in 111 patients with biopsy-proven III-V LN also showed a significantly higher proportion of TRR at 6 months in the MMF group than in the CYC group (78.3 vs. 56.9%, p = 0.026). In the Kaplan-Meier analysis and after IPTW, the MMF group showed better TRR and CRR responses than CYC group in 12 months. Multivariable logistic regression analyses revealed that MMF use was the only predictor of CRR (HR 2.12, 95% CI 1.90-4.09, p = 0.026), while low complement level was also a predictor, albeit risk was reduced (HR 0.38, 95% CI 0.17-0.86, p = 0.019). Moreover, compared to the CYC group, MMF group patients were more likely to have significantly lower SCr (µmol/l) [72.5 (62.5, 86.5) vs. 79.0 (71.1, 97.5), p = 0.001] and daily dose of prednisone (mg/day) (15.7 ± 5.2 vs. 18.6 ± 11.3, p = 0.022) at 6 months; lower 24 h-UTP (g) [0.1 (0.1, 0.3) vs. 0.2 (0.1, 0.9), p = 0.005] and daily dose of prednisone (mg/day) (9.6 ± 3.3 vs. 11.2 ± 5.5, p = 0.023) at 12 months. Infection was the most common adverse event. Pneumonia and gastrointestinal discomfort were more frequently observed in the CYC group. CONCLUSIONS: Real-world data are a key component of the evidence supporting the effectiveness of drugs and are of interest to all stakeholders. Our comparative study demonstrated the effectiveness of MMF in LN induction therapy was at least equivalent to intravenous CYC, with superior tolerance.

Clinical value of plasmablasts in predicting disease relapse in patients with IgG4-related disease.

OBJECTIVES: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD). METHODS: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated. RESULTS: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/µL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012). CONCLUSIONS: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points • The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. • The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. • The application of LEF is an independent protective factor for disease relapse in IgG4-RD.

Impact of Treat-to-Target Therapy on Bone Mineral Density Loss in Patients With Rheumatoid Arthritis: A Prospective Cohort Study.

Background: Osteoporosis is a common comorbidity of rheumatoid arthritis (RA). Although RA disease activity has been demonstrated to be associated with bone loss in previous studies, most of them were cross-sectional studies and not in the context of treat-to-target (T2T) strategies. Objectives: This study aimed to evaluate the association of disease activity with bone mineral density (BMD) changes in the context of T2T strategies in a prospective RA cohort. Methods: RA patients were enrolled from a prospective CENTRA cohort of Peking University First Hospital. The follow-ups have been scheduled every 3 to 6 months. BMD was repeated at baseline, 1 year, and then every other year. Demographics, baseline clinical features, laboratory data, and medications at each visit were recorded. Time-adjusted mean disease activity scores were adopted to reflect the overall disease activity during follow-up. The influence of univariable associations between predictors and BMD was investigated using linear regression. Results: A total of 268 patients were included in our analysis. Their mean age was 50 (12.9) years, and 224 (83.6%) were women. The median (IQR) disease duration was 48.7 (107.6) months. Osteoporosis in the lumbar spine was observed in 23.1% of patients and 9.3% in the femoral neck at enrollment. Older age, higher SDAI score, and lower BMI were associated with osteoporosis at baseline. The proportion of patients who achieved DAS28-ESR, CDAI, and SDAI remission or LDA at the end of the first year was 71.5%, 68.8%, and 67.4%, respectively. Reevaluations of BMD at 1 year were applied to 144 patients. Mean decreases of BMDs were 1.75% at the lumbar spine and 1.40% at the femoral neck at 1 year from baseline, respectively. Patients who achieved remission had less yearly bone loss in the lumbar spine (p = 0.036). Female gender was identified as a risk factor in the multiple linear regression analyses, and lower disease activity and bisphosphonates were protective factors of continuous bone loss. Conclusion: Disease activity is associated with bone loss in RA patients in the context of T2T strategies, and those who achieved remission had less yearly bone loss.

Low-dose glucocorticoids withdrawn in systemic lupus erythematosus: a desirable and attainable goal.

