A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester,Minnesota, and Chinese in Singapore,from 1980 to 1992

Objective

To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community‐based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively.

Methods

Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease‐related, and therapy‐related factors.

Results

At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01–9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20–21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07–0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03–0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19–1.15, and RR 0.22, 95% CI 0.05–1.04, respectively).

Conclusion

Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

     

High incidence of potentially virus‐induced malignancies in systemic lupus erythematosus: A long‐term followup study in a Danish cohort

Objective

Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus‐associated malignancies, defined as malignancies potentially caused by virus infection.

Methods

A hospital‐based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.

Results

The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2–2.0). We observed an increased risk of virus‐associated cancers combined (SIR 2.9 [95% CI 2.0–4.1]). Among human papillomavirus (HPV)–associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7–83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3–36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2–2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2–3.6]). Increased SIRs were also found for other potentially virus‐induced cancer types (liver cancer SIR 9.9 [95% CI 2.5–39.8], bladder cancer SIR 3.6 [95% CI 1.4–9.7], and non‐Hodgkin's lymphoma SIR 5.0 [95% CI 1.9–13.3]).

Conclusion

The patients in this SLE cohort experienced an increased risk of HPV‐associated tumors and other potentially virus‐induced cancers during long‐term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.

     

Cigarette smoking and the risk of systemic lupus erythematosus: A meta‐analysis

Objective

Existing studies present conflicting evidence for the role of cigarette smoking as a risk factor in the development of systemic lupus erythematosus (SLE). We performed an extensive search of the medical literature for all studies examining this relationship, and performed a meta‐analysis to arrive at a more precise estimate of effect.

Methods

We performed a computerized literature search for all studies (in all languages), using Medline and EMBASE (1966 to present) and the Cochrane Collaboration database, and completed hand searches of relevant bibliographies and abstracts of conference proceedings. Several investigators systematically extracted data from the relevant studies. Unpublished data were obtained from the author of one abstract. Studies were examined in aggregate for heterogeneity and publication bias. The relationships of current smoking and past smoking (prior to the onset of SLE) to development of SLE were analyzed separately.

Results

Fifty‐two studies were identified and chosen for detailed review. Of these, 9 (7 case–control and 2 cohort studies) were appropriate for inclusion in our meta‐analyses. For current smokers compared with nonsmokers, the odds ratio (OR) for development of SLE was significantly elevated (OR 1.50, 95% confidence interval [95% CI] 1.09–2.08). Former smokers, compared with nonsmokers, did not demonstrate an increased risk of SLE (OR 0.98, 95% CI 0.75–1.27). Several subgroups were also analyzed.

Conclusion

Our meta‐analysis of the 7 existing case–control and 2 cohort studies revealed a small but statistically significant association between current smoking and development of SLE. However, no association between past smoking and development of SLE was observed.

     

Systemic lupus erythematosus in adults is associated with previous Epstein‐Barr virus exposure

Objective

The possible molecular mimicry of the Epstein‐Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B′/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3–1,025, P < 10⁻¹¹). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53–∞, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE.

Methods

We selected 196 antinuclear antibody–positive adult SLE patients (age ≥20 years) and 2 age‐, race‐, and sex‐matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV‐1 and HSV‐2), or varicella‐zoster virus (VZV) by standardized enzyme‐linked immunosorbent assays.

Results

Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45–∞, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV‐2, or VZV.

Conclusion

These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.

     

Treatment of fibromyalgia with cyclobenzaprine: A meta‐analysis

Objective

To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia.

Methods

Articles describing randomized, placebo‐controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted.

Results

Five randomized, placebo‐controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6–5.6) with a pooled risk difference of 0.21 (95% CI 0.09–0.34), which calculates to 4.8 (95% CI 3.0–11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time.

Conclusion

Cyclobenzaprine‐treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

     

Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: A population‐based,case–control study in the Southeastern United States

Objective

Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population‐based study to examine the association between occupational silica exposure and SLE in the southeastern US.

