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| Michelle Petri, M.D.
Treatment Clinical Outcomes | |||||||||||||||
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Abstract 1884 The Impact of In Vivo Anti IL-6 Receptor Blockade on Circulating T and B Cell Subsets in Patients with Systemic Lupus Erythematosus Purpose: This study was the first look at blocking IL-6 in lupus. Study Design: A phase I, open-label study of 14 SLE patients. Tocilizumab was given twice weekly for 12 weeks. Results: There was reduction in acute phase reactants, showing biologic activity of the antibody. Activated CD4+ and CD8+ T-cells decreased. IgD+ CD27- nave B cells increased, and IgD- CD27+ memory cells increased. No lipid side-effects were observed. Editorial Comment: IL-6 may be important in active lupus, as well as contributing to some organ damage, such as osteoporosis. This study could not assess the effect of blocking IL-6 on lupus activity, because of the small numbers, short follow-up, and enrollment of only patients with mild activity. It is a promising first look. Abstract 1959 Confounding by Indication Partially Explains the Protective Effect of Hydroxychloroquine (HCQ) in SLE Survival: Data from a multiethnic U.S. Cohort. Purpose: To determine if hydroxychloroquine improves survival in SLE. Methods: LUMINA is a cohort study involving the University of Alabama, University of Texas at Houston, and Puerto Rico. Thus, it reflects the ethnic diversity of SLE. A propensity score was constructed to determine the probability of prescribing hydroxychloroquine. This term was then included in regression analyses to account for the fact that hydroxychloroquine use might be higher in less severe SLE. Results: When the propensity score was included in the model, hydroxychloroquine use did not significantly protect against mortality (p = 0.0988). Editorial Comment: The use of hydroxychloroquine is SLE has changed from active skin/joint disease to a maintenance drug. Hydroxychloroquines benefits include reduction in flares, reduction in new nephritis, new cognitive impairment, and new thrombosis. The benefit in preventing thrombosis has also been shown in an animal model of antiphospholipid syndrome. Thus, we would expect hydroxychloroquine to have benefit on survival as demonstrated in an earlier study (Lupus 2005;14:220). These authors point out, however, that the earlier analyses were flawed by a bias. Hydroxychloroquine is more often prescribed in milder disease. When a propensity score is used to correct for this bias, hydroxychloroquine is no longer significantly associated with better survival. However, the p-value of 0.0988 still suggests that there may be SOME effect, perhaps demonstrable with a larger sample size. Abstract 1962 The Influence of Treament of Systemic Lupus Erythematosus (sle) with Antimalarials or Azathioprine on the Risk of Thrombosis Purpose: Are antimalarials anti-thrombotic in SLE? Methods: The University of Toronto has one of the largest lupus cohorts. The occurrence of a thrombotic event is recorded. In Cox proportional hazard models, multiple variables including treatment were examined for association with or protection from thrombotic events. Results: 531 SLE patients were followed from inception. 15% had thrombotic events. In univariated analyses, antimalarials were protective (HR 0.68) and azathioprine associated with thrombosis (HR 1.69). In multiple variable models, anti-malarials had a HR of 0.91 (not significant), and azathioprine a HR of 2.08 (statistically significant). Discussion: Antimalarials are anti-thrombotic in animal models of APS and in clinical use after orthopedic surgery. However, in this analysis, no protective effect was found. The use of prophylactic therapy, including aspirin, or statins, in SLE (especially those with antiphospholipid antibodies) may have lessened the chance of finding a protective effect. The azathioprine result is troublesome. No one has previously suggested that azathioprine increases thrombosis. There is no biochemical hypothesis to explain a hypercoagulable effect. It is likely that other co-variates might explain the apparent association. For example, were azathioprine treated patients more likely to be hyperlipidemic, nephrotic, have elevated levels of homocysteine, antiphospholipid positive, or to be sedentary? Did they have more surgical procedures? Did they have more cancers? Before alarm is raised about the use of azathioprine in SLE, the data should be more closely examined. | |||||||||||||||
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Abstract 1958 Mortality in Systemic Lupus Erythematosus: Risk According to Cause, Age, Sex, and Lupus Duration. Purpose: To determine the causes of death in large multi-center SLE cohorts. Methods: SLICC (the Systemic Lupus International Collaborating Clinics) is an international group that recently has addressed the incidence of cancer in SLE. In this study, causes of death were compared with regional or national vital statistics registries. Results: As expected, mortality is increased in SLE (SMR 2.4).
The greatest increase in mortality was in younger patients (< 40 years, the SMR is 10.7) and shorter duration of lupus (< 1 year, the SMR is 5.4). Editorial Comment: Recent attention in SLE has been largely focused on premature atherosclerosis as the major cause of death in SLE. This study draws attention to infection and renal failure as having substantial contributions to mortality, as well. Younger and shorter duration of lupus are the major predictors of death. Urowitz and Gladman had previously reported that early in the course of lupus, deaths are largely from active lupus and infection. Later in the course of lupus, deaths are largely from cardiovascular complications. Lupus patients appear to have particular risk of death with non-Hodgkins lymphoma. A separate abstract suggested that this is because SLE patients are more likely to have poor prognostic subtypes, such as DLBCL. The reason for increased mortality with lung cancer is unclear. However, I sometimes get telephone consults from oncologists that have read that SLE patients may have cutaneous necrosis after radiation. I have always counseled that SLE patients may receive normal radiation doses, but I wonder if some of the increased mortality may reflect a less aggressive regimen in SLE patients. Abstract 1961 Attribution of Neuropsychiatric Events at Diagnosis of Systemic Lupus Erythematosus Purpose: To determine the frequency of neuropsychiatric events in an inception cohort. Methods: This is a multi-center study of the SLICC (Systemic Lupus International Collaborating Clinics) group. Newly diagnosed SLE patients are enrolled, with yearly follow-up using the ACR neuropsychiatric case definitions. Results: 573 patients have been enrolled, one-half are Caucasian. 29% had at least one NP event, with headache, anxiety, and mood disorders most common. Using different rules for attribution, only 18% of NP events could be assigned to SLE itself (affecting 8.6% of the total cohort). Editorial Comment: The current ACR classification criteria for SLE list only psychosis and seizures as neurologic manifestations. This is obviously too restrictive. However, the ACR neuropsychiatric case criteria include many non-specific items (headaches, anxiety, mood disorders). These non-specific items turn out to be very common in SLE patients, but not necessarily more common than controls in other studies. However, even if only 8.6% of SLE patients have neurologic events attributable to lupus, this is still important. We currently have few options in diagnosing neuropsychiatric lupus (brain scan, arteriogram, lumbar puncture, cognitive function tests), few predictors, and few treatments. This inception cohort should provide important information in the future in all of these areas. | |||||||||||||||
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