Rheumatology
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Item Open Access Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy(2013) Baraf, Herbert S. B.; Becker, Michael A.; Gutierrez-Urena, Sergio R; Treadwell, Edward L; Vazquez-Mellado, Janitzia; Rehrig, Claudia D; Ottery, Faith D; Sundy, John S; Yood, Robert AINTRODUCTION: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy. METHODS: Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR. RESULTS: Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo). CONCLUSIONS: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.Item Open Access Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees(East Carolina University, 1998-12) Moser, Kathy L.; Neas, Barbara R.; Salmon, Jane E.; Yu, Hua; Gray-McGuire, Courtney; Asundi, Neeraj; Bruner, Gail R.; Fox, Jerome; Kelly, Jennifer; Henshall, Stephanie; Bacino, Debra; Dietz, Myron; Hogue, Robert; Koelsch, Gerald; Nightingale, Lydia; Shaver, Tim; Abdou, Nabih I.; Albert, Daniel A.; Carson, Craig; Petri, Michelle; Treadwell, Edward L.; James, Judith A.; Harley, John B.Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fc! receptors (Fc!R) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, "s >10, purported linkage at 1q41–42, and inbredmouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14–23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26–27, and 12p12–11 in European- Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the Fc!RIIA candidate polymorphism) at 1q23 (lod # 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects. Originally published Proceedings of the National Academy of Sciences, Vol. 95, No. 25, Dec 1998Item Open Access Cardiac tamponade and pericardial disorders in connective tissue diseases: case report and literature review.(East Carolina University, 1994-02) Langley, Ricky L.; Treadwell, Edward L.Pericardial disorders occurring in connective tissue diseases are not uncommon and may present as acute or chronic pericarditis with or without an effusion. In many instances, a diagnosis of pericardial involvement is not found until autopsy. Echocardiography and other currently employed radiographic techniques have enhanced the ability to make a diagnosis. Approximate frequencies of common connective tissue disorders with pericardial involvement include scleroderma (59%), systemic lupus erythematosus (44%), mixed connective tissue disease (30%), rheumatoid arthritis (24%), and polymyositis/dermatomyositis (11%). Cardiac tamponade or constriction is rare. This article describes a patient with clinical features consistent with mixed connective tissue disease that presented with a pericardial effusion and cardiac tamponade. In addition, a review of pericardial involvement in connective tissue diseases and the occurrence of cardiac tamponade or constriction is included. Originally published Journal of the National Medical Association, Vol. 86, No. 2, Feb 1994Item Open Access Thoracolumbar compression fractures presenting with an acute ileus.(East Carolina University, 1990-09) Treadwell, Edward L.; Cunningham, Paul R. G.; Kowalski, Henry M.; Weaver, Michael D.Corticosteroids are commonly used in the treatment of connective tissue diseases such as systemic lupus erythematosus. Although they are usually efficacious, osteoporosis leading to spine compression fractures is not uncommon. In this case report, we describe an elderly patient with systemic lupus erythematosus on long-term corticosteroid therapy who presented with symptoms of acute abdomen with minimal low back symptoms. No intraabdominal process was found by abdominal studies and exploratory laparotomy. Increased lower back symptoms led to further skeletal spine studies, which initially demonstrated a compression fracture at the twelfth thoracic (T12) vertebra. Later, a T8 and a fourth lumbar (L4) compression fracture were also found. Her abdominal and lower back symptoms resolved on conservative therapy. Although the rate of these occurrences are unknown, compression spine fractures should be considered in elderly patients presenting with acute abdomen after being on long-term corticosteroid therapy. Originally published Journal of the National Medical Association, Vol. 82, No. 9, Sep 1990