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Publication
Featured researches published by Brett Jepson.
The New England Journal of Medicine | 2013
Ulrich Specks; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Barri J. Fessler; Linna Ding; L. Viviano; Nadia K. Tchao; Deborah Phippard; Adam Asare; Noha Lim; David Ikle; Brett Jepson; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Coen A. Stegeman; Steven R. Ytterberg; Mark Mueller; Lourdes P. Sejismundo; Kathleen Mieras
BACKGROUND The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown. METHODS In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. RESULTS A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P=0.01) and at 12 months (P=0.009) but not at 18 months (P=0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. CONCLUSIONS In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)
Arthritis & Rheumatism | 2013
Eli M. Miloslavsky; Ulrich Specks; Peter A. Merkel; P. Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cornelis Kallenberg; E W St Clair; Nadia K. Tchao; L. Viviano; Linna Ding; Lourdes P. Sejismundo; Kathleen Mieras; David Ikle; Brett Jepson; Mark Mueller; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Ca Stegeman; Steven R. Ytterberg; John H. Stone
OBJECTIVE To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). METHODS The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegeners Granulomatosis >0, prednisone treatment at any dosage, and other). RESULTS Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare. CONCLUSION Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3-ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.
Journal of The American Society of Nephrology | 2015
Duvuru Geetha; Ulrich Specks; John H. Stone; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Barri J. Fessler; Linna Ding; Nadia K. Tchao; David Ikle; Brett Jepson; Paul Brunetta; Fernando C. Fervenza
Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m(2) × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegeners Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.
Arthritis & Rheumatism | 2014
Eli M. Miloslavsky; Ulrich Specks; Peter A. Merkel; P. Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E W St Clair; Nadia K. Tchao; L. Viviano; Linna Ding; David Ikle; M. Villarreal; Brett Jepson; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Coen A. Stegeman; Steven R. Ytterberg; John H. Stone
Disease relapses are frequent in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re‐treated with rituximab (RTX) and prednisone for severe disease relapses.
Arthritis & Rheumatism | 2014
Eli M. Miloslavsky; U. Specks; Peter A. Merkel; P. Seo; Robert Spiera; Carol A. Langford; Gs Hoffman; Cgm Kallenberg; E W St Clair; Nadia K. Tchao; L. Viviano; Linna Ding; David Ikle; M. Villarreal; Brett Jepson; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Ca Stegeman; Steven R. Ytterberg; John H. Stone
Disease relapses are frequent in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re‐treated with rituximab (RTX) and prednisone for severe disease relapses.
Pediatric Diabetes | 2018
Gordon C. Weir; Mario R. Ehlers; Kristina M. Harris; Sai Kanaparthi; Alice Long; Deborah Phippard; Lia J. Weiner; Brett Jepson; James McNamara; Maria Koulmanda; Terry B. Strom
To determine the safety and pharmacokinetics of alpha‐1 antitrypsin (AAT) in adults and children.
Arthritis & Rheumatism | 2014
Eli M. Miloslavsky; U. Specks; Peter A. Merkel; P. Seo; Robert Spiera; Carol A. Langford; Gs Hoffman; Cornelis Kallenberg; E W St Clair; Nadia K. Tchao; L. Viviano; Linna Ding; David Ikle; M. Villarreal; Brett Jepson; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Ca Stegeman; Steven R. Ytterberg; John H. Stone
Disease relapses are frequent in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re‐treated with rituximab (RTX) and prednisone for severe disease relapses.
Arthritis & Rheumatism | 2011
John H. Stone; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Barri J. Fessler; Nadia K. Tchao; Lisa Webber; Linna Ding; Lourdes P. Sejismundo; Kathleen Mieras; David Ikle; Deborah Phippard; Brett Jepson; Alice Lail; Adam Asare; Noha Lim; Mark Mueller; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina A. Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Coen A. Stegeman
Arthritis & Rheumatism | 2013
Eli M. Miloslavsky; Ulrich Specks; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Nadia K. Tchao; Linna Ding; David Ikle; Brett Jepson; Paul Brunetta; John H. Stone
Arthritis & Rheumatism | 2011
Ulrich Specks; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Swati Tole; Paul Brunetta; Shuyi Shen; Nadia K. Tchao; Barri J. Fessler; Lisa Webber; Linna Ding; Lourdes P. Sejismundo; Kathleen Mieras; Deborah Phippard; Adam Asare; Noha Lim; David Ikle; Brett Jepson; Alice Lail; Mark Mueller