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1.  Identification of clinical and serological factors during induction treatment of lupus nephritis that are associated with renal outcome 
Lupus Science & Medicine  2015;2(1):e000089.
Objective
To identify factors associated with clinical outcome in patients with lupus nephritis.
Methods
Data from the Aspreva Lupus Management Study (ALMS) were analysed. Using multivariate analysis, we assessed the prognostic value of demographic, clinical, laboratory and histopathological features on the frequency of either complete remission (CR) or treatment failure (TF) during the maintenance phase.
Results
Among the 370 subjects who entered the trial (complete population), non-Hispanic ethnicity was associated with a higher likelihood of CR (OR=2.0). Several factors were independently associated with a greater likelihood of TF, including: (1) anti-double-stranded DNA (anti-dsDNA) at trial entry (OR=12.7), (2) failure to reduce anti-dsDNA within 8 weeks (OR=2.9) and (3) failure to reduce urine protein:creatinine ratio (UP/C) by ≥25% within 8 weeks (OR=2.6). Among the 227 subjects who entered the maintenance phase (maintenance population), baseline estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 was associated with a greater likelihood of CR (OR=2.0), and UP/C >1 at the end of induction was associated with a lower likelihood of CR (OR=0.3). Induction treatment with intravenous cyclophosphamide (IVC) was associated with a lower likelihood of TF (OR=0.5), while lack of treatment with antimalarials (OR=2.4), failure to reduce anti-dsDNA during the first 8 weeks of induction (OR=3.5), failure to reduce UP/C during the first 8 weeks of induction (OR=2.1) and anti-dsDNA positivity at the end of induction (OR=8.3) were independently associated with a greater likelihood of TF.
Conclusions
This analysis demonstrates that levels of anti-dsDNA and UP/C during induction treatment are independently associated with renal outcome over the ensuing 3 years in both the complete and maintenance populations. Ethnicity is associated with renal outcome in just the complete population, and eGFR, induction treatment and treatment with antimalarials are associated with renal outcome in just the maintenance population.
doi:10.1136/lupus-2015-000089
PMCID: PMC4442174  PMID: 26023331
Lupus Nephritis; Autoantibodies; DMARDs (synthetic)
2.  Comparison of Alternative Primary Outcome Measures for Use in Lupus Nephritis Clinical Trials 
Arthritis and rheumatism  2013;65(6):1586-1591.
Objective
Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups.
Methods
Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated.
Results
Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance.
Conclusion
The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens.
doi:10.1002/art.37940
PMCID: PMC4398144  PMID: 23529285
4.  New therapies 
Arthritis Research & Therapy  2012;14(Suppl 3):A4.
doi:10.1186/ar3938
PMCID: PMC3467481
5.  Regulatory T cells as therapeutic targets in rheumatoid arthritis 
Nature reviews. Rheumatology  2009;5(10):560-565.
Regulatory T cells (TREG) are a subset of CD4+ T cells with a critical role in the prevention of autoimmunity. Whether defects in TREG contribute to the pathogenesis of rheumatoid arthritis (RA) is unclear. However, a variety of approved and experimental drugs for RA may work, in part, by promoting the function or increasing numbers of TREG. Furthermore, animal studies demonstrate that direct injection of TREG ameliorates a wide range of experimental models of inflammatory and autoimmune diseases. Thus, cell-based therapy with TREG has the potential to produce durable disease remission in patients with RA.
doi:10.1038/nrrheum.2009.183
PMCID: PMC3086064  PMID: 19798031
6.  A Quality Indicator Set for Systemic Lupus Erythematosus 
Arthritis and rheumatism  2009;61(3):370-377.
Objective
To systematically develop a quality indicator (QI) set for systemic lupus erythematosus (SLE).
