Tena K. Li

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis

OBJECTIVE To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

High prevalence of asymptomatic vertebral fractures in Chinese women with systemic lupus erythematosus.

Objective. To investigate the prevalence of vertebral fractures and to identify risk factors associated with vertebral fractures in Chinese women with systemic lupus erythematosus (SLE). Methods. One hundred fifty-two consecutive patients with SLE were recruited in this cross-sectional study. Bone mineral density (BMD) measurements of the hip and spine were performed using the same dual energy X-ray absorptiometry (DEXA). Lateral radiographs of the spine (T5–L4) were assessed for vertebral fractures using a method described by Genant. Inflammatory and biochemical markers included C-reactive protein, receptor activator of nuclear factor-κB ligand, serum ß-CrossLaps assay for C-terminal telopeptides of type 1 collagen, and osteoprotegerin (OPG). Results. Asymptomatic vertebral fractures occurred in 20.4% of patients with SLE. Univariate analyses of variables associated with fractures were older age, higher body mass index (BMI), lower BMD spine, lower BMD hips, higher serum C3 and C4, longer estrogen exposure, higher levels of OPG, and the use of sunscreen. Multivariate analysis showed older age (p = 0.017), higher BMI (p < 0.036), and lower BMD of the spine were significantly associated with vertebral fractures in the thoracic and/or lumbar spine (odds ratio 1.068, 1.166, 0.005; p = 0.018, p = 0.025, p = 0.003, respectively). Conclusion. Asymptomatic vertebral fractures occur in 20.4% of patients with SLE and 30% of these patients have normal BMD. The current method using DEXA to predict the presence of vertebral fracture has limited value and there is a need for assessment of bone quality. Vertebral morphometry in patients with SLE is recommended and early therapeutic intervention is necessary to prevent vertebral fractures in patients with SLE.

Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study

BackgroundIn planning a randomized controlled trial of acupuncture, we conducted a pilot study using validated outcome measures to assess the feasibility of the protocol, and to obtain preliminary data on efficacy and tolerability of 3 different forms of acupuncture treatment as an adjunct for the treatment of chronic pain in patients with Rheumatoid arthritis (RA).MethodsThe study employs a randomized, prospective, double-blind, placebo-controlled trial to evaluate the effect of electroacupuncture (EA), traditional Chinese acupuncture (TCA) and sham acupuncture (Sham) in patients with RA. All patients received 20 sessions over a period of 10 weeks. Six acupuncture points were chosen. Primary outcome is the changes in the pain score. Secondary outcomes included the changes in the ACR core disease measures, DAS 28 score and the number of patients who achieved ACR 20 at week 10.ResultsFrom 80 eligible patients, 36 patients with mean age of 58 ± 10 years and disease duration of 9.3 ± 6.4 years were recruited. Twelve patients were randomized to each group. Twelve, 10 and 7 patients from the EA, TCA and Sham group respectively completed the study at 20 weeks (p < 0.03); all except one of the premature dropouts were due to lack of efficacy. At week 10, the pain score remained unchanged in all 3 groups. The number of tender joints was significantly reduced for the EA and TCA groups. Physicians global score was significantly reduced for the EA group and patients global score was significantly reduced for the TCA group. All the outcomes except patients global score remained unchanged in the Sham group.ConclusionThis pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for RA.Trial registrationClinicalTrials.gov NCT00404443

Tumour necrosis factor alpha blockade is associated with sustained regression of carotid intima-media thickness for patients with active psoriatic arthritis: a 2-year pilot study

We have reported that psoriatic arthritis (PsA) patients without overt cardiovascular diseases have evidence of premature atherosclerosis as indicated by an increased carotid intima-media thickness (IMT).1 Whether an increase in IMT reflects current (but reversible) inflammation of the vessel wall rather than more permanent structural vessel changes in PsA has never been assessed. We undertook a prospective, observational study to determine whether a 12-week treatment of tumour necrosis factor alpha (TNFα) blockers may reduce IMT in patients with active PsA, and whether the changes in IMT can be sustained in patients who were continued on long-term TNFα blockers. Twenty consecutive PsA patients with active disease were recruited to receive TNFα blockers. After 12 weeks, nine patients continued (group 1) while 11 patients discontinued TNFα blockers due to financial constraints (group 2). Twenty PsA patients who were naive to TNFα blockers were recruited as controls (group 3). Patients …

Infliximab is associated with improvement in arterial stiffness in patients with early rheumatoid arthritis -- a randomized trial.

Objective. To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). Methods. A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. Results. At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (−0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient’s global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). Conclusion. MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.

Bone Microarchitecture Assessment by High-Resolution Peripheral Quantitative Computed Tomography in Patients with Systemic Lupus Erythematosus Taking Corticosteroids

Objective. We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods. Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy x-ray absorptiometry (DEXA). Results. Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029). Conclusion. Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.

IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: A prospective study

OBJECTIVES To study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in early rheumatoid arthritis (ERA) patients. METHODS A total of 98 ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits. RESULTS Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. Overall, 44(45%), 18(18%), and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean, and simplified disease activity score (SDAI) criteria at 12 months, respectively. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 (P = 0.010) and SDAI remission (P = 0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean, and SDAI remission (P = 0.005, 0.001, and <0.001, respectively). Using multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR = 0.789; P = 0.005) and SDAI remission (0.812; P = 0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients had plaque progression at 12 months. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression respectively (P = 0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors (P = 0.017). CONCLUSIONS Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.

Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High-Resolution Peripheral Quantitative Computed Tomography Study

To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high‐resolution peripheral quantitative computed tomography.

Serum Soluble Receptor for Advanced Glycation End Products Levels and Aortic Augmentation Index in Early Rheumatoid Arthritis—A Prospective Study

OBJECTIVE We assessed whether a serum soluble receptor for advanced glycation end product (sRAGE) levels were associated with a progression of carotid atherosclerosis and arterial stiffness indexes in a cohort of early rheumatoid arthritis (RA) patients. METHODS RA patients with symptoms onset <2 years were recruited. Vascular assessments and serum sRAGE levels were measured at baseline and 1 year later. Arterial stiffness was determined by pulse wave velocity and aortic augmentation index (AIx). Carotid intima-media thickness was measured using high-resolution ultrasound. RESULTS Ninety-four patients completed the 1-year study. Fifty-three (56.4%) achieved disease remission [28-joint disease activity score (DAS28 < 2.6)] at 12 months. Improvement in arterial stiffness was observed as reflected by the significant reductions in AIx and pulse wave velocity. At 12 months, the sRAGE levels increased significantly compared with baseline (939.8 ± 517.7 pg/ml to 1272.1 ± 567.3 pg/ml, P < 0.001). Changes in sRAGE levels were significantly higher in men compared to women (768 ± 510 pg/ml versus 271 ± 490 pg/ml, P < 0.05) and was negatively associated with the change in AIx (r = -0.259, P = 0.023). Changes in sRAGE level were not associated with other demographic, clinical, cardiovascular risk factors or treatment. Using multivariate analysis, the change in sRAGE levels and baseline high-density lipoprotein were independent predictors associated with the change in AIx. CONCLUSIONS Arterial stiffness improved significantly in patients with early RA after effective control of inflammation. Increase in sRAGE level was associated with a decrease in AIx, suggesting that sRAGE may play an important role in the ligand-soluble receptor for advanced glycation end product interaction propagated inflammation and vascular stiffness in these patients.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease

Objectives To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). Methods Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. Results Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). Conclusions Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. Trial registration number NCT02232321.