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.

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.

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.

A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy.

OBJECTIVES: To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies. METHODS: Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI. RESULTS: A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results. CONCLUSION: Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.

The value of 18F-FDG PET/CT in the distinction between retroperitoneal fibrosis and its malignant mimics.

OBJECTIVE: To discuss the utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) in the diagnosis of idiopathic retroperitoneal fibrosis (iRPF). METHODS: IRPF patients diagnosed between September 2011 and June 2016 were included. Retroperitoneal malignancy patients were included as control. The morphological features and FDG uptake of retroperitoneal lesions were measured along with lymph node (LN) mapping. RESULTS: Seventy-one iRPF patients were included. Fifteen lymphoma patients and 6 retroperitoneal metastatic malignancy patients were included as control. Significant differences in morphological features were observed between iRPF and lymphoma but not retroperitoneal metastatic carcinoma. Compared with malignancy, iRPF displayed a lower frequency of high-FDG-uptake retroperitoneal lesions (P = 0.017) and a lower mean maximum standardized uptake value (SUVmax) (P < 0.001). LNs located at axillary, retroperitoneal, supraclavicular, inguinal or peritoneal sites were more frequently observed in retroperitoneal malignancy, therefore, were defined as specific LNs. The area under the curve (AUC) for SUVmax was 0.893 with a sensitivity of 85.7% and a specificity of 80.3%, when the cut-off value of the SUVmax was 6.23. The AUC for the logistic regression model combining the lesions above renal arteries, the SUVmax and the number of specific LNs was 0.987 with a sensitivity of 90.5% and a specificity of 98.6%. The risk stratification model analysis indicated that most of the retroperitoneal malignancy patients were at moderate or high level, while most of the iRPF patients were at low risk. CONCLUSIONS: Retroperitoneal malignancy can mimic iRPF morphologically. 18F-FDG PET/CT can help to distinguish iRPF from retroperitoneal lymphoma and metastatic malignancy.