Successful induction of granulomatosis with polyangiitis with tacrolimus

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Abstract

We report a 50-year-old female who presented with inflammatory arthritis, upper respiratory tract symptoms, and microscopic hematuria with nephrotic range proteinuria. Antineutrophil cytoplasmic antibodies (ANCA) were detectable and kidney biopsy showed pauci-immune focal necrotizing crescentic glomerulonephritis. She was treated with pulse intravenous cyclophosphamide (CYC) and prednisolone. Patient developed severe leucopenia after the first dose and subsequently had leucopenia to low dose CYC, mycophenolate mofetil and azathioprine were also tried. However, patient developed leukopenia with all the above agents. Initiation of tacrolimus (TAC) was followed by dramatic response: Proteinuria decreased, serum albumin normalized and C-ANCA and anti-PR3 ANCA assays became negative. This is the first successful case of TAC as an induction agent in a patient with GPA (ANCA associated vasculitis with renal involvement).

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Wegener granulomatosis: an analysis of 158 patients.

Gary Hoffman (1992)

To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. The Warren Magnuson Clinical Center of the National Institutes of Health. Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.

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Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.

, Caroline Savage, Kirsten de Groot … (2009)

Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. 42 centers in 12 European countries. 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. The European Union.

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Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.

D Jayne, O Flossmann, H Raspe … (2008)

We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg-Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74-91%, 45-76% and 60-97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male gender. Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV.

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Author and article information

Journal

Journal ID (nlm-ta): Indian J Nephrol

Journal ID (iso-abbrev): Indian J Nephrol

Journal ID (publisher-id): IJN

Title: Indian Journal of Nephrology

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0971-4065

ISSN (Electronic): 1998-3662

Publication date (Print): Jan-Feb 2015

Volume: 25

Issue: 1

Pages: 46-49

Affiliations

[1]Department of Nephrology, PGIMER, Chandigarh, India

[1 ]Department of Histopathology, St George's Hospital, University of London, London, UK

[2 ]Department of Histopathology, PGIMER, Chandigarh, India

Author notes

Address for correspondence: Dr. Raja Ramachandran, Department of Nephrology, PGIMER, Chandigarh, India. E-mail: drraja_1980@ 123456yahoo.co.in

Article

Publisher ID: IJN-25-46

DOI: 10.4103/0971-4065.136885

PMC ID: 4323912

PubMed ID: 25684872

SO-VID: 2ba215d5-7e6f-45c7-ac0c-4856e3c6af48

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This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Successful induction of granulomatosis with polyangiitis with tacrolimus

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Karger: Nephrology

Most cited references 10

Wegener granulomatosis: an analysis of 158 patients.

Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.

Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.

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