Methods

SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community‐based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency‐matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in‐person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium‐ or high‐level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression.

Results

More patients (19%) than controls (8%) had a history of medium‐ or high‐level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1–4.0], high exposure OR 4.6 [95% CI 1.4–15.4]) that was seen in separate analyses by sex, race, and at different levels of education.

Conclusion

These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment.

     

Mode of delivery in HIV‐infected pregnant women and prevention of mother‐to‐child transmission: changing practices in Western Europe

Objectives

The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother‐to‐child transmission (MTCT).

Methods

The ECS is a cohort study in which HIV‐infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother–child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed.

Results

The elective CS rate increased from 16% in 1985–1993 to 67% in 1999–2001, declining to 51% by 2005–2007. In 2002–2004, 10% of infants were delivered vaginally, increasing to 34% by 2005–2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04–0.12]. The MTCT rate in 2005–2007 was 1%. Among MCPs with maternal HIV RNA<400 HIV‐1 RNA copies/mL (n=960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05–0.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads <50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04–1.29).

Conclusions

Our findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads <50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk–benefit balance of elective CS for women on successful HAART.

     

Cost‐utility and cost‐effectiveness analyses of a long‐term,high‐intensity exercise program compared with conventional physical therapy in patients with rheumatoid arthritis

Objective

To estimate the cost utility and cost effectiveness of long‐term, high‐intensity exercise classes compared with usual care in rheumatoid arthritis (RA) patients.

Methods

RA patients (n = 300) were randomly assigned to either exercise classes or UC; followup lasted for 2 years. Outcome measures were quality‐adjusted life years (QALYs) according to the EuroQol (EQ‐5D), Short Form 6D (SF‐6D), and a transformed visual analog scale (VAS) rating personal health; functional ability according to the Health Assessment Questionnaire (HAQ) and McMaster Toronto Arthritis Patient Preference Interview (MACTAR); and societal costs.

Results

QALYs in both randomization groups were similar according to the EQ‐5D and SF‐6D, but were in favor of usual care according to the VAS (annual difference 0.037 QALY; 95% confidence interval [95% CI] 0.002, 0.069). Functional ability was similar according to the HAQ, but in favor of the exercise classes according to the MACTAR (annual difference 2.9 QALY; 95% CI 0.9, 4.9). Annual medical costs of the exercise program were estimated at €780 per participating patient (€1 ≈ $1.05). The increase per patient in total medical costs of physical therapy was estimated at €430 (95% CI €318, 577), and the increase in total societal costs at €602 (95% CI €?490, 1,664). For societal willingness‐to‐pay equal to €50,000 per QALY, usual care had better cost utility than exercise classes, and significantly so according to the VAS.

Conclusion

From a societal perspective and without taking possible preventive health effects into account, long‐term, high‐intensity exercise classes provide insufficient improvement in the valuation of health to justify the additional costs.

     

Chronic upper extremity pain and co‐occurring symptoms in a general population

Objective

To estimate the prevalence of self reported chronic upper extremity pain associated with physical impairment in a general population, and its co‐occurrence with chronic upper extremity numbness or tingling and chronic pain at other locations.

Methods

A general health questionnaire was mailed to 3,000 persons (age 25–74 years) who were randomly selected from a general population register.

Results

The response rate was 83%. The prevalence of chronic upper extremity pain associated with physical impairment was 20.8% (95% confidence interval [95% CI] 19.2–22.5), and that of co‐occurring numbness or tingling was 6.7% (95% CI 5.7–7.7). Among the responders with chronic upper extremity pain associated with physical impairment, 84% reported more than 1 painful area.

Conclusion

Chronic upper extremity pain associated with physical impairment and co‐occurring chronic upper extremity numbness or tingling were common in the general population. The presence of more than 1 location for pain in the upper extremity as well as in other parts of the body was frequent.

     

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo‐controlled study

Objective

Patients with systemic lupus erythematosus (SLE), with or without end‐stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE.