Methods
We used a validated process that combined available scientific evidence and expert consensus to develop a QI set for SLE. First, we extracted 20 candidate indicators from a systematic literature review of clinical practice guidelines pertaining to SLE. An advisory panel revised and augmented these candidate indicators, and through two rounds of voting, arrived at 25 QIs. These QIs advanced to the next phase of the project, in which we employed a modification of the RAND/UCLA Appropriateness Method. A systematic review of the literature was performed for each QI, linking the proposed process of care to potential improved health outcomes. After reviewing this scientific evidence, a second interdisciplinary expert panel convened to discuss the evidence and provide final ratings on the validity and feasibility of each QI.
Results
The final expert panel rated 20 QIs as both valid and feasible. Areas covered include diagnosis, general preventive strategies (e.g. vaccinations, sun avoidance counseling, screening for cardiovascular disease), osteoporosis prevention and treatment, drug toxicity monitoring, renal disease, and reproductive health.
Conclusions
We employed a rigorous multi-step approach with systematic literature reviews and two expert panels to develop QIs for SLE. This new set of indicators provides an opportunity to assess health care quality in SLE, and represents an initial step toward the important goal of improving care in this patient population.
doi:10.1002/art.24356
PMCID: PMC2748348  PMID: 19248127
7.  Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study 
Rheumatology (Oxford, England)  2009;49(1):128-140.
Objective. To compare the efficacy and safety of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction treatment for lupus nephritis (LN), by race, ethnicity and geographical region.
Methods. A total of 370 patients with active Class III–V LN received MMF (target dose 3.0 g/day) or IVC (0.5–1.0 g/m2/month), plus tapered prednisone, for 24 weeks. Renal function, global disease activity, immunological complement (C3 and C4) and anti-dsDNA levels are the outcomes that were assessed in this study.
Results. MMF was not superior to IVC as induction treatment (primary objective). There were important pre-specified interactions between treatment and race (P = 0.047) and treatment and region (P = 0.069) (primary endpoint). MMF and IVC response rates were similar for Asians (53.2 vs 63.9%; P = 0.24) and Whites (56.0 vs 54.2%; P = 0.83), but differed in the combined Other and Black group (60.4 vs 38.5%; P = 0.03). Fewer patients in the Black (40 vs 53.9%; P = 0.39) and Hispanic (38.8 vs 60.9%; P = 0.011) groups responded to IVC. Latin American patients had lower response to IVC (32 vs 60.7%; P = 0.003). Baseline disease characteristics were not predictive of response. The incidence of adverse events (AEs) was similar across groups. Serious AEs were slightly more prevalent among Asians.
Conclusions. MMF and IVC have similar efficacy overall to short-term induction therapy for LN. However, race, ethnicity and geographical region may affect treatment response; more Black and Hispanic patients responded to MMF than IVC. As these factors are inter-related, it is difficult to draw firm conclusions about their importance.
Trial registration. National Institutes of Health, www.clinicaltrials.gov, registration number NCT00377637.
doi:10.1093/rheumatology/kep346
PMCID: PMC2789586  PMID: 19933596
Cyclophosphamide; Lupus nephritis; Mycophenolate mofetil; Race; Randomized clinical trial
8.  Strategies for Treating Autoimmune Disease With Monoclonal Antibodies 
Western Journal of Medicine  1985;143(6):804-809.
There is no safe and reliable therapy for most serious autoimmune diseases, such as systemic lupus erythematosus. Severe cases usually require treatment with corticosteroids or cytotoxic drugs or both, which frequently provide inadequate disease control and can cause serious complications. These therapies are not restricted in their effects to cells of the immune system, but rather have a broad range of toxic effects on cells throughout the body. The development of monoclonal antibodies has led to new therapeutic strategies through which treatment can be focused more directly on specific cells (and functions) of the immune system. These strategies have already produced promising results in animal models for several important human autoimmune diseases. We will know soon whether treatment with monoclonal antibodies will be effective in persons with autoimmune disease.
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PMCID: PMC1306490  PMID: 3911593

Results 1-8 (8)