OBJECTIVES: To assess the risk of flare in systemic lupus erythematosus (SLE) patients after low-dose glucocorticoid (GC) discontinuation and to evaluate the risk factors of flare. METHODS: SLE patients who ever discontinued GCs were identified from the Peking University First Hospital SLE cohort. The disease flare profile after GC discontinuation was analysed. The flare rate was analysed using Kaplan-Meier analysis. Cox regression was used to determine the effects of variables on SLE flare. A prognostic nomogram using Cox proportional hazards regression modelling was developed. RESULTS: A total of 132 SLE patients were eligible for the final analysis. They were followed up for a median of 21.8 months (interquartile range 9.01-36.7). The cumulative probability of flare after GC discontinuation was 8.3% at 6 months, 16.8% at 1 years and 27.5% at 2 years. In multivariate Cox analysis, hypocomplementemia and serologically active clinically quiescent (SACQ) were independent risk factors of flare [hazard ratio (HR0 2.53 (95% CI 1.32, 4.88); HR 3.17 (95% CI 1.44, 6.97), respectively]. Age ≥40 years at GC withdrawal and hydroxychloroquine (HCQ) usage were independent protective factors of flare [HR 0.53 (95% CI 0.29, 0.99); HR 0.32 (95% CI 0.17, 0.62), respectively]. The protective effect of HCQ was dosage related. From the perspective of different tapering strategies embodied as the duration from prednisone 5 mg/day to complete discontinuation, a slower tapering strategy (12-24 months) significantly reduced the risk of flare compared with a faster tapering strategy (<3 months) [HR 0.30 (95% CI 0.11, 0.82), P = 0.019]. The prognostic nomogram including the aforementioned factors effectively predicted the 1 and 2 year probability of being flare-free. CONCLUSION: Low-dose GC is feasibly discontinued in real-life settings. SACQ and younger age are potential risk factors of SLE flare, while HCQ use and slow GC tapering to withdrawal can reduce relapse. The visualized model we developed may help to predict the risk of flare among SLE patients who discontinued GC.

Flare rates and factors determining flare occurrence in patients with systemic lupus erythematosus who achieved low disease activity or remission: results from a prospective cohort study.

OBJECTIVE: To investigate the frequency and determinants of flare in Chinese patients with lupus, focusing on the effect of glucocorticoid (GC) tapering on flare in patients who achieved low disease activity or remission. METHODS: We collected baseline and follow-up data from all consecutive patients in a prospective lupus cohort between January 2017 and December 2020. We defined low disease activity using the lupus low disease activity status (LLDAS), applied the DORIS (Definitions of Remission in SLE) for remission criteria and then assessed flare using the SELENA-SLEDAI Flare Index. RESULTS: Among a total of 185 patients enrolled, 139 exhibited low disease activity or remission with a median follow-up of 29.8 (21.2-35.2) months. The flare rates after achievement of LLDAS, clinical remission and complete remission on treatment were 0.23, 0.12 and 0.1 per patient-year, respectively. In contrast, the flare rate of patients who never achieved remission or LLDAS was 0.49 per patient-year. In patients with LLDAS or remission achievement, multivariate Cox regression analysis showed that lower C3 level at the time of first achieving LLDAS or clinical remission was an independent predictive factor for subsequent flares. Kaplan-Meier curves showed a significantly lower flare-free survival during the subsequent follow-up in patients with GC withdrawal compared with those maintained on a low dose of prednisone (≤7.5 mg/day) (HR=6.94, 95% CI 1.86 to 25.86, p=0.004). However, no significant differences in flare were observed in patients maintained on different low doses of prednisone (>5 mg/day and ≤7.5 mg/day vs >2.5 mg/day and ≤5 mg/day vs >0 mg/day and ≤2.5 mg/day) (p=0.200). CONCLUSIONS: Target achievement significantly lowered the rate of subsequent flare, from the perspective of both stricter targets and longer period in targets. C3 level was a strong predictor of flare in patients who have achieved treatment targets. Although GC tapering to minimal doses was feasible, its withdrawal may accelerate the risk of recurrence.