Methods

Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double‐blind, placebo‐controlled study of the effect of fluvastatin (40–80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5–6‐year trial, and then invited to continue in a 2‐year open‐label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7–8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures.

Results

Fluvastatin reduced low‐density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3–40%), from a mean ± SD of 4.0 ± 0.9 mmoles/liter to 2.8 ± 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7–27.5%), from 6.4 ± 0.9 mmoles/liter to 5.1 ± 1.1 mmoles/liter. Compared with placebo‐treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9–119.4], P = 0.064).

Conclusion

Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

     

Association between physician volume and in‐hospital mortality in patients with systemic lupus erythematosus

Objective

Systemic lupus erythematosus (SLE) is an uncommon, clinically complex disease for which prior experience treating similar patients may be particularly important. This study was undertaken to determine if physician volume is associated with the outcome of hospitalization of patients with SLE.

Methods

Data on in‐hospital mortality in a population‐based sample of 15,509 patients with SLE ages 18 years or older who were hospitalized in 2000, 2001, or 2002 in New York or Pennsylvania were obtained from state health planning agencies. Risks of in‐hospital mortality were examined in relation to the average annual number of patients with SLE hospitalized by the admitting physician.

Results

Physician volume was inversely associated with mortality. Mortality was 4.1% among patients of physicians who treated <1 hospitalized patient with SLE per year, 3.5% among patients of physicians who treated 1–3 patients per year, and 2.5% among patients of physicians who treated >3 patients per year. After adjustment for demographic characteristics, severity of illness, and hospital characteristics, the mortality risk was 20% lower among patients in the middle category of physician volume (odds ratio 0.80, 95% confidence interval 0.66–0.96, P =0.02), and 42% lower among patients in the highest category of physician volume (odds ratio 0.58, 95% confidence interval 0.42–0.82, P = 0.002), compared with patients in the lowest category. The association was stronger among patients with nephritis (n = 2,673), for whom the adjusted odds of mortality were ∼60% lower among those in the highest category of physician volume.

Conclusion

Our findings indicate that higher disease‐specific physician volume is associated with lower risks of in‐hospital mortality in patients with SLE.

     

Role of the Fcγ receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: A meta‐analysis

Objective

To assess the impact of the Fcγ receptor type IIa (FcγRIIa)–R/H131 polymorphism on the risk for systemic lupus erythematosus (SLE) and development of lupus nephritis.

Methods

A meta‐analysis was performed based on the Medline and Embase databases (last retrieval August 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators.

Results

A total of 25 comparisons from 17 studies involving R/H131 genotyping of 1,405 patients with lupus nephritis, 1,709 SLE patients without nephritis, and 2,580 non‐SLE controls were included. No association between RR genotype and risk of lupus nephritis relative to both other genotypes (odds ratio [OR] 1.05, 95% confidence interval [95% CI] 0.88–1.27) was demonstrated in the total meta‐analysis or in any racial subgroup. The RR genotype was more frequent in SLE patients as a whole (OR 1.30, 95% CI 1.10–1.52) and in SLE patients without nephritis (OR 1.27, 95% CI 1.04–1.55) compared with disease‐free controls. A potential dose–response relation between the R131 allele and the risk of SLE was also identified, with an OR of 1.23 for RR versus RH (95% CI 1.03–1.46). The OR was 1.55 for RR versus HH (95% CI 1.21–1.98). There was no significant heterogeneity between racial subgroups. The population‐attributable fractions of SLE cases due to the FcγRIIa‐R131 allele were 13%, 40%, and 24% in subjects of European, African, and Asian descent, respectively.

Conclusion

The FcγRIIa‐R/H131 polymorphism represents a significant risk factor for SLE but has no clear effect on susceptibility for lupus nephritis.

     

Responsiveness of self‐report and therapist‐rated upper extremity structural impairment and functional outcome measures in early rheumatoid arthritis

Objective

To provide a responsiveness analysis of the self‐report and therapist‐rated upper extremity functional outcome measures used in a rehabilitation trial.

Methods

A variety of commonly used therapist‐assessed and self‐report structural impairment and functional outcome measures were compared for the ability to detect and measure change in wrist and hand status in an early rheumatoid arthritis population over 12 months. Responsiveness was measured using the standardized response mean (SRM) and effect size (ES).

Results

The most responsive measures were the Michigan Hand Outcomes Questionnaire (SRM 0.49 [95% confidence interval (95% CI) 0.27, 0.72], ES = 0.37 [95% CI 0.21, 0.54]), dominant metacarpophalangeal joint ulnar deviation (SRM 0.46 [95% CI 0.27, 0.65], ES = 0.58 [95% CI 0.34, 0.82]), and mean power handgrip test (SRM 0.45 [95% CI 0.26, 0.64], ES = 0.32 [95% CI 0.18, 0.45]) The least responsive measure was the Health Assessment Questionnaire (SRM ?0.12 [95% CI ?0.31, 0.08], ES = ?0.08 [95% CI ?0.21, 0.05]).

Conclusion

Over 12 months, there was substantial variation in wrist and hand outcome measures to detect change over time in an early RA population. Careful consideration is required to choose the most appropriate measure that can detect change.

     

The −169C/T polymorphism in FCRL3 is not associated with susceptibility to rheumatoid arthritis or systemic lupus erythematosus in a case–control study of Koreans

Objective

In Japanese individuals, the −169C/T single‐nucleotide polymorphism (SNP) in FCRL3 has been reported to be associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroid diseases. The objective of this study was to test the association of this SNP with RA and SLE, in a case–control study of Korean individuals.

Methods

The −169C/T SNP in FCRL3 was genotyped in 1,060 patients with RA, 457 patients with SLE, and 697 unaffected control subjects, using the MassARRAY SNP genotyping system. Associations were tested by multivariate logistic regression, with adjustments for age and sex.

Results

No association was detected between the −169C/T SNP and RA (odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.83–1.48, P = 0.50) or SLE (OR 1.00, 95% CI 0.73–1.37, P = 0.99). This SNP was not associated with rheumatoid factor status, shared epitope status, radiographic severity in patients with RA, or disease manifestations in patients with SLE.

Conclusion

The association of the −169C/T SNP in FCRL3 with RA and SLE that was observed in Japanese patients was not replicated in a Korean population.

     

Relationship between anti–double‐stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

Objective

To examine the relationship between changes in anti–double‐stranded DNA (anti‐dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.

Methods

Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti‐dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA‐based bioconjugate (abetimus sodium; LJP 394) was used.

Results

Changes in anti‐dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti‐dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti‐dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26–68%, nominal P = 0.0007) and a 53% reduction (95% CI 33–69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti‐dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).

Conclusion

Changes in anti‐dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti‐dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

     

The prevalence and incidence of biopsy‐proven lupus nephritis in the UK: Evidence of an ethnic gradient

Objective

Renal involvement is a major complication of systemic lupus erythematosus (SLE) and is a strong determinant of morbidity and mortality. There have been no previous studies of the epidemiology of lupus nephritis. Our aim was to establish the prevalence and incidence of biopsy‐proven lupus nephritis in the northwest of England in 2001 and to examine the influence of age, sex, and ethnicity.

Methods

Adults (age 18 years and older) with biopsy‐proven lupus nephritis were identified from 5 sources: renal biopsy databases, dialysis/transplant databases, nephrologists' patients, clinic lists, and lupus patient groups. The denominator data for the northwest of England were ascertained from the 2001 census.