Hepatitis B virus in cerebrospinal fluid of a patient with purulent bacterial meningitis detected by multiplex-PCR: A case report.

BACKGROUND: Bacterial meningitis (BM) is a common central nervous system inflammatory disease. BM may cause serious complications, and early diagnosis is essential to improve the prognosis of affected patients. CASE SUMMARY: A 37-year-old man was hospitalized with purulent meningitis because of worsening headache for 12 h, accompanied by vomiting, fever, and rhinorrhea. Head computed tomography showed a lesion in the left frontal lobe. Infectious disease screening showed positivity for hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B core antigen. Cerebrospinal fluid (CSF) leak was suspected based on clinical history. Streptococcus pneumoniae (S. pneumoniae) was detected in CSF by metagenomic next-generation sequencing (mNGS) technology, confirming the diagnosis of purulent BM. After treatment, multiplex PCR indicated the presence of hepatitis B virus (HBV) DNA and absence of S. pneumoniae DNA in CSF samples. CONCLUSION: We report a rare case of HBV in the CSF of a patient with purulent BM. Multiplex PCR is more sensitive than mNGS for detecting HBV DNA.

Telitacicept, a novel humanized, recombinant TACI-Fc fusion protein, for the treatment of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which aberrant immune cells and proinflammatory mediators act as key players in the pathogenesis of the disease. Telitacicept (RC-18) is a novel, recombinant fusion protein, consisting of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and the Fc portion of human immunoglobulin G (IgG) (TACI-Fc). It was designed to inhibit the activity of two target cytokines, the B-cell lymphocyte stimulator (BLyS, also known as the B-cell activation factor [BAFF]) and a proliferation-inducing ligand (APRIL), both of which are involved in B cell-mediated autoimmune diseases. In Chinese patients with moderate to severe SLE, subcutaneous telitacicept (80, 160 and 240 mg) in combination with standard therapy was associated with clinical benefit and appeared to be well tolerated. On March 9, 2021, the Chinese National Medical Products Administration (NMPA) granted telitacicept conditional marketing approval for the treatment of adult patients with active, autoantibody-positive SLE. Additionally, on April 15, 2020, the U.S. Food and Drug Administration (FDA) granted fast track designation to telitacicept for the treatment of SLE. Here, we provide a comprehensive review of the preclinical and clinical activity of telitacicept in SLE.

Determinants and protective associations of the lupus low disease activity state in a prospective Chinese cohort.

OBJECTIVE: To investigate the frequency and determinants of achieving the lupus low disease activity state (LLDAS), and the effect of LLDAS attainment on disease flare and damage accrual in a prospective, single-center cohort of Chinese lupus patients. METHODS: Baseline and follow-up data from consecutive patients at the Peking University First Hospital were collected from January 2017 to June 2020. RESULTS: A total of 185 patients were enrolled, with median (range) disease duration at enrolment of 2.3 (0.8-7.7) years, and median follow-up of 2.2 (1.0-2.9) years. By the end of the study, 139 (75.1%) patients had achieved LLDAS at least once; 82 (44.3%) patients achieved LLDAS for ≥ 50% of observations. Multivariable logistic regression analysis showed that 24-h urinary total protein (UTP; per g) (OR = 0.447, 95%CI [0.207-0.968], p = 0.041), serum creatinine (Scr; per 10 µmol/L) (OR = 0.72, 95%CI [0.52-0.99], p = 0.040), and C3 level (per 100 mg/L) (OR = 1.60, 95%CI [1.18-2.17], p = 0.003) at recruitment had independent negative associations with achieving LLDAS for ≥ 50% of observations. Kaplan-Meier analyses showed a significant reduction in flare rate with increased proportion of time in LLDAS. Attainment of LLDAS in at least 50% of observations was an independent protective factor for damage accrual (OR = 0.19, 95%CI [0.04-0.99], p = 0.049). CONCLUSIONS: In this prospective Chinese cohort, LLDAS was an attainable goal in clinical practice. Nephritis-related markers (UTP and Scr) and C3 level at recruitment negatively influenced achievement of LLDAS. LLDAS achievement was significantly protective from flare and damage accrual. KEY POINTS: • Low disease activity status (LLDAS) is an achievable target during SLE treatment in China. Urine protein, serum creatinine, and C3 level at recruitment independently affect LLDAS achievement in this group of Chinese lupus patients. • As a treatment target, LLDAS achievement has a highly protective effect for preventing flare and damage accrual, especially in case of achieving LLDAS for ≥ 50% of observations. • The present results further highlight the practical significance of treat-to-target principle in SLE management (T2T/SLE) and the needs for promoting the application of T2T/SLE in clinical practice as well as exploring the concrete implement strategy.

Treatments and outcomes in Chinese patients with serologically active clinically quiescent systemic lupus erythematosus: a retrospective observational study.

OBJECTIVE: To clarify the frequency and outcome of patients with systemic lupus erythematosus (SLE) who achieved the clinical state as serologically active clinically quiescent (SACQ) and to identify factors associated with the flare of disease. METHODS: Clinical data of patients diagnosed as SLE and followed in Peking University First Hospital from 2009 to 2015 were retrospectively reviewed. Six hundred eighty-two patients who were followed up for more than 6 months were analyzed. SACQ was defined as an at least a 6-month period with persistent serologic activity and without clinical activity and daily dose of prednisone or equivalent were less than 7.5 mg. Serologically quiescent clinically quiescent (SQCQ) patients served as control groups. Data including demographics, initial symptoms, duration to SACQ, treatments before and after SACQ, and characteristics of the patients suffered from flare were analyzed. RESULTS: Among the 682 patients, 170 patients were SACQ (24.9%) and 187 patients were SQCQ. SQCQ patients (38.61 ± 15.08 years old) were older at baseline than SACQ patients (38.61 ± 15.08 years vs. 32.09 ± 14.35 years, p < 0.001). Of 170 SACQ patients, 32.9% experienced flare that was significantly higher than 15.5% of SQCQ patients (29/187). Corticosteroids (OR 1.323, 95% CI 1.129 to 1.550; p = 0.001) was an independent risk factor for flare, while antimalarials (OR 0.045, 95% CI 0.004 to 0.474; p = 0.010) and immunosuppressants (OR 0.332, 95% CI 0.156 to 0.706; p = 0.004) were protective factors in SACQ patients; however, only antimalarials was protective factors in SQCQ patients (OR 0.028, 95% CI 0.001 to 0.743; p = 0.033). CONCLUSION: About one third of SLE patients with SACQ experience flare, significantly more frequent than that of patients with SQCQ. Thus, approach to prevent flare in SACQ patient is required. Maintenance therapy of hydroxychloroquine and immunosuppressant agents may be protective and beneficial treatment strategy in these patients.

Predicting lupus low disease activity state and remission in SLE: novel insights.

Introduction:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with extreme heterogeneity, which sometimes may be life-threatening. Principles of treat to target (T2T) in SLE were put forward more recently, leading to better long-term survival and reduced damage accrual.Areas covered: Lupus low disease activity state (LLDAS) and remission are currently the most widely accepted principal goals of SLE-T2T recommendations. In this article, we will deliver the novel insights into the definitions of LLDAS/remission, attainability, and, most importantly, clinical predictors of LLDAS and remission in SLE.Expert opinion: Since the release of the LLDAS and the framework on definitions of remission in SLE, there has been much evidence of a correlation between target attainment or maintenance and better prognosis. In the meantime, researchers are searching for predictors of target attainment. Noteworthy, prospective randomized trials are lacking worldwide to verify the benefits of T2T in various aspects of SLE. The most essential issue is that the optimal definition of the therapeutic target for SLE remains controversial, particularly regarding the maintenance dose of prednisone, the need for immunosuppressive withdrawal, and the requirement for serologic conversion. How to implement T2T principles in clinical practice also needs further investigation.

Phenotype and function of macrophage polarization in monocrotaline-induced pulmonary arterial hypertension rat model.

Pulmonary arterial hypertension (PAH) isa fatal disease characterized by vascular remodeling and chronic inflammation. Macrophages are the key orchestrators of inflammatory and repair responses, and have been demonstrated to be vital in the pathogenesis of PAH. However, specific phenotype of macrophage polarization (M1 & M2 macrophage) in the development of PAH and the underlying mechanisms how they work are still largely unclear. A rat model of monocrotaline (MCT) induced PAH was used. Hemodynamic analysis and histopathological experiments were conducted at day 3, 7, 14, 21 and 28, respectively. In PAH rat lung tissue, confocal microscopic images showed that CD68+NOS2+ M1-like macrophages were remarkably infiltrated on early stage, but dramatically decreased in mid-late stage. Meanwhile, CD68+CD206+ M2-like macrophages in lung tissue accumulated gradually since day 7 to day 28, and the relative ratio of M2/M1 macrophage increased over time. Results detected by western blot and immunohistochemistry were consistent. Further vitro functional studies revealed the possible mechanism involved in this pathophysiological process. By using Transwell co-culture system, it was found that M1 macrophages inducedendothelial cellapoptosis, while M2 macrophages significantly promoted proliferation of both endothelial cell and smooth muscle cell.These data preliminarily demonstrated a temporal dynamic change of macrophage M1/M2 polarization status in the development of experimental PAH. M1 macrophages participated in the initial stage of inflammation by accelerating apoptosis of endothelial cell, while M2 macrophages predominated in the reparative stage of inflammation and the followed stage of aberrant tissue remodeling.

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.

Compromised ultrasound remission, functional ability and clinical decision associated with overlapping Sjögren's syndrome in rheumatoid arthritis patients: results from a propensity-score matched cohort from 2009 to 2019.

OBJECTIVES: Rheumatoid arthritis (RA) patients with Sjögren's syndrome (SS) often present with more severe synovitis. We intended to clarify the impact of overlapping SS on ultrasound remission, functional ability and clinical decision-making in RA patients in a real-world cohort from 2009 to 2019. METHODS: The medical records of RA patients in our medical centre from 2009 to 2019 were reviewed. Cox proportional hazards models of ultrasound remission and no disability (by health assessment questionnaire [HAQ]) were conducted in both the 1-to-1 nearest propensity score matched (PSM) and unmatched cohorts between RA patients with SS (RA-SS) and without (RA-noSS) to correct critical confounders. Four kinds of PSM methods were used and the corresponding average treatment effect on the treated (ATT) was calculated to clarify the effect of overlapping SS on distinguishable characteristics or drug prescription in RA patients. RESULTS: A total of 1100 RA patients were included in the study, of which 133 (12.1%) overlapped with SS. Among 256 patients consisting of 128 RA-SS and 128 RA-noSS after 1-to-1 nearest PSM, overlapping SS was associated with a 44%, 32% lower probability of reaching ultrasound remission, no disability in RA patients, respectively. More hydroxychloroquine (HCQ) usage, less biologic disease-modifying anti-rheumatic drugs (bDMARDs) prescription were confirmed to be correlated with overlapping SS by the robust PSM. CONCLUSIONS: Overlapping SS is associated with a lower probability of reaching ultrasound remission and no disability in RA patients. HCQ may still be the mainstream of clinical decision making in RA-SS patients.

Risk of malignancy with non-TNFi biologic or tofacitinib therapy in rheumatoid arthritis: A meta-analysis of observational studies.

OBJECTIVES: To assess the risk of developing cancer in patients with rheumatoid arthritis (RA) exposed to non-TNF inhibitors (TNFi) biologics or tofacitinib therapy. METHODS: Systematical search of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed. Observational studies that reported cancer incidence in patients with RA treated with biologics or tofacitinib with active comparator of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or TNFi were eligible for inclusion. The pooled relative risk (RR) and 95% confidence interval (CI) were calculated with fix-effects or random-effects model. RESULTS: Of 2,819 identified articles, a total of 10 studies involving over 40,587 patients with more than 87,622 patient-years of exposure to non-TNF inhibitors (TNFi) biologics and 2,221 patients with more than 4,506 patient-years of exposure to tofacitinib were included. Pooled analysis showed there was no increased risk of developing cancer in general or specific cancer types in RA patients receiving treatment with rituximab (pooled RR 0.87, 95% CI 0.74-1.03), tocilizumab (pooled RR 0.92, 95% CI 0.79-1.06), or tofacitinib, compared with those receiving csDMARDs or TNFi. But abatacept was associated with a slightly increased overall cancer risk (pooled RR 1.13, 95% CI 1.02-1.24) and non-melanoma skin cancer (pooled RR 1.26, 95% CI 1.09-1.45), relative to csDMARDs or TNFi in RA patients. CONCLUSION: Among RA patients, a small statistically significant increase in developing cancer was observed for abatacept exposure, while no increased cancer risk for rituximab, tocilizumab or tofacitinib, in comparison with csDMARDs or TNFi.

Overlapping Sjogren's syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019.

BACKGROUND: Overlapping Sjogren's syndrome (SS) is not uncommon in rheumatoid arthritis (RA) and considered as a probable detrimental factor of RA. But data on the impact of overlapping SS on RA therapeutic response is limited. Our current study aimed to identify the effect in a real-world cohort from 2009 to 2019. METHODS: The medical records of RA patients who visited the rheumatology clinic of our medical center from 2009 to 2019 were reviewed. Their composite disease activity scores at each follow-up point were collected. The therapeutic response between RA patients with SS (RA-SS) and without (RA-noSS) was compared. To correct confounders which may affect the therapeutic response, both propensity score matched and unmatched cohorts were analyzed by using the Cox proportional hazards model. RESULTS: Among the 1099 RA patients, 129 (11.7%) overlapped with SS were validated by positive anti-SSA or a minor salivary gland biopsy with histological changes suggestive of SS. After propensity score matching based on their baseline characteristics, 126 of 129 RA-SS and 126 of 970 RA-noSS patients were statistically extracted. Overlapping SS was associated with a 29%, 26%, 18%, and 22% lower probability of reaching remission defined by DAS28-ESR, DAS28-CRP, SDAI, and CDAI in RA patients, respectively. Similar decreased probability of reaching low disease activity was also observed. Although ESR was most significantly affected (HR 0.69, 95% CI 0.61-0.79), other component of composite RA disease activity score was also affected by overlapping SS. Stratification by age, RF/ACPA status, or baseline DAS28-CRP was not associated with change of results. CONCLUSIONS: Overlapping SS is associated with lower probability of reaching remission or low disease activity in RA patients and should be regarded as one of the poor prognostic factors.

Frequencies and predictors of the Lupus Low Disease Activity State and remission in treatment-naïve patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate the attainability of Lupus Low Disease Activity State (LLDAS) and definitions of remission in SLE (DORIS) in a treatment-naïve cohort of SLE. METHODS: LLDAS5 was defined as LLDAS with a prednisone dose ≤5 mg/day. There were four definitions in DORIS: clinical remission on treatment (RONT), complete RONT, clinical remission off treatment (ROFT) and complete ROFT. The treatment-naïve patients from Peking University First Hospital SLE cohort were enrolled. The time to each state and their annual cumulative probabilities were estimated. The frequencies of patients who achieved each component of LLDAS or DORIS during follow-up were determined. The predictors of time to each state were identified. RESULTS: A total of 218 patients were included, with a median follow-up of 4.48 years. Respectively, 190 (87.2%), 160 (73.4%), 148 (67.9%), 94 (43.1%), 23 (10.6%) and 18 (8.3%) patients achieved LLDAS, LLDAS5, clinical RONT, complete RONT, clinical ROFT and complete ROFT. The median time to LLDAS, LLDAS5, clinical RONT and complete RONT were 1.4, 2.3, 2.6 and 4.7 years, respectively. Positive anti-dsDNA, RP and anaemia were significantly associated with prolonged time to LLDAS, LLDAS5 or clinical RONT. CONCLUSION: Our data confirmed that LLDAS is an attainable early treatment target for SLE. Though with more difficulty, RONT can be achieved in two-thirds of our patients. ROFT may not be an ideal treatment target at present as it is only attained in few patients.

Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). METHODS: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. RESULTS: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). CONCLUSION: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.