Results

We identified 208 cases of biopsy‐proven lupus nephritis (176 women, 32 men): the overall prevalence was 4.4 per 100,000 population (95% confidence interval [95% CI] 3.8–5.0), 7.1 per 100,000 (95% CI 6.1–8.2) in women, and 1.4 per 100,000 (95% CI 1.0–2.0) in men. The prevalence was significantly higher among women in the ethnic subgroups: 110.3 per 100,000 population (95% CI 55.0–197.3) in Chinese patients, 99.2 per 100,000 (95% CI 55.5–163.6) in Afro‐Caribbean, 21.4 per 100,000 (95% CI 12.0–35.2) in Indo‐Asian (Asians from the Indian subcontinent), and 5.6 per 100,000 (95% CI 4.7–6.7) in white patients. The overall annual incidence rate was 0.40 per 100,000 population per year (95% CI 0.24–0.63), with a rate of 0.68 (95% CI 0.40–1.10) in women and 0.09 (95% CI 0.01–0.32) in men. Capture–recapture methods did not suggest any additional cases.

Conclusion

This first estimate of the prevalence and incidence of biopsy‐proven lupus nephritis demonstrates dramatic differences in prevalence according to ethnicity, with an increasing gradient from the white to the Indo‐Asian, Afro‐Caribbean, and Chinese populations.

     

Association of a transmembrane polymorphism of Fcγ receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients

Objective

To investigate the possible association of the Fcγ receptor IIb (FcγRIIb) Ile/Thr187 transmembrane domain polymorphism, which significantly affects receptor signaling, with susceptibility to systemic lupus erythematosus (SLE) in Taiwanese patients.

Methods

We used matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry to genotype 351 Taiwanese SLE patients and 372 age‐ and sex‐matched healthy individuals from the same geographic area. Allele frequencies and genotype distributions were compared between the patients and controls, both as an aggregate and as stratified by sex, autoantibody profile, and clinical parameters. A combined analysis was conducted to assess the FCGR2B Thr187 allele as a common risk factor in different ethnic populations.

Results

The minor Thr187 allele was significantly associated with SLE in Taiwanese subjects (P = 0.017, odds ratio [OR] 1.989 [95% confidence interval (95% CI) 1.119–3.553]). Interestingly, male SLE patients showed enrichment of the Thr/Thr187 genotype (24%; 7 of 29) as compared with female SLE patients (10%; 32 of 322) (P = 0.043, OR 2.884 [95% CI 1.028–7.839]). Additionally, SLE patients with Thr/Thr187 and Ile/Thr187 genotypes were more likely to have pleural effusions (P = 0.038, OR 1.874 [95% CI 1.033–3.411]) and anti‐SSA/Ro antibody production (P = 0.046, OR 2.221 [95% CI 1.013–4.897]). Combined analysis of 4 groups of Asian patients strongly supported the association of the FCGR2B Thr187 allele with the lupus phenotype (P = 0.000159).

Conclusion

The FcγRIIb transmembrane polymorphism is a strong disease susceptibility candidate in epistasis with other genetic effects in Taiwanese and other Asian populations. It may also play a more prominent role in male patients with SLE.

     

The efficacy and safety of abatacept in patients with non–life‐threatening manifestations of systemic lupus erythematosus: Results of a twelve‐month,multicenter, exploratory,phase IIb,randomized, double‐blind,placebo‐controlled trial

Objective

To evaluate abatacept therapy in patients with non–life‐threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.

Methods

In a 12‐month, multicenter, exploratory, phase IIb randomized, double‐blind, placebo‐controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (∼10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper.

Results

A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference −3.5 [95% CI −15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept‐treated and placebo‐treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician‐assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient‐reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease‐related events occurring during the first 6 months of the study (including the steroid taper period).

Conclusion

Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non–life‐threatening manifestations of SLE. The increased rate of SAEs requires further assessment.

     

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

Objective

To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort.

Methods

Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser).

Results

Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6–98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6–11 months, 146 (12.8%) for 1–2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person‐months of followup) were 3.85 (95% confidence interval [95% CI] 1.41–8.37), 2.7 (95% CI 1.41–4.76), and 0.54 (95% CI 0.37–0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18–4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39–0.99).

Conclusion

Antimalarial drugs were shown to have a protective effect, possibly in a time‐